431 results on '"Drenth JP"'
Search Results
2. Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome
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Van Der Hilst, Jc, Bodar, Ec, Barron, Ks, Frenkel, J., Drenth, Jp, Van Der Meer, Jw, Simon, A., Hids Study Group, International, Other departments, General Internal Medicine, Institut de génétique humaine (IGH), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
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Male ,MEVALONATE KINASE-DEFICIENCY ,Pediatrics ,Abdominal pain ,Gastrointestinal Diseases ,Familial Mediterranean fever ,Membrane transport and intracellular motility [NCMLS 5] ,SYNDROME HIDS ,Receptors, Tumor Necrosis Factor ,Etanercept ,Cohort Studies ,0302 clinical medicine ,Quality of life ,Prednisone ,Medicine ,030212 general & internal medicine ,Longitudinal Studies ,Young adult ,Child ,ComputingMilieux_MISCELLANEOUS ,HEALTH-STATUS ,General Medicine ,Syndrome ,Middle Aged ,Arthralgia ,3. Good health ,Pathogenesis and modulation of inflammation [N4i 1] ,Phosphotransferases (Alcohol Group Acceptor) ,Antirheumatic Agents ,Child, Preschool ,Disease Progression ,Female ,medicine.symptom ,Periodic fever syndrome ,Infection and autoimmunity [NCMLS 1] ,FAMILIAL MEDITERRANEAN FEVER ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Skin Diseases ,Invasive mycoses and compromised host [N4i 2] ,03 medical and health sciences ,Young Adult ,DIAGNOSTIC-VALUE ,Humans ,HYPER-IGD SYNDROME ,Molecular gastro-enterology and hepatology [IGMD 2] ,INTERLEUKIN-1-BETA SECRETION ,Lymphatic Diseases ,Aged ,030203 arthritis & rheumatology ,SPECTRUM ,MUTATIONS ,business.industry ,Hyper-IgD syndrome ,medicine.disease ,Health Surveys ,Interleukin-1 beta secretion ,Surgery ,Interleukin 1 Receptor Antagonist Protein ,PERIODIC FEVER SYNDROME ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Genetic defects of metabolism [UMCN 5.1] ,Immunoglobulin G ,Mutation ,Splenomegaly ,Quality of Life ,Microbial pathogenesis and host defense [UMCN 4.1] ,Mevalonate Kinase Deficiency ,business - Abstract
Contains fulltext : 69054.pdf (Publisher’s version ) (Open Access) The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS), one of the autoinflammatory syndromes, is caused by mutations in the gene coding for mevalonate kinase (MVK). We conducted the current study to assess the genetic, laboratory, and clinical features as well as the complications and course of disease in patients with genetically confirmed HIDS. In addition, we studied the quality of life and course of life in a selection of patients. Follow-up data were obtained by a questionnaire sent to all physicians of patients in the International HIDS Database. In addition, we assessed the course of life and quality of life in Dutch patients aged >16 years using validated quality of life instruments. Data were obtained from 103 patients from 18 different countries. The median age of first attack was 6 months (range, 0-120 mo), with a median period of 9.9 years from onset of disease to diagnosis. The most frequent symptoms that accompanied attacks of fever were lymphadenopathy, abdominal pain, arthralgia, diarrhea, vomiting, skin lesions, and aphthous ulcers. Amyloidosis was a severe but infrequent complication (2.9%). The median serum IgD level was 400 U/mL. IgD levels were normal in 22% of patients. The 4 most prevalent mutations (V377I, I268T, H20P/N, P167L) accounted for 71.5% of mutations found. The frequency of attacks decreased with the patient's increasing age, although 50% of patients over the age of 20 years still had 6 or more attacks per year. Many drugs have been tried in HIDS. Some patients responded to high-dose prednisone (24.4% response). Anakinra and etanercept can also be effective (33.3% response). Quality of life was determined in a subgroup of patients (n = 28). Social functioning, general health perception, and vitality were significantly lower in patients with HIDS than in controls, as were autonomy and social development. In addition, HIDS had an adverse impact on educational achievements and employment status. In conclusion, HIDS is an early-onset disease that is accompanied by an array of inflammatory symptoms. Although the frequency of attacks decreases during the patient's life, many patients continue to have frequent attacks. HIDS impairs several aspects of quality of life.
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- 2008
3. Verapamil-induced secondary erythermalgia
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Jan Jacques Michiels, Drenth Jp, Vojislav D. Vuzevski, and T. Van Joost
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Male ,medicine.medical_specialty ,Erythema ,medicine.medical_treatment ,Dermatology ,Erythromelalgia ,medicine ,Humans ,Burning Pain ,Skin ,Chemotherapy ,Aspirin ,business.industry ,Vascular disease ,Foot ,Middle Aged ,medicine.disease ,Surgery ,Verapamil ,Anesthesia ,Histopathology ,medicine.symptom ,business ,medicine.drug - Abstract
A 59-year-old man developed red, swollen and warm feet accompanied by intermittent burning pain during treatment for cardiac failure and arrhythmias with several drugs including verapamil. The condition gradually worsened until there was persistent disabling burning pain and severe erythema and swelling of the feet. Aspirin and other analgesics were ineffective in relieving the discomfort. Histopathology of punch biopsies showed a mild perivascular mononuclear infiltrate and moderate perivascular oedema. Within 2 weeks of stopping verapamil the burning pain, erythema, and swelling of the feet had resolved. The clinical features and subsequent course are consistent with a diagnosis of erythermalgia secondary to verapamil.
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- 1992
4. Die Rolle des EPHX1 Polymorphismus Y113H bei Pankreaserkrankungen
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Ockenga, J, primary, Strunck, S, additional, Post, C, additional, Schulz, HU, additional, Pfützer, R, additional, Löhr, M, additional, Oettle, H, additional, Rosendahl, J, additional, Keim, V, additional, Drenth, JP, additional, Jansen, JB, additional, Lochs, H, additional, and Witt, H, additional
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- 2006
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5. CONFERENCE
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Powell Rj and Drenth Jp
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business.industry ,Medicine ,General Medicine ,business - Published
- 1995
6. Substance P is not involved in primary and secondary erythermalgia.
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Drenth, JP, primary, Michiels, JJ, additional, and Van Joost, T., additional
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- 1997
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7. Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome
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Drenth, JP, primary, van Deuren, M, additional, van der Ven-Jongekrijg, J, additional, Schalkwijk, CG, additional, and van der Meer, JW, additional
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- 1995
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8. Nav1.7-related small fiber neuropathy: Impaired slow-inactivation and DRG neuron hyperexcitability.
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Han C, Hoeijmakers JG, Ahn HS, Zhao P, Shah P, Lauria G, Gerrits MM, Te Morsche RH, Dib-Hajj SD, Drenth JP, Faber CG, Merkies IS, and Waxman SG
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- 2012
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9. Gain of function Na(V) 1.7 mutations in idiopathic small fiber neuropathy.
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Faber CG, Hoeijmakers JG, Ahn HS, Cheng X, Han C, Choi JS, Estacion M, Lauria G, Vanhoutte EK, Gerrits MM, Dib-Hajj S, Drenth JP, Waxman SG, and Merkies IS
- Abstract
OBJECTIVE: Small nerve fiber neuropathy (SFN) often occurs without apparent cause, but no systematic genetic studies have been performed in patients with idiopathic SFN (I-SFN). We sought to identify a genetic basis for I-SFN by screening patients with biopsy-confirmed idiopathic SFN for mutations in the SCN9A gene, encoding voltage-gated sodium channel Na(V) 1.7, which is preferentially expressed in small diameter peripheral axons. METHODS: Patients referred with possible I-SFN, who met the criteria of >=2 SFN-related symptoms, normal strength, tendon reflexes, vibration sense, and nerve conduction studies, and reduced intraepidermal nerve fiber density (IENFD) plus abnormal quantitative sensory testing (QST) and no underlying etiology for SFN, were assessed clinically and by screening of SCN9A for mutations and functional analyses. RESULTS: Twenty-eight patients who met stringent criteria for I-SFN including abnormal IENFD and QST underwent SCN9A gene analyses. Of these 28 patients with biopsy-confirmed I-SFN, 8 were found to carry novel mutations in SCN9A. Functional analysis revealed multiple gain of function changes in the mutant channels; each of the mutations rendered dorsal root ganglion neurons hyperexcitable. INTERPRETATION: We show for the first time that gain of function mutations in sodium channel Na(V) 1.7, which render dorsal root ganglion neurons hyperexcitable, are present in a substantial proportion (28.6%; 8 of 28) of patients meeting strict criteria for I-SFN. These results point to a broader role of Na(V) 1.7 mutations in neurological disease than previously considered from studies on rare genetic syndromes, and suggest an etiological basis for I-SFN, whereby expression of gain of function mutant sodium channels in small diameter peripheral axons may cause these fibers to degenerate. ANN NEUROL 2012;71:26-39. [ABSTRACT FROM AUTHOR]
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- 2012
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10. Influence of alpha-1 antitrypsin heterozygosity on treatment efficacy of HCV combination therapy.
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Kok KF, van Soest H, van Herwaarden AE, van Oijen MG, Boland GJ, Halangk J, Berg T, de Vries RA, Drenth JP, Kok, Karin F, van Soest, Hanneke, van Herwaarden, Antonius E, van Oijen, Martijn G H, Boland, Greet J, Halangk, Juliane, Berg, Thomas, de Vries, Richard A, and Drenth, Joost P H
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- 2010
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11. Do COX-2 inhibitors give enough gastrointestinal protection?
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Drenth JP and Verheugt FW
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- 2007
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12. A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis
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Heiko, Witt, Miklos Sahin Toth, Olfert, Landt, Jian Min Chen, Thilo, Kahne, Drenth, Joost P. H., Zoltan, Kukor, Edit, Szepessy, Walter, Halangk, Stefan, Dahm, Klaus, Rohde, Hans Ulrich Schulz, Cedric Le Marechal, Nejat, Akar, Ammann, Rudolf W., Kaspar, Truninger, Mario, Bargetzi, Eesh, Bhatia, Carlo, Castellani, Giulia Martina Cavestro, Milos, Cerny, DESTRO-BISOL, Giovanni, Spedini, Gabriella, Hans, Eiberg, Jansen, Jan B. M. J., Monika, Koudova, Eva, Rausova, Milan, Macek, Macek Jr, M., Nuria, Malats, Real, Francisco X., Hans Jurgen Menzel, Pedro, Moral, Roberta, Galavotti, Pier Franco Pignatti, Olga, Rickards, Julius, Spicak, Narcis Octavian Zarnescu, Wolfgang, Bock, Gress, Thomas M., Helmut, Friess, Johann, Ockenga, Hartmut, Schmidt, Roland, Pfutzer, Matthias, Lohr, Peter, Simon, Frank Ulrich Weiss, Lerch, Markus M., Niels, Teich, Volker, Keim, Thomas, Berg, Bertram, Wiedenmann, Werner, Luck, David Alexander Groneberg, Michael, Becker, Thomas, Keil, Andreas, Kage, Jana, Bernardova, Markus, Braun, Claudia, Guldner, Juliane, Halangk, Jonas, Rosendahl, Ulrike, Witt, Matthias, Treiber, Renate, Nickel, Claude, Ferec, Witt, H, SAHIN TOTH, M, Landt, O, Chen, Jm, Kahne, T, Drenth, Jp, Kukor, Z, Szepessy, E, Halangk, W, Dahm, S, Rohde, K, Schulz, Hu, LE MARECHAL, C, Akar, N, Ammann, Rw, Truninger, K, Bargetzi, M, Bhatia, E, Castellani, C, Cavestro, GIULIA MARTINA, Cerny, M, DESTRO BISOL, G, Spedini, G, Eiberg, H, Jansen, Jb, Koudova, M, Rausova, E, MACEK M., Jr, Malats, N, Real, Fx, Menzel, Hj, Moral, P, Galavotti, R, Pignatti, Pf, Rickards, O, Spicak, J, Zarnescu, No, Bock, W, Gress, Tm, Friess, H, Ockenga, J, Schmidt, H, Pfutzer, R, Lohr, M, Simon, P, Weiss, Fu, Lerch, Mm, Teich, N, Keim, V, Berg, T, Wiedenmann, B, Luck, W, Groneberg, Da, Becker, M, Keil, T, Kage, A, Bernardova, J, Braun, M, Guldner, C, Halangk, J, Rosendahl, J, Witt, U, Treiber, M, Nickel, R, and Ferec, C.
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trypsin inhibitor ,Models, Molecular ,Enteropeptidase ,Pancreatic disease ,Membrane transport and intracellular motility [NCMLS 5] ,arginine ,genetic risk ,chemistry.chemical_compound ,Models ,proteinosis ,Trypsin ,Pancreatic Secretory Trypsin Inhibitor ,PRSS1 gene ,enteropeptidase ,medicine.diagnostic_test ,adult ,Hydrolysis ,cationic trypsinogen ,protection ,unclassified drug ,enzyme activity ,female ,priority journal ,risk factor ,CHRONIC PANCREATITIS ,protein degradation ,Trypsinogen ,medicine.drug ,medicine.medical_specialty ,anionic trypsinogen ,Proteolysis ,Biology ,Article ,male ,Internal medicine ,Genetics ,medicine ,Matrix-Assisted Laser Desorption-Ionization ,Humans ,PRSS2 ,controlled study ,human ,Molecular gastro-enterology and hepatology [IGMD 2] ,gene ,DNA Primers ,Genetic polymorphism ,catalysis ,Base Sequence ,Spectrometry ,disease predisposition ,Molecular ,cationic trypsinogen prss1 ,glycine ,pancreatic secretory trypsin inhibitor spink1 ,trypsin ,trypsinogen ,article ,chronic pancreatitis ,codon ,genetic susceptibility ,major clinical study ,nucleotide sequence ,Chronic Disease ,Haplotypes ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Mass ,medicine.disease ,Tripsinogen ,Tripsina ,Settore BIO/18 - Genetica ,Endocrinology ,Genetic defects of metabolism [UMCN 5.1] ,Pancreatitis ,chemistry ,Genètica - Abstract
Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis. The initial experiments were supported by the DFG (Wi 2036/1-1). This work was supported by the Sonnenfeld-Stiftung, Berlin, Germany (to H.W.), the US National Institutes of Health (NIH) (grant DK058088 to M.S.-T.), INSERM (Institut National de la Santé et de la Recherche Médicale) and the Programme Hospitalier de Recherche Clinique (grant PHRC R 08-04 to C.F.)
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- 2006
13. A TGFβ-ECM-integrin signaling axis drives structural reconfiguration of the bile duct to promote polycystic liver disease.
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Waddell SH, Yao Y, Olaizola P, Walker A, Jarman EJ, Gournopanos K, Gradinaru A, Christodoulou E, Gautier P, Boerrigter MM, Cadamuro M, Fabris L, Drenth JP, Kendall TJ, Banales JM, Khamseh A, Mill P, and Boulter L
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- Humans, Extracellular Matrix, Integrins, Bile Ducts, Cysts
- Abstract
The formation of multiple cysts in the liver occurs in a number of isolated monogenic diseases or multisystemic syndromes, during which bile ducts develop into fluid-filled biliary cysts. For patients with polycystic liver disease (PCLD), nonsurgical treatments are limited, and managing life-long abdominal swelling, pain, and increasing risk of cyst rupture and infection is common. We demonstrate here that loss of the primary cilium on postnatal biliary epithelial cells (via the deletion of the cilia gene Wdr35 ) drives ongoing pathological remodeling of the biliary tree, resulting in progressive cyst formation and growth. The development of cystic tissue requires the activation of transforming growth factor-β (TGFβ) signaling, which promotes the expression of a procystic, fibronectin-rich extracellular matrix and which itself is perceived by a changing profile of integrin receptors on the cystic epithelium. This signaling axis is conserved in liver cysts from patients with either autosomal dominant polycystic kidney disease or autosomal dominant polycystic liver disease, indicating that there are common cellular mechanisms for liver cyst growth regardless of the underlying genetic cause. Cyst number and size can be reduced by inhibiting TGFβ signaling or integrin signaling in vivo. We suggest that our findings represent a therapeutic route for patients with polycystic liver disease, most of whom would not be amenable to surgery.
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- 2023
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14. Disease burden in primary sclerosing cholangitis in the Netherlands: A long-term follow-up study.
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van Munster KN, Mol B, Goet JC, van Munster SN, Weersma RK, de Vries AC, van der Meer AJ, Inderson A, Drenth JP, van Erpecum KJ, Boonstra K, Beuers U, Dijkgraaf MGW, and Ponsioen CY
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- Humans, Follow-Up Studies, Quality of Life, Netherlands, Cost of Illness, Cholangitis, Sclerosing
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Background & Aims: Primary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease which greatly impacts the lives of individuals. Burden of disease due to shortened life expectancy and impaired quality of life is ill-described. The aim of this study was to assess long-term disease burden in a large population-based registry with regard to survival, clinical course, quality adjusted life years (QALYs), medical consumption and work productivity loss., Methods: All PSC patients living in a geographically defined area covering ~50% of the Netherlands were included, together with patients from the three liver transplant centres. Survival was estimated by competing risk analysis. Proportional shortfall of QALYs during disease course was measured relative to a matched reference cohort using validated questionnaires. Work productivity loss and medical consumption were evaluated over time., Results: A total of 1208 patients were included with a median follow-up of 11.2 year. Median liver transplant-free survival was 21.0 years. Proportional shortfall of QALYs increased to 48% >25 years after diagnosis. Patients had on average 12.4 hospital contact days among which 3.17 admission days per year, annual medical costs were €12 169 and mean work productivity loss was 25%., Conclusions: Our data quantify for the first time disease burden in terms of QALYs lost, clinical events, medical consumption, costs as well as work productivity loss, and show that all these are substantial and increase over time., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)
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- 2023
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15. A limited role of cytokine storm and fibrogenesis in COVID-19 related liver injury.
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Westerouen van Meeteren MJ, Van den Heuvel FM, Weijers G, Joosten LA, De Mast Q, Van de Veerdonk FL, Pickkers P, De Nooijer AH, Hoefsloot W, Drenth JP, De Korte CL, Nijveldt R, Netea MG, and Tjwa ET
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- Adult, Aged, Biomarkers blood, COVID-19 complications, COVID-19 diagnosis, Cytokine Release Syndrome blood, Cytokine Release Syndrome diagnosis, Cytokine Release Syndrome pathology, Elasticity Imaging Techniques, Female, Humans, Liver Cirrhosis diagnosis, Liver Cirrhosis immunology, Liver Cirrhosis pathology, Male, Middle Aged, COVID-19 immunology, COVID-19 pathology, Cytokine Release Syndrome virology, Liver Cirrhosis virology
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- 2021
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16. The UEG Journal is steaming ahead.
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Drenth JP and Lerch MM
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- Editorial Policies, Europe, Gastroenterology organization & administration, History, 21st Century, International Cooperation, Open Access Publishing history, Open Access Publishing trends, Gastroenterology methods, Open Access Publishing organization & administration
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- 2020
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17. Analysis of GPRC6A variants in different pancreatitis etiologies.
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Kaune T, Ruffert C, Hesselbarth N, Damm M, Krug S, Cardinal von Widdern J, Masson E, Chen JM, Rebours V, Buscail L, Férec C, Grützmann R, Te Morsche RHM, Drenth JP, Cavestro GM, Zuppardo RA, Saftoiu A, Malecka-Panas E, Głuszek S, Bugert P, Lerch MM, Sendler M, Weiss FU, Zou WB, Deng SJ, Liao Z, Scholz M, Kirsten H, Hegyi P, Witt H, Michl P, Griesmann H, and Rosendahl J
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- Adult, Aged, Asian People, DNA genetics, Europe, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Pancreatitis, Alcoholic genetics, Polymorphism, Single Nucleotide, Receptors, Calcium-Sensing genetics, Risk Factors, Signal Transduction genetics, White People, Pancreatitis genetics, Receptors, G-Protein-Coupled genetics
- Abstract
Background: The G-protein-coupled receptor Class C Group 6 Member A (GPRC6A) is activated by multiple ligands and is important for the regulation of calcium homeostasis. Extracellular calcium is capable to increase NLRP3 inflammasome activity of the innate immune system and deletion of this proinflammatory pathway mitigated pancreatitis severity in vivo. As such this pathway and the GPRC6A receptor is a reasonable candidate gene for pancreatitis. Here we investigated the prevalence of sequence variants in the GPRC6A locus in different pancreatitis aetiologies., Methods: We selected 6 tagging SNPs with the SNPinfo LD TAG SNP Selection tool and the functional relevant SNP rs6907580 for genotyping. Cohorts from Germany, further European countries and China with up to 1,124 patients and 1,999 controls were screened for single SNPs with melting curve analysis., Results: We identified an association of rs1606365(G) with alcoholic chronic pancreatitis in a German (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.65-0.89, p = 8 × 10
-5 ) and a Chinese cohort (OR 0.78, 95% CI 0.64-0.96, p = 0.02). However, this association was not replicated in a combined cohort of European patients (OR 1.18, 95% CI 0.99-1.41, p = 0.07). Finally, no association was found with acute and non-alcoholic chronic pancreatitis., Conclusions: Our results support a potential role of calcium sensing receptors and inflammasome activation in alcoholic chronic pancreatitis development. As the functional consequence of the associated variant is unclear, further investigations might elucidate the relevant mechanisms., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)- Published
- 2020
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18. UEG Guidelines framework to guide clinical practice.
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Drenth JP and Murray CD
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- Endoscopy, Gastrointestinal standards, Evidence-Based Medicine methods, Gastroenterology methods, Gastrointestinal Diseases diagnosis, Humans, Patient Reported Outcome Measures, Quality of Life, Societies, Medical standards, Evidence-Based Medicine standards, Gastroenterology standards, Gastrointestinal Diseases therapy, Practice Guidelines as Topic
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- 2020
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19. Gastroenterological features of COVID-19 and the role of the United European Gastroenterology Journal .
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Magro F and Drenth JP
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- Betacoronavirus, COVID-19, Delivery of Health Care organization & administration, Gastroenterology organization & administration, Humans, Pandemics, Role, SARS-CoV-2, United States, Coronavirus Infections complications, Gastrointestinal Diseases virology, Pneumonia, Viral complications, Serial Publications
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- 2020
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20. Hepatitis C elimination in the Netherlands (CELINE): study protocol for nationwide retrieval of lost to follow-up patients with chronic hepatitis C.
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Isfordink CJ, Brakenhoff SM, van Dijk M, van der Valk M, de Knegt RJ, Arends JE, and Drenth JP
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- Antiviral Agents therapeutic use, Hepacivirus, Humans, Lost to Follow-Up, Netherlands epidemiology, Hepatitis C drug therapy, Hepatitis C, Chronic diagnosis
- Abstract
Background: The Netherlands has a low hepatitis C virus (HCV) prevalence, estimated at 0.16%. Previous studies have shown that up to 30% of the diagnosed HCV population in the Netherlands has been lost to follow-up (LTFU). Retrieval of these patients could halt progression of liver disease in infected patients, reduce the number of infected individuals and limit HCV transmission. Several regional Dutch retrieval projects have already been executed, which demonstrated that retrieval is feasible. Therefore, we initiated a nationwide retrieval project, aiming to achieve microelimination in previously diagnosed but LTFU patients with chronic HCV through retrieval., Methods: Laboratory records will be used to identify possible patients with chronic hepatitis C, defined as either a positive most recent HCV RNA or positive HCV antibodies without known RNA result. Reviewing patient records and obtaining current contact information from municipality databases will identify LTFU patients who are eligible for retrieval. These patients will be invited for outpatient clinic care. The primary outcome of the study is the total number of LTFU patients who have been successfully linked to care., Discussion: Hepatitis C ELimination In the NEtherlands (CELINE) is within the remit of WHO elimination targets and the Dutch National Hepatitis Plan. The methodology of CELINE is based on previously conducted regional retrieval projects and is designed to overcome some of their limitations. After ethical approval was obtained in 2018, the first centre initiated retrieval in 2018 and the project is expected to finish in 2021., Trial Registration Number: NCT04208035., Competing Interests: Competing interests: CJI, SMB and MvD have no conflicts of interest. MvdV declares that the Amsterdam Infection & Immunity Institute Amsterdam UMC, on behalf of MvdV, received fees for participation in advisory boards of Abbvie, Gilead, Johnson & Johnson, Merck Sharp & Dohme (MSD), and ViiV and received independent research grants from Abbvie, Johnson & Johnson, Gilead, and MSD. RJdK declares that the Erasmus University Medical Centre, on behalf of RJdK, received honoraria for consulting/speaking from Gilead, Janssen-Cilag, Bristol-Myers Squibb (BMS), Abbvie, MSD, Roche, and Norgine and received research grants from Gilead, Janssen-Cilag, BMS, and Roche. JEA declares that the University Medical Centre Utrecht, on behalf of JEA, received honoraria for participation in advisory boards of Gilead, Janssen-Cilag, BMS, Abbvie, MSD, and ViiV and received research grants from BMS, Abbvie, and ViiV. JPHD declares that the Radboudumc, on behalf of JPHD, received honoraria or research grants from Novartis, Ipsen, Otsuka, Abbvie, and Gilead. JPHD served as consultant for Gilead and Abbvie, and in the last two years has been member of advisory boards of Otsuka, Norgine Gilead, BMS, Janssen, and Abbvie. JS participated in advisory boards of Gilead and received research grants from Gilead and Abbvie. SW has received honoraria for consulting/speaking from Gilead, Janssen-Cilag, BMS, and Roche, participated in advisory boards of Gilead, BMS, and Abbvie and received research grants from Gilead, Janssen-Cilag BMS, Abbvie, MSD, and Roche. BvH participated in advisory boards of Janssen-Cilag, BMS, Abbvie, MSD, and Norgine and received a research grant from Zambon Pharma. DP has no conflicts of interest to declare. DB has received honoraria for consulting/speaking from MSD, participated in advisory boards of MSD and received research grants from Gilead, Janssen-Cilag, BMS, MSD, and Roche. HB has participated in advisory boards of Gilead. KvE participated in advisory boards of Gilead, Janssen-Cilag, BMS, Abbvie, and MSD and received research grants from Gilead and Janssen-Cilag., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
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21. Common variants in glyoxalase I do not increase chronic pancreatitis risk.
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Kaune T, Hollenbach M, Keil B, Chen JM, Masson E, Becker C, Damm M, Ruffert C, Grützmann R, Hoffmeister A, Te Morsche RHM, Cavestro GM, Zuppardo RA, Saftoiu A, Malecka-Panas E, Głuszek S, Bugert P, Lerch MM, Weiss FU, Zou WB, Liao Z, Hegyi P, Drenth JP, Riedel J, Férec C, Scholz M, Kirsten H, Tóth A, Ewers M, Witt H, Griesmann H, Michl P, and Rosendahl J
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- Female, Genetic Association Studies, Genotype, Glycation End Products, Advanced genetics, Humans, Male, Middle Aged, Oxidative Stress genetics, Pancreatitis, Alcoholic metabolism, Pancreatitis, Alcoholic pathology, Pancreatitis, Chronic metabolism, Pancreatitis, Chronic pathology, Polymorphism, Single Nucleotide genetics, Pyruvaldehyde metabolism, Reactive Oxygen Species metabolism, Risk Factors, Genetic Predisposition to Disease, Lactoylglutathione Lyase genetics, Pancreatitis, Alcoholic genetics, Pancreatitis, Chronic genetics
- Abstract
Introduction: Chronic pancreatitis (CP) may be caused by oxidative stress. An important source of reactive oxygen species (ROS) is the methylglyoxal-derived formation of advanced glycation endproducts (AGE). Methylglyoxal is detoxified by Glyoxalase I (GLO1). A reduction in GLO1 activity results in increased ROS. Single nucleotide polymorphisms (SNPs) of GLO1 have been linked to various inflammatory diseases. Here, we analyzed whether common GLO1 variants are associated with alcoholic (ACP) and non-alcoholic CP (NACP)., Methods: Using melting curve analysis, we genotyped a screening cohort of 223 ACP, 218 NACP patients, and 328 controls for 11 tagging SNPs defined by the SNPinfo LD TAG SNP Selection tool and the functionally relevant variant rs4746. For selected variants the cohorts were extended to up to 1,441 patient samples., Results: In the ACP cohort, comparison of genotypes for rs1937780 between patients and controls displayed an ambiguous result in the screening cohort (p = 0.08). However, in the extended cohort of 1,441 patients no statistically significant association was found for the comparison of genotypes (p = 0.11), nor in logistic regression analysis (p = 0.214, OR 1.072, 95% CI 0.961-1.196). In the NACP screening cohort SNPs rs937662, rs1699012, and rs4746 displayed an ambiguous result when patients were compared to controls in the recessive or dominant model (p = 0.08, 0.08, and 0.07, respectively). Again, these associations were not confirmed in the extended cohorts (rs937662, dominant model: p = 0.07, logistic regression: p = 0.07, OR 1.207, 95% CI 0.985-1.480) or in the replication cohorts for rs4746 (Germany, p = 0.42, OR 1.080, 95% CI 0.673-1.124; France, p = 0.19, OR 0.90, 95% CI 0.76-1.06; China, p = 0.24, OR 1.18, 95% CI 0.90-1.54) and rs1699012 (Germany, Munich; p = 0.279, OR 0.903, 95% CI 0.750-1.087)., Conclusions: Common GLO1 variants do not increase chronic pancreatitis risk., Competing Interests: The authors have declared that no competing interests exist.
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- 2019
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22. United European Gastroenterology Journal and UEG Week.
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Drenth JP
- Subjects
- Digestive System Diseases diagnostic imaging, Endoscopy instrumentation, Gastroenterology statistics & numerical data, Humans, Journal Impact Factor, Periodicals as Topic trends, Social Media standards, Societies, Medical, Digestive System Diseases surgery, Endoscopy methods, European Union organization & administration, Gastroenterology organization & administration, Periodicals as Topic statistics & numerical data
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- 2019
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23. Effect of NGM282, an FGF19 analogue, in primary sclerosing cholangitis: A multicenter, randomized, double-blind, placebo-controlled phase II trial.
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Hirschfield GM, Chazouillères O, Drenth JP, Thorburn D, Harrison SA, Landis CS, Mayo MJ, Muir AJ, Trotter JF, Leeming DJ, Karsdal MA, Jaros MJ, Ling L, Kim KH, Rossi SJ, Somaratne RM, DePaoli AM, and Beuers U
- Subjects
- Biomarkers blood, Biopsy methods, Cholangiography methods, Cholesterol 7-alpha-Hydroxylase metabolism, Double-Blind Method, Drug Monitoring methods, Fibroblast Growth Factors pharmacology, Fibroblast Growth Factors therapeutic use, Humans, Liver Function Tests methods, Male, Middle Aged, Treatment Outcome, Alkaline Phosphatase blood, Bile Acids and Salts biosynthesis, Bile Acids and Salts metabolism, Cholangitis, Sclerosing blood, Cholangitis, Sclerosing diagnosis, Cholangitis, Sclerosing drug therapy, Cholestenones blood, Fibroblast Growth Factors analysis, Liver Cirrhosis blood, Liver Cirrhosis etiology, Liver Cirrhosis prevention & control
- Abstract
Background & Aims: Primary sclerosing cholangitis (PSC) is an inflammatory, cholestatic and progressively fibrotic liver disease devoid of effective medical intervention. NGM282, an engineered, non-tumorigenic FGF19 analogue, potently regulates CYP7A1-mediated bile acid homeostasis. We assessed the activity and safety of NGM282 in patients with PSC., Methods: In this double-blind, placebo-controlled phase II trial, 62 patients who had PSC confirmed by cholangiography or biopsy and an elevated alkaline phosphatase (ALP) >1.5 × the upper limit of normal were randomly assigned 1:1:1 to receive NGM282 1 mg, 3 mg or placebo once daily for 12 weeks. The primary outcome was the change in ALP from baseline to week 12. Secondary and exploratory outcomes included changes in serum biomarkers of bile acid metabolism and fibrosis. Efficacy analysis was by intention-to-treat., Results: At 12 weeks, there were no significant differences in the mean change from baseline in ALP between the NGM282 and placebo groups, and therefore, the primary endpoint was not met. However, NGM282 significantly reduced levels of 7alpha-hydroxy-4-cholesten-3-one (a marker of hepatic CYP7A1 activity, LS mean differences -6.2 ng/ml (95% CI -10.7 to -1.7; p = 0.008) and -9.4 ng/ml (-14.0 to -4.9; p <0.001) in the NGM282 1 mg and 3 mg groups, respectively, compared with placebo) and bile acids. Importantly, fibrosis biomarkers that predict transplant-free survival, including Enhanced Liver Fibrosis score and Pro-C3, were significantly improved following NGM282 treatment. Most adverse events were mild to moderate in severity, with gastrointestinal symptoms more frequent in the NGM282 treatment groups., Conclusions: In patients with PSC, NGM282 potently inhibited bile acid synthesis and decreased fibrosis markers, without significantly affecting ALP levels., Lay Summary: We present for the first time, the clinical and laboratory effects of a first-in-class, engineered analogue of the endocrine hormone FGF19 in patients with primary sclerosing cholangitis (PSC). By incorporating non-invasive markers of fibrosis, beyond standard liver injury markers, we show that NGM282 impacted on fibrosis turnover and hepatic inflammation without changing alkaline phosphatase. Our findings demonstrate the complexities of using highly potent rational agents in PSC, and furthermore challenge the dogma about what the appropriate endpoints should be for trials in PSC., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
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- 2019
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24. United European Gastroenterology Journal making the next step.
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Drenth JP
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- 2019
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25. Prevention of overuse: A view on upper gastrointestinal endoscopy.
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de Jong JJ, Lantinga MA, and Drenth JP
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- Dyspepsia epidemiology, Dyspepsia microbiology, Endoscopy, Gastrointestinal standards, Endoscopy, Gastrointestinal trends, Guideline Adherence standards, Guideline Adherence statistics & numerical data, Guideline Adherence trends, Helicobacter Infections epidemiology, Helicobacter Infections microbiology, Humans, Intersectoral Collaboration, Medical Overuse trends, Practice Guidelines as Topic, Prevalence, Referral and Consultation standards, Referral and Consultation statistics & numerical data, Referral and Consultation trends, Dyspepsia diagnosis, Endoscopy, Gastrointestinal statistics & numerical data, Helicobacter Infections diagnosis, Helicobacter pylori isolation & purification, Medical Overuse statistics & numerical data
- Abstract
Many upper gastrointestinal (GI) endoscopies worldwide are performed for inappropriate indications. This overuse of healthcare negatively affects healthcare quality and puts pressure on endoscopy services. Dyspepsia is one of the most common inappropriate indications for upper GI endoscopy as diagnostic yield is low. Reasons for untimely referral are: unfamiliarity with dyspepsia guidelines, uncertainty about etiology of symptoms, and therapy failure. Unfiltered open-access referrals feed upper GI endoscopy overuse. This review highlights strategies applied to diminish use of upper GI endoscopies for dyspepsia. First, we describe the impact of active guideline implementation. We found improved guideline adherence, but resistance was encountered in the process. Secondly, we show several forms of clinical assessment. While algorithm use reduced upper GI endoscopy volume, effects of referral assessment of individual patients were minor. A third strategy proposed Helicobacter pylori test and treat for all dyspeptic patients. Many upper GI endoscopies can be avoided using this strategy, but outcomes may be prevalence dependent. Lastly, empirical treatment with Proton pump inhibitors achieved symptom relief for dyspepsia and avoided upper GI endoscopies in about two thirds of patients. Changing referral behavior is complex as contributing factors are manifold. A collaboration of multiple strategies is most likely to succeed., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest.
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- 2019
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26. Transabdominal ultrasound and endoscopic ultrasound for diagnosis of gallbladder polyps.
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Wennmacker SZ, Lamberts MP, Di Martino M, Drenth JP, Gurusamy KS, and van Laarhoven CJ
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- Adenoma diagnostic imaging, Adult, Carcinoma diagnostic imaging, Diagnosis, Differential, Endosonography, Gallbladder Diseases pathology, Gallbladder Neoplasms diagnostic imaging, Humans, Polyps pathology, Sensitivity and Specificity, Gallbladder Diseases diagnostic imaging, Polyps diagnostic imaging, Ultrasonography methods
- Abstract
Background: Approximately 0.6% to 4% of cholecystectomies are performed because of gallbladder polyps. The decision to perform cholecystectomy is based on presence of gallbladder polyp(s) on transabdominal ultrasound (TAUS) or endoscopic ultrasound (EUS), or both. These polyps are currently considered for surgery if they grow more than 1 cm. However, non-neoplastic polyps (pseudo polyps) do not need surgery, even when they are larger than 1 cm. True polyps are neoplastic, either benign (adenomas) or (pre)malignant (dysplastic polyps/carcinomas). True polyps need surgery, especially if they are premalignant or malignant. There has been no systematic review and meta-analysis on the accuracy of TAUS and EUS in the diagnosis of gallbladder polyps, true gallbladder polyps, and (pre)malignant polyps., Objectives: To summarise and compare the accuracy of transabdominal ultrasound (TAUS) and endoscopic ultrasound (EUS) for the detection of gallbladder polyps, for differentiating between true and pseudo gallbladder polyps, and for differentiating between dysplastic polyps/carcinomas and adenomas/pseudo polyps of the gallbladder in adults., Search Methods: We searched the Cochrane Library, MEDLINE, Embase, Science Citation Index Expanded, and trial registrations (last date of search 09 July 2018). We had no restrictions regarding language, publication status, or prospective or retrospective nature of the studies., Selection Criteria: Studies reporting on the diagnostic accuracy data (true positive, false positive, false negative and true negative) of the index test (TAUS or EUS or both) for detection of gallbladder polyps, differentiation between true and pseudo polyps, or differentiation between dysplastic polyps/carcinomas and adenomas/pseudo polyps. We only accepted histopathology after cholecystectomy as the reference standard, except for studies on diagnosis of gallbladder polyp. For the latter studies, we also accepted repeated imaging up to six months by TAUS or EUS as the reference standard., Data Collection and Analysis: Two authors independently screened abstracts, selected studies for inclusion, and collected data from each study. The quality of the studies was evaluated using the QUADAS-2 tool. The bivariate random-effects model was used to obtain summary estimates of sensitivity and specificity, to compare diagnostic performance of the index tests, and to assess heterogeneity., Main Results: A total of 16 studies were included. All studies reported on TAUS and EUS as separate tests and not as a combination of tests. All studies were at high or unclear risk of bias, ten studies had high applicability concerns in participant selection (because of inappropriate participant exclusions) or reference standards (because of lack of follow-up for non-operated polyps), and three studies had unclear applicability concerns in participant selection (because of high prevalence of gallbladder polyps) or index tests (because of lack of details on ultrasound equipment and performance). A meta-analysis directly comparing results of TAUS and EUS in the same population could not be performed because only limited studies executed both tests in the same participants. Therefore, the results below were obtained only from indirect test comparisons. There was significant heterogeneity amongst all comparisons (target conditions) on TAUS and amongst studies on EUS for differentiating true and pseudo polyps.Detection of gallbladder polyps: Six studies (16,260 participants) used TAUS. We found no studies on EUS. The summary sensitivity and specificity of TAUS for the detection of gallbladder polyps was 0.84 (95% CI 0.59 to 0.95) and 0.96 (95% CI 0.92 to 0.98), respectively. In a cohort of 1000 people, with a 6.4% prevalence of gallbladder polyps, this would result in 37 overdiagnosed and seven missed gallbladder polyps.Differentiation between true polyp and pseudo gallbladder polyp: Six studies (1078 participants) used TAUS; the summary sensitivity was 0.68 (95% CI 0.44 to 0.85) and the summary specificity was 0.79 (95% CI 0.57 to 0.91). Three studies (209 participants) used EUS; the summary sensitivity was 0.85 (95% CI 0.46 to 0.97) and the summary specificity was 0.90 (95% CI 0.78 to 0.96). In a cohort of 1000 participants with gallbladder polyps, with 10% having true polyps, this would result in 189 overdiagnosed and 32 missed true polyps by TAUS, and 90 overdiagnosed and 15 missed true polyps by EUS. There was no evidence of a difference between the diagnostic accuracy of TAUS and EUS (relative sensitivity 1.06, P = 0.70, relative specificity 1.15, P = 0.12).Differentiation between dysplastic polyps/carcinomas and adenomas/pseudo polyps of the gallbladder: Four studies (1,009 participants) used TAUS; the summary sensitivity was 0.79 (95% CI 0.62 to 0.90) and the summary specificity was 0.89 (95% CI 0.68 to 0.97). Three studies (351 participants) used EUS; the summary sensitivity was 0.86 (95% CI 0.76 to 0.92) and the summary specificity was 0.92 (95% CI 0.85 to 0.95). In a cohort of 1000 participants with gallbladder polyps, with 5% having a dysplastic polyp/carcinoma, this would result in 105 overdiagnosed and 11 missed dysplastic polyps/carcinomas by TAUS and 76 overdiagnosed and seven missed dysplastic polyps/carcinomas by EUS. There was no evidence of a difference between the diagnostic accuracy of TAUS and EUS (log likelihood test P = 0.74)., Authors' Conclusions: Although TAUS seems quite good at discriminating between gallbladder polyps and no polyps, it is less accurate in detecting whether the polyp is a true or pseudo polyp and dysplastic polyp/carcinoma or adenoma/pseudo polyp. In practice, this would lead to both unnecessary surgeries for pseudo polyps and missed cases of true polyps, dysplastic polyps, and carcinomas. There was insufficient evidence that EUS is better compared to TAUS in differentiating between true and pseudo polyps and between dysplastic polyps/carcinomas and adenomas/pseudo polyps. The conclusions are based on heterogeneous studies with unclear criteria for diagnosis of the target conditions and studies at high or unclear risk of bias. Therefore, results should be interpreted with caution. Further studies of high methodological quality, with clearly stated criteria for diagnosis of gallbladder polyps, true polyps, and dysplastic polyps/carcinomas are needed to accurately determine diagnostic accuracy of EUS and TAUS.
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- 2018
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27. Ethanol sclerotherapy or polidocanol sclerotherapy for symptomatic hepatic cysts.
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Wijnands TF, Schoenemeier B, Potthoff A, Gevers TJ, Groenewoud H, Gebel MJ, Rifai K, Manns MP, and Drenth JP
- Abstract
Background: Over the past decades, multiple approaches to aspiration sclerotherapy of large symptomatic hepatic cysts have been investigated. However, comparative data are scarce., Objective: The objective of this article is to compare cyst reduction, symptomatic relief, and adverse events between ethanol sclerotherapy and polidocanol sclerotherapy., Methods: This retrospective study included adults having a symptomatic hepatic cyst treated at a European tertiary referral center with ethanol sclerotherapy (Center 1) or polidocanol-sclerotherapy (Center 2). We compared cyst diameter reduction (%) and symptom improvement (yes/no) within 12 months' post-treatment between centers using multivariate regression analyses adjusted for confounding factors. Finally, we compared adverse events using Fisher's exact test., Results: We included 71 patients from Center 1 and 66 patients from Center 2 (median age 57 years; 126/137 (92%) female). Cyst reduction was comparable between Centers 1 and 2: 37.5% (IQR 15.7-61.0%) versus 44.2% (IQR 24.6-60.5%), respectively ( p = 0.35). Correspondingly, symptomatic relief was comparable: 30/53 (56.6%) versus 43/66 (65.2%), respectively ( p = 0.88). Center 1 reported significantly more (11 versus 3; p = 0.047) adverse events than Center 2., Conclusion: We found comparable cyst reduction and symptomatic relief rates between ethanol- and polidocanol sclerotherapy, while adverse events occurred more often in the ethanol group. Prospective studies focused on clinical response are needed to further explore differences between approaches.
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- 2018
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28. Impact of liver volume on polycystic liver disease-related symptoms and quality of life.
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Neijenhuis MK, Kievit W, Verheesen SM, D'Agnolo HM, Gevers TJ, and Drenth JP
- Abstract
Background: Symptoms in polycystic liver disease (PLD) are thought to be caused by compression of organs and structures by the enlarged liver., Aim: The aim of this article is to assess the impact of liver volume on symptoms and quality of life (QoL) in PLD., Methods: We included PLD patients from two prospective studies that used the PLD-questionnaire (PLD-Q) for symptom assessment. QoL was assessed through SF-36, summarized in a physical (PCS) and mental (MCS) component score. Liver volume was correlated with PLD-Q total scores. Patients were classified based on height-corrected liver volume in mild (<1600 ml), moderate (1600-3200 ml), and severe (>3200 ml) disease. PLD-Q and QoL (PCS and MCS) scores were compared across disease stages., Results: We included 82 of 131 patients from the original studies (disease stages; mild n = 26, moderate n = 33, and severe n = 23). Patients with larger liver volume reported higher symptom burden ( r = 0.516, p < 0.001). Symptom scores increased with disease progression, except for abdominal pain ( p = 0.088). PCS decreased with advancing disease ( p < 0.001), in contrast to MCS ( p = 0.055). Moderate ( p = 0.007) and severe ( p < 0.001) PLD patients had lower PCS scores than the general population., Conclusion: PLD with larger liver volume is more likely to be symptomatic and is associated with lower QoL.
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- 2018
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29. The majority of hepatitis C patients treated with direct acting antivirals are at risk for relevant drug-drug interactions.
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Smolders EJ, Berden FA, de Kanter CT, Kievit W, Drenth JP, and Burger DM
- Abstract
Background: Direct-acting antivirals have improved treatment of chronic hepatitis C virus infection significantly. Direct-acting antivirals inhibit/induce and can also be substrates of drug-metabolising enzymes and transporters. This increases the risk for drug-drug interactions., Objective: The purpose of this study was to predict drug-drug interactions with co-medication used by hepatitis C virus-infected patients., Methods: We assembled a nationwide cohort of hepatitis C patients and collected cross-sectional data on co-medication use. We compiled a list of currently available direct-acting antiviral regimens and cross-checked for potential drug-drug interactions with used co-medication., Results: The cohort included 461 patients of which 77% used co-medication. We identified 260 drugs used as co-medication. Antidepressants (7.4%), proton pump inhibitors (7.1%) and benzodiazepines (7.1%) were most frequently used. Of the patients, 60% were at risk for a clinically relevant drug-drug interaction with at least one of the direct-acting antiviral regimens. Interactions were most common with paritaprevir/ritonavir/ombitasvir/dasabuvir and least interactions were predicted with grazoprevir/elbasvir., Conclusion: Co-medication use is rich in frequency and diversity in chronic hepatitis C patients. The majority of patients are at risk for drug-drug interactions which may affect efficacy or toxicity of direct-acting antivirals or co-medication. The most recently introduced direct-acting antivirals are associated with a lower risk of drug-drug interactions.
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- 2017
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30. Novel treatment protocol for ameliorating refractory, chronic pain in patients with autosomal dominant polycystic kidney disease.
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Casteleijn NF, van Gastel MD, Blankestijn PJ, Drenth JP, de Jager RL, Leliveld AM, Stellema R, Wolff AP, Groen GJ, and Gansevoort RT
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- Adult, Anesthetics, Local adverse effects, Autonomic Denervation adverse effects, Chronic Pain diagnosis, Chronic Pain etiology, Chronic Pain physiopathology, Clinical Protocols, Female, Humans, Male, Middle Aged, Nerve Block adverse effects, Pain Measurement, Polycystic Kidney, Autosomal Dominant diagnosis, Recurrence, Time Factors, Treatment Outcome, Anesthetics, Local administration & dosage, Autonomic Denervation methods, Catheter Ablation adverse effects, Celiac Plexus drug effects, Chronic Pain therapy, Kidney innervation, Nerve Block methods, Polycystic Kidney, Autosomal Dominant complications, Splanchnic Nerves surgery
- Abstract
Autosomal dominant polycystic kidney disease (ADPKD) patients can suffer from chronic pain that can be refractory to conventional treatment, resulting in a wish for nephrectomy. This study aimed to evaluate the effect of a multidisciplinary treatment protocol with sequential nerve blocks on pain relief in ADPKD patients with refractory chronic pain. As a first step a diagnostic, temporary celiac plexus block with local anesthetics was performed. If substantial pain relief was obtained, the assumption was that pain was relayed via the celiac plexus and major splanchnic nerves. When pain recurred, patients were then scheduled for a major splanchnic nerve block with radiofrequency ablation. In cases with no pain relief, it was assumed that pain was relayed via the aortico-renal plexus, and catheter-based renal denervation was performed. Sixty patients were referred, of which 44 were eligible. In 36 patients the diagnostic celiac plexus block resulted in substantial pain relief with a change in the median visual analogue scale (VAS) score pre-post intervention of 50/100. Of these patients, 23 received a major splanchnic nerve block because pain recurred, with a change in median VAS pre-post block of 53/100. In 8 patients without pain relief after the diagnostic block, renal denervation was performed in 5, with a borderline significant change in the median VAS pre-post intervention of 20/100. After a median follow-up of 12 months, 81.8% of the patients experienced a sustained improvement in pain intensity, indicating that our treatment protocol is effective in obtaining pain relief in ADPKD patients with refractory chronic pain., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
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- 2017
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31. The gap between registration trials and real world in hepatitis C is closing.
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Berden FA, Vuik FE, Drenth JP, and Kievit W
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- Antiviral Agents adverse effects, Humans, Linear Models, Antiviral Agents therapeutic use, Biomedical Research, Clinical Trials as Topic statistics & numerical data, Hepacivirus drug effects, Hepatitis C, Chronic drug therapy, Patient Selection
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- 2017
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32. Identification of the Best Direct-Acting Antiviral Regimen for Patients With Hepatitis C Virus Genotype 3 Infection: A Systematic Review and Network Meta-analysis.
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Berden FA, Aaldering BR, Groenewoud H, IntHout J, Kievit W, and Drenth JP
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- Drug Therapy, Combination methods, Hepacivirus isolation & purification, Humans, Network Meta-Analysis, Treatment Outcome, Antiviral Agents therapeutic use, Genotype, Hepacivirus classification, Hepacivirus genetics, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic virology
- Abstract
Background & Aims: Direct-acting antivirals (DAAs) are effective in the treatment of chronic hepatitis C virus (HCV) infection, although results for patients infected with genotype 3 are suboptimal. There are several regimens available, however, direct comparisons have not been made and are unlikely to occur. We aimed to identify the most effective DAA regimen for patients infected with HCV genotype 3 and to assess the role of ribavirin., Methods: We conducted a systematic search of PubMed, Embase, and Web of Science databases through March 2016. We performed a Bayesian network meta-analysis using a random-effects model to indirectly compare regimens in patients with and without cirrhosis. We calculated mean estimated sustained virologic response (SVR) with 95% credible intervals (95% CrI) per regimen and effect of ribavirin as odds ratio. We focused on current recommended regimens and regimens under evaluation by regulatory authorities., Results: Our search identified 2167 articles; 27 studies (comprising 3415 patients) were included. Among patients without cirrhosis, the greatest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir with ribavirin (99%; 95% CrI, 98%-100%) and without ribavirin (97%; 95% CrI, 95%-99%), sofosbuvir + daclatasvir + ribavirin (96%; 95% CrI, 92%-98%), and sofosbuvir + peginterferon + ribavirin (95%; 95% CrI, 91%-98%), all for 12 weeks. Among patients with cirrhosis, the highest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir for 24 weeks (96%; 95% CrI, 92%-99%), sofosbuvir + daclatasvir + ribavirin for 24 weeks (94%; 95% CrI, 87%-98%), and sofosbuvir + velpatasvir + ribavirin for 12 weeks (94%; 95% CrI, 86%-98%). Ribavirin increases efficacy in patients with and without cirrhosis (odds ratio, 2.6-4.5)., Conclusions: An indirect comparison of DAA-based treatments, using Bayesian network meta-analysis, found regimens containing sofosbuvir and velpatasvir to be the best option for patients with HCV genotype 3 infection. Our analyses indicated that ribavirin significantly increases SVR rates and should be considered if tolerated., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)
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- 2017
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33. Familial gain-of-function Na v 1.9 mutation in a painful channelopathy.
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Han C, Yang Y, Te Morsche RH, Drenth JP, Politei JM, Waxman SG, and Dib-Hajj SD
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- Ganglia, Spinal physiopathology, Humans, Membrane Potentials physiology, Mutation, Missense genetics, NAV1.9 Voltage-Gated Sodium Channel genetics, Neurons physiology, Patch-Clamp Techniques methods, Channelopathies diagnosis, Channelopathies genetics, Mutation genetics, NAV1.7 Voltage-Gated Sodium Channel genetics, Pain genetics
- Abstract
Objective: Gain-of-function mutations in Na
v 1.9 have been identified in three families with rare heritable pain disorders, and in patients with painful small-fibre neuropathy. Identification and functional assessment of new Nav 1.9 mutations will help to elucidate the phenotypic spectrum of Nav 1.9 channelopathies., Methods: Patients from a large family with early-onset pain symptoms were evaluated by clinical examination and genomic screening for mutations in SCN9A and SCN11A . Electrophysiological recordings and multistate modelling analysis were implemented for functional analyses., Results: A novel Nav 1.9 mutation, p.Arg222His, was identified in patients with early-onset pain in distal extremities including joints and gastrointestinal disturbances, but was absent from an asymptomatic blood relative. This mutation alters channel structure by substituting the highly conserved first arginine residue in transmembrane segment 4 (domain 1), the voltage sensor, with histidine. Voltage-clamp recordings demonstrate a hyperpolarising shift and acceleration of activation of the p.Arg222His mutant channel, which make it easier to open the channel. When expressed in dorsal root ganglion neurons, mutant p.Arg222His channels increase excitability via a depolarisation of resting potential and increased evoked firing., Conclusions: This study expands the spectrum of heritable pain disorders linked to gain-of-function mutations in Nav 1.9, strengthening human validation of this channel as a potential therapeutic target for pain., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)- Published
- 2017
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34. Building pancreatic organoids to aid drug development.
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Wills ES and Drenth JP
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- Humans, Pancreatic Neoplasms, Organoids, Pancreas
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- 2017
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35. Specific Radiological Imaging Findings in Patients With Hereditary Pancreatitis During a Long Follow-up of Disease.
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van Esch AA, Drenth JP, and Hermans JJ
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- Adolescent, Adult, Atrophy diagnostic imaging, Child, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Pancreas pathology, Pancreatic Ducts pathology, Retrospective Studies, Tomography, X-Ray Computed methods, Ultrasonography methods, Young Adult, Pancreas diagnostic imaging, Pancreatic Ducts diagnostic imaging, Pancreatitis, Chronic diagnostic imaging
- Abstract
Objectives: Hereditary pancreatitis (HP) is characterized by recurrent episodes of inflammation of the pancreas. Radiological imaging is used to diagnose HP and to monitor complications. The aim of this study was to describe specific imaging findings in HP., Methods: We retrospectively collected data of HP patients with serial imaging and reviewed all radiological imaging studies (transabdominal ultrasonography, computed tomography, and magnetic resonance imaging)., Results: We included 15 HP patients, with a mean age of 32.5 years (range, 9-61 years) and mean disease duration of 24.1 years (range, 6-42 years). In total, 152 imaging studies were reviewed. Seventy-three percent of patients had a dilated main pancreatic duct (MPD) (width 3.5-18 mm). The MPD varied in size during disease course, with temporary reduction in diameter after drainage procedures. A severe dilated MPD (>10 mm) often coincided with presence of intraductal calcifications (size, 1-12 mm). In 73% of patients, pancreatic parenchyma atrophy occurred, which did not correlate with presence of exocrine or endocrine insufficiency., Conclusions: In HP, the MPD diameter increases with time, mostly without dilated side branches, and is often accompanied by large intraductal calcifications. The size of the MPD is independent of disease state. Atrophy of pancreatic parenchyma is not correlated with exocrine or endocrine insufficiency.
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- 2017
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36. Decreased tacrolimus plasma concentrations during HCV therapy: a drug-drug interaction or is there an alternative explanation?
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Smolders EJ, Pape S, de Kanter CT, van den Berg AP, Drenth JP, and Burger DM
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- Aged, Antiviral Agents pharmacokinetics, Cytochrome P-450 Enzyme System metabolism, Hepatitis C, Chronic surgery, Humans, Immunosuppressive Agents pharmacokinetics, Liver Transplantation, Male, Middle Aged, Tacrolimus pharmacokinetics, Transplant Recipients, Antiviral Agents administration & dosage, Drug Interactions, Hepatitis C, Chronic drug therapy, Immunosuppressive Agents blood, Plasma chemistry, Tacrolimus blood
- Abstract
Chronic hepatitis C virus (HCV) infection can cause severe liver cirrhosis, for which liver transplantation is the only therapy. To prevent organ rejection, transplanted patients are treated with immunosuppressive agents. We describe two transplanted patients treated with tacrolimus who were simultaneously treated with direct-acting antivirals (DAAs) for their chronic HCV infection. No pharmacokinetic drug-drug interactions (DDIs) were expected between tacrolimus and the selected DAAs. However, in both patients, tacrolimus plasma concentrations decreased during HCV treatment. We hypothesise that decreased plasma concentrations were not caused by a DDI but were an indirect result of the clearance of the HCV infection. During chronic HCV infection, pro-inflammatory cytokines may inhibit cytochrome P450 (CYP) enzymes, which are primarily responsible for tacrolimus metabolism. If this is true, then with clearance of the virus the activity of these enzymes will normalise and tacrolimus metabolism will increase. These changes were clinically relevant because the tacrolimus dosage needed to be adjusted. Therefore, physicians should be aware that CYP substrates with narrow therapeutic ranges might require dose adaption during HCV therapy with DAAs., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)
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- 2017
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37. Common single nucleotide polymorphisms in transient receptor potential melastatin type 6 increase the risk for proton pump inhibitor-induced hypomagnesemia: a case-control study.
- Author
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Hess MW, de Baaij JH, Broekman MM, Bisseling TM, Haarhuis BJ, Tan AC, Te Morsche RH, Hoenderop JG, Bindels RJ, and Drenth JP
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- Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Humans, Magnesium Deficiency blood, Male, Middle Aged, Prospective Studies, Proton Pump Inhibitors adverse effects, Young Adult, Magnesium blood, Magnesium Deficiency chemically induced, Polymorphism, Single Nucleotide, Proton Pump Inhibitors administration & dosage, TRPM Cation Channels genetics
- Abstract
Objective: Proton pump inhibitors (PPIs) are effective drugs for the treatment of gastric acid-related disorders. Serious adverse events are rare for PPIs, but recent data suggest that PPIs cause hypomagnesemia. The aim of this study was to estimate the frequency of PPI-induced hypomagnesemia and to define the risk factors for its development., Materials and Methods: A total of 133 chronic users of PPIs were enrolled and patients were distinguished on the basis of their serum Mg concentrations. Common single nucleotide polymorphisms (SNPs) in the candidate gene, transient receptor potential melastatin type 6 (TRPM6), were screened., Results: Seventeen out of 133 patients had PPI-induced hypomagnesemia. The duration of PPI use was longer in those with hypomagnesemia (7.7 vs. 5.2 years). Two common SNPs in TRPM6 (rs3750425 and rs2274924) increased the risk for PPI-induced hypomagnesemia by 5.8-fold., Conclusion: We found hypomagnesemia in 13% of PPI users. SNPs in TRPM6 drive the risk of developing hypomagnesemia during chronic PPI use.
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- 2017
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38. Daclatasvir 30 mg/day is the correct dose for patients taking atazanavir/cobicistat.
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Smolders EJ, Colbers EP, de Kanter CT, Velthoven-Graafland K, Drenth JP, and Burger DM
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- Adult, Anti-HIV Agents adverse effects, Anti-HIV Agents pharmacokinetics, Atazanavir Sulfate pharmacokinetics, Carbamates, Cobicistat pharmacokinetics, Cross-Over Studies, Cytochrome P-450 CYP3A Inhibitors pharmacokinetics, Cytochrome P-450 CYP3A Inhibitors therapeutic use, Female, Humans, Imidazoles pharmacokinetics, Male, Middle Aged, Prospective Studies, Pyrrolidines, Ritonavir pharmacokinetics, Ritonavir therapeutic use, Valine analogs & derivatives, Young Adult, Anti-HIV Agents therapeutic use, Atazanavir Sulfate therapeutic use, Cobicistat therapeutic use, HIV Infections drug therapy, Imidazoles administration & dosage, Imidazoles therapeutic use
- Abstract
Background: Atazanavir is boosted with the cytochrome P450 (CYP) 3A4 inhibitor ritonavir. When combined with the CYP3A4 substrate daclatasvir, the daclatasvir dosage should be reduced from 60 to 30 mg once daily. Recently, cobicistat was licensed as a CYP3A booster and used with atazanavir., Objectives: To determine whether the fixed-dose combination of atazanavir/cobicistat has an influence on daclatasvir pharmacokinetics comparable to that of the separate agents atazanavir and ritonavir., Methods: A prospective, open-label, two-period, randomized, cross-over trial was performed in 16 healthy subjects (NCT02565888). Treatment consisted of 300/100 mg of atazanavir/ritonavir plus 30 mg of daclatasvir once daily (reference) and a second period of 300/150 mg of atazanavir/cobicistat plus 30 mg of daclatasvir once daily (test). A 24 h pharmacokinetic, steady-state curve was recorded for all drugs. Geometric mean ratios (GMRs) with 90% CI were calculated for daclatasvir and atazanavir AUC
τ and Cmax to compare the effect of both treatments (test versus reference). Laboratory safety and adverse events were evaluated throughout the trial., Results: All 16 healthy subjects completed the study. Median (range) age and BMI were 48.5 (21-55) years and 24.5 (19.0-29.2) kg/m2 , respectively. Pharmacokinetic parameters of ritonavir and cobicistat were comparable to those in the literature. The GMRs (90% CI) of daclatasvir AUCτ and Cmax (test versus reference) were 101% (92%-111%) and 97% (89%-106%), respectively. Atazanavir GMRs (90% CI) of AUCτ and Cmax were 82% (75%-79%) and 74% (68%-81%), respectively. No serious adverse events were reported., Conclusions: Atazanavir/cobicistat and atazanavir/ritonavir had a similar influence on daclatasvir pharmacokinetics in healthy volunteers. Daclatasvir at 30 mg once daily is the correct dose when combined with atazanavir/cobicistat., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)- Published
- 2017
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39. Predictors of treatment response following aspiration sclerotherapy of hepatic cysts: an international pooled analysis of individual patient data.
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Wijnands TF, Ronot M, Gevers TJ, Benzimra J, Kool LJ, Vilgrain V, and Drenth JP
- Subjects
- Adult, Aged, Cysts diagnostic imaging, Drainage, Female, Humans, Liver Diseases diagnostic imaging, Logistic Models, Male, Middle Aged, Multivariate Analysis, Suction, Surgery, Computer-Assisted, Tomography, X-Ray Computed, Treatment Outcome, Ultrasonography, Cysts therapy, Ethanol therapeutic use, Liver Diseases therapy, Sclerosing Solutions therapeutic use, Sclerotherapy methods
- Abstract
Objectives: To identify predictive variables of treatment response following aspiration sclerotherapy of large symptomatic hepatic cysts., Methods: We collected individual patient data from two tertiary referral centres and included all patients treated with aspiration sclerotherapy of a large (>5 cm), symptomatic hepatic cyst. At six months, clinical response was defined as complete or incomplete. Secondary, suboptimal technical response was defined as lower quartile of cyst reduction. Predictive variables of clinical and technical response were analyzed by logistic regression analysis., Results: We included 86 patients (58 ± 10 years; female 90 %). Complete clinical response rate was 55 %. Median cyst diameter and volume reduction were 71 % (IQR 50-87 %) and 98 % (IRQ 88-100 %), respectively. Patients with complete clinical response had a significantly higher cyst reduction compared to incomplete responders (OR 1.02, 95 % CI 1.00-1.04). Aspiration of haemorrhagic cyst fluid (OR 4.39, 95 % CI 1.34-14.39) or a lower cyst reduction at one month (OR 1.06, 95 % CI 1.02-1.10) was associated with a suboptimal technical response at six months., Conclusion: Complete clinical response is associated with effective cyst reduction. Aspiration of haemorrhagic cyst fluid or a restricted diameter reduction at one month predicts a suboptimal technical treatment response, however, these variables did not predict symptom disappearance., Key Points: • Aspiration sclerotherapy of hepatic cysts shows excellent clinical and technical efficacy. • Optimal clinical responders have a markedly higher cyst reduction. • Haemorrhagic aspirate and a strong fluid reaccumulation predict suboptimal cyst reduction.
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- 2017
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40. Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study.
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Lantinga MA, D'Agnolo HM, Casteleijn NF, de Fijter JW, Meijer E, Messchendorp AL, Peters DJ, Salih M, Spithoven EM, Soonawala D, Visser FW, Wetzels JF, Zietse R, Drenth JP, and Gansevoort RT
- Subjects
- Adolescent, Adult, Cysts epidemiology, Female, Glomerular Filtration Rate, Humans, Liver Diseases epidemiology, Male, Middle Aged, Peptides, Cyclic adverse effects, Polycystic Kidney, Autosomal Dominant complications, Somatostatin administration & dosage, Somatostatin adverse effects, Young Adult, Cysts etiology, Liver Diseases etiology, Peptides, Cyclic administration & dosage, Polycystic Kidney, Autosomal Dominant drug therapy, Somatostatin analogs & derivatives
- Abstract
Introduction and Aims: The DIPAK-1 Study investigates the reno- and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several episodes of hepatic cyst infection, all during lanreotide treatment. We describe these events and provide a review of the literature., Methods: The DIPAK-1 Study is an ongoing investigator-driven, randomized, controlled, open-label multicenter trial. Patients (ADPKD, ages 18-60 years, estimated glomerular filtration rate 30-60 mL/min/1.73 m
2 ) were randomized 1:1 to receive lanreotide 120 mg subcutaneously every 28 days or standard care during 120 weeks. Hepatic cyst infection was diagnosed by local physicians., Results: We included 309 ADPKD patients of which seven (median age 53 years [interquartile range: 48-55], 71% female, median estimated glomerular filtration rate 42 mL/min/1.73 m2 [interquartile range: 41-58]) developed eight episodes of hepatic cyst infection during 342 patient-years of lanreotide use (0.23 cases per 10 patient-years). These events were limited to patients receiving lanreotide (p < 0.001 vs. standard care). Baseline characteristics were similar between subjects who did or did not develop a hepatic cyst infection during lanreotide use, except for a history of hepatic cyst infection (29 vs. 0.7%, p < 0.001). Previous studies with somatostatin analogs reported cyst infections, but did not identify a causal relationship., Conclusions: These data suggest an increased risk for hepatic cyst infection during use of somatostatin analogs, especially in ADPKD patients with a history of hepatic cyst infection. The main results are still awaited to fully appreciate the risk-benefit ratio. CLINICALTRIALS., Gov Identifier: NCT 01616927., Competing Interests: Compliance with Ethical Standards Funding The DIPAK-1 study is made possible by a grant from the Dutch Kidney Foundation (CP10.12), with Ipsen Farmaceutica B.V., the Netherlands acting as a minor co-sponsor. The Dutch Kidney Foundation and Ipsen had no role in the design or conduct of the study, or in the writing and submission of the manuscript. Conflict of interest Marten A. Lantinga, Hedwig M.A. D’Agnolo, Niek F. Casteleijn, Johan W. de Fijter, Esther Meijer, Annemarie L. Messchendorp, Dorien J.M. Peters, Mahdi Salih, Darius Soonawala, Folkert W. Visser, and Jack F.M. Wetzels have no conflicts of interest that are directly relevant to the content of this study. Edwin M. Spithoven has received payment for an Otsuka presentation about the epidemiology of ADPKD and future perspectives. Robert Zietse has received previous grant support from Ipsen. Joost P.H. Drenth has received previous grant support from Ipsen and Novartis. Ron T. Gansevoort holds the rights on the Orphan Designation status of lanreotide for the indication ADPKD, which was granted by the European Medicines Agency (EU/3/15/1514). Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Consent for publication Informed consent was obtained from all individual participants included in the study.- Published
- 2017
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41. Management of renal cyst infection in patients with autosomal dominant polycystic kidney disease: a systematic review.
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Lantinga MA, Casteleijn NF, Geudens A, de Sévaux RG, van Assen S, Leliveld AM, Gansevoort RT, and Drenth JP
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- Female, Humans, Infections diagnosis, Infections etiology, Male, Middle Aged, Prognosis, Infections therapy, Kidney Transplantation adverse effects, Polycystic Kidney, Autosomal Dominant complications
- Abstract
Background: Renal cyst infection is one of the complications faced by patients with autosomal dominant polycystic kidney disease (ADPKD). Cyst infection is often difficult to treat and potentially leads to sepsis and death. No evidence-based treatment strategy exists. We therefore performed a systematic review to develop an effective approach for the management of renal cyst infection in ADPKD patients based on the literature., Methods: A systematic search was performed in PubMed (January 1948-February 2014), EMBASE (January 1974-February 2014) and the Cochrane Library (until February 2014) according to the PRISMA guidelines., Results: We identified 60 manuscripts that included 85 ADPKD patients with renal cyst infection (aged 52 ± 12 years, 45% male, 27% on dialysis, 13% history of renal transplantation and 6% diabetes mellitus). Included patients received a total of 160 treatments of which 92 were antimicrobial, 29 percutaneous and 39 surgical. Initial management often consisted of antimicrobials (79%), and quinolone-based regimens were favoured (34%). Overall, 61% of patients failed initial treatment, but treatment failure has decreased over time (before the year 2000: 75%; during and after the year 2000: 51%, P = 0.03). Post-renal obstruction, urolithiasis, atypical or resistant pathogens, short duration of antimicrobial treatment and renal function impairment were documented in patients failing treatment., Conclusions: First-line treatment of renal cyst infection in ADPKD consists of antimicrobials and is associated with a high rate of failure, but treatment success has increased over recent years. A large-scale unbiased registry is needed to define the optimal strategy for renal cyst infection management in ADPKD., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
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- 2017
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42. Center is an important indicator for choice of invasive therapy in polycystic liver disease.
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D'Agnolo HM, Kievit W, van Munster KN, van der Laan JJ, Nevens F, and Drenth JP
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- Adult, Age Factors, Cross-Sectional Studies, Female, Follow-Up Studies, Genes, Dominant, Humans, Liver Transplantation, Male, Middle Aged, Multivariate Analysis, Phenotype, Polycystic Kidney, Autosomal Dominant surgery, Registries, Retrospective Studies, Treatment Outcome, Cysts surgery, Hospitals classification, Liver Diseases surgery, Sclerotherapy methods
- Abstract
Polycystic liver disease (PLD) is a rare genetic disorder with progressive cyst growth as the primary phenotype. Therapy consists of volume reduction through invasive surgical or radiological procedures. To understand the process of treatment decision, our aim was to identify factors that increased the likelihood of treatment. We performed a cross-sectional study using an international population of patients with PLD. We collected data on the following therapies: liver transplantation, resection, fenestration, and aspiration sclerotherapy. Data on the potential determinants, sex, center, autosomal dominant polycystic kidney disease (ADPKD), autosomal dominant polycystic liver disease (ADPLD), age at diagnosis, symptoms, and phenotype, were included. We corrected for follow-up time. We included 578 patients in our study, and 35% underwent invasive therapy. Multivariate regression analysis showed that number of symptoms and age at diagnosis of PLD increased the likelihood of treatment (respectively, RR: 1.4, P < 0.001 and RR = 1.4, P = 0.03). The choice for liver transplantation or aspiration sclerotherapy was center dependent (RR: 0.7, P < 0.001 and RR: 1.1, P = 0.03, respectively). The results of our international cross-sectional study suggest that a higher number of symptoms and every 10 years of PLD diagnosis increase the risk to undergo treatment by 40%. The choice to elect a particular modality is center dependent., (© 2016 Steunstichting ESOT.)
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- 2017
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43. Efficacy and Safety of Aspiration Sclerotherapy of Simple Hepatic Cysts: A Systematic Review.
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Wijnands TF, Görtjes AP, Gevers TJ, Jenniskens SF, Kool LJ, Potthoff A, Ronot M, and Drenth JP
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- Alcoholic Intoxication epidemiology, Alcoholic Intoxication prevention & control, Causality, Comorbidity, Cysts diagnosis, Ethanol adverse effects, Ethanol therapeutic use, Female, Humans, Liver Diseases diagnosis, Male, Pain prevention & control, Patient Safety, Prevalence, Risk Factors, Sclerosing Solutions adverse effects, Sclerosing Solutions therapeutic use, Sclerotherapy adverse effects, Suction statistics & numerical data, Treatment Outcome, Cysts epidemiology, Cysts therapy, Liver Diseases epidemiology, Liver Diseases therapy, Pain epidemiology, Sclerotherapy statistics & numerical data
- Abstract
Objective: Aspiration sclerotherapy is a percutaneous procedure indicated for treatment of symptomatic simple hepatic cysts. The efficacy and safety of this procedure have been sources of debate and disagreement for years. The purpose of this study was to assess the long-term efficacy and safety of aspiration sclerotherapy in a systematic review of the literature., Materials and Methods: A systematic search was conducted of the electronic databases PubMed MEDLINE, Embase, Web of Science, and the Cochrane Library (until August 2015). Studies of proportional volume or diameter reduction after aspiration sclerotherapy of simple hepatic cysts were included for full-text evaluation. Case reports and case series were excluded. Risk of bias was assessed by use of the Newcastle-Ottawa scale., Results: From 9357 citations, 100 were selected for full-text assessment. We included 16 studies, which included 526 patients with a total of 588 treated cysts. Overall, risk of bias was high, with 12 of 16 studies having a score of poor. Proportional cyst volume reduction ranged between 76% and 100% after a median follow-up period of 1-54 months. Change in symptoms was evaluated in 10 studies: 72-100% of patients reported symptom reduction, and 56-100% reported disappearance. Postprocedural pain occurred most frequently, at a rate of 5-90% among studies. Ethanol intoxication occurred in up to 93% of cases and was reported more frequently in studies with either high ethanol volumes (133.7-138.3 mL) or long sclerotherapy duration (120-180 minutes)., Conclusion: We found excellent results with respect to long-term efficacy and safety after aspiration sclerotherapy of hepatic cysts. Nevertheless, because of the high risk of bias in the included studies, definite conclusions regarding efficacy cannot be drawn.
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- 2017
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44. Treatment Targets in Inflammatory Bowel Disease: Current Status in Daily Practice.
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Römkens TE, Gijsbers K, Kievit W, Hoentjen F, and Drenth JP
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- Adult, Colitis, Ulcerative diagnosis, Crohn Disease diagnosis, Endoscopy, Gastrointestinal, Endpoint Determination trends, Female, Health Care Surveys, Humans, Intestinal Mucosa pathology, Male, Netherlands, Predictive Value of Tests, Remission Induction, Treatment Outcome, Anti-Inflammatory Agents therapeutic use, Colitis, Ulcerative drug therapy, Crohn Disease drug therapy, Gastroenterologists trends, Gastrointestinal Agents therapeutic use, Intestinal Mucosa drug effects, Practice Patterns, Physicians' trends, Wound Healing drug effects
- Abstract
Background and Aims: Recently, treatment goals in inflammatory bowel disease (IBD) in clinical trials have shifted from mainly symptom-based to more mucosa-driven. Real world data on treatment priorities are lacking. We aimed to investigate the current practice and most commonly used definitions of IBD treatment targets among Dutch gastroenterologists., Methods: Dutch gastroenterologists were asked to participate in a computer-based nation-wide survey. We asked questions on demographics, opinion and current practice regarding IBD treatment targets., Results: Twenty-four percent (134/556) of the respondents completed the survey. For both Crohn's disease (CD) (47.3%, 61/129) and ulcerative colitis (UC)(45%, 58/129) the main treatment goal was to achieve and maintain deep remission, defined as clinical, biochemical and endoscopic remission. Seventy-six percent of the participants use mucosal healing (MH) as a potential treatment target for IBD, whereas 22.6% use histological remission. There is no single definition for MH in IBD. The majority use Mayo score ≤ 1 in UC (52%) and 'macroscopic normal mucosa' in CD (66%)., Conclusion: More stringent and mucosa-driven treatment targets as 'deep remission' and 'mucosal healing' have found traction in clinical practice. The most commonly used definition for MH in routine practice is endoscopic MAYO score = 1 in UC and 'macroscopic normal mucosa' in CD.
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- 2016
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45. Drug-Drug Interactions Between Direct-Acting Antivirals and Psychoactive Medications.
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Smolders EJ, de Kanter CT, de Knegt RJ, van der Valk M, Drenth JP, and Burger DM
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- Antiviral Agents pharmacokinetics, Antiviral Agents therapeutic use, Drug Interactions, Humans, Psychotropic Drugs pharmacokinetics, Psychotropic Drugs therapeutic use, Antiviral Agents pharmacology, Cytochrome P-450 Enzyme System drug effects, Hepatitis C, Chronic drug therapy, Mental Disorders drug therapy, Psychotropic Drugs pharmacology
- Abstract
Treatment options for chronic hepatitis C virus (HCV) infection have drastically changed since the development and licensing of new potent direct-acting antivirals (DAAs). The majority of DAAs are extensively metabolized by liver enzymes and have the ability to influence cytochrome P450 (CYP) enzymes. Additionally, these DAAs are both substrates and inhibitors of drug transporters, which makes the DAAs both possible victims or perpetrators of drug-drug interactions (DDIs). There is a high prevalence of mental illnesses such as depression or psychosis in HCV-infected patients; therefore, psychoactive medications are frequently co-administered with DAAs. The majority of these psychoactive medications are also metabolized by CYP enzymes but remarkably little information is available on DDIs between psychoactive medications and DAAs. Hence, the aim of this review is to provide an overview of the interaction mechanisms between DAAs and psychoactive agents. In addition, we describe evidenced-based interactions between DAAs and psychoactive drugs and identify safe options for the simultaneous treatment of mental illnesses and chronic HCV infection., Competing Interests: Compliance with Ethical Standards Funding No funding was used in the preparation of this review. Conflict of interest E.J. Smolders and C.T.M.M. de Kanter declare that they have no conflicts of interest that are directly relevant to the content of this review. R.J. de Knegt received sponsorship/research grants from BMS and Janssen; is a consultant for AbbVie, BMS, Gilead, Roche, and Janssen; and has delivered lectures for AbbVie, Janssen, Gilead, and Roche. J.P.H. Drenth is on the advisory boards for AbbVie, BMS, Gilead, Janssen, and Merck and received sponsorship/research grants from AbbVie and Janssen. D.M. Burger is on the advisory boards for AbbVie, BMS, Gilead, Janssen, and Merck and received sponsorship/research grants from BMS, Janssen, Merck, and Viiv. However, these conflicts of interests did not influence the preparation of this review.
- Published
- 2016
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46. Chromosomal abnormalities in hepatic cysts point to novel polycystic liver disease genes.
- Author
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Wills ES, Cnossen WR, Veltman JA, Woestenenk R, Steehouwer M, Salomon J, Te Morsche RH, Huch M, Hehir-Kwa JY, Banning MJ, Pfundt R, Roepman R, Hoischen A, and Drenth JP
- Subjects
- Adult, Aged, Aged, 80 and over, Calcium-Binding Proteins, Chromosomes, Human, X, Cysts pathology, Female, Germ-Line Mutation, Glucosidases genetics, Haploinsufficiency, Humans, Intracellular Signaling Peptides and Proteins genetics, Liver pathology, Liver Diseases pathology, Male, Middle Aged, Sex Chromosome Aberrations, Sex Chromosome Disorders of Sex Development, TRPP Cation Channels genetics, Trisomy, Chromosome Aberrations, Cysts genetics, Liver Diseases genetics, Protein Serine-Threonine Kinases genetics
- Abstract
Autosomal dominant polycystic liver disease (ADPLD) is caused by variants in PRKCSH, SEC63, and LRP5, whereas autosomal dominant polycystic kidney disease is caused by variants in PKD1 and PKD2. Liver cyst development in these disorders is explained by somatic loss-of-heterozygosity (LOH) of the wild-type allele in the developing cyst. We hypothesize that we can use this mechanism to identify novel disease genes that reside in LOH regions. In this study, we aim to map abnormal genomic regions using high-density SNP microarrays to find novel PLD genes. We collected 46 cysts from 23 patients with polycystic or sporadic hepatic cysts, and analyzed DNA from those cysts using high-resolution microarray (n=24) or Sanger sequencing (n=22). We here focused on regions of homozygosity on the autosomes (>3.0 Mb) and large CNVs (>1.0 Mb). We found frequent LOH in PRKCSH (22/29) and PKD1/PKD2 (2/3) cysts of patients with known heterozygous germline variants in the respective genes. In the total cohort, 12/23 patients harbored abnormalities outside of familiar areas. In individual ADPLD cases, we identified germline events: a 2q13 complex rearrangement resulting in BUB1 haploinsufficiency, a 47XXX karyotype, chromosome 9q copy-number loss, and LOH on chromosome 3p. The latter region was overlapping with an LOH region identified in two other cysts. Unique germline and somatic abnormalities occur frequently in and outside of known genes underlying cysts. Each liver cyst has a unique genetic makeup. LOH driver gene BUB1 may imply germline causes of genetic instability in PLD.
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- 2016
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47. Altered Pharmacokinetics of Statins Explain Increased Risk of Rhabdomyolysis in Advanced Cirrhosis.
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Weersink RA, Drenth JP, and Borgsteede SD
- Subjects
- Drug Interactions, Humans, Liver Cirrhosis, Risk, Simvastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Rhabdomyolysis
- Published
- 2016
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48. Clinical Outcomes Following a Switch from Remicade® to the Biosimilar CT-P13 in Inflammatory Bowel Disease Patients: A Prospective Observational Cohort Study.
- Author
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Smits LJ, Derikx LA, de Jong DJ, Boshuizen RS, van Esch AA, Drenth JP, and Hoentjen F
- Subjects
- Adolescent, Adult, Aged, C-Reactive Protein analysis, Colitis, Ulcerative drug therapy, Crohn Disease drug therapy, Feces chemistry, Female, Humans, Leukocyte L1 Antigen Complex analysis, Male, Middle Aged, Prospective Studies, Treatment Outcome, Young Adult, Antibodies, Monoclonal therapeutic use, Biosimilar Pharmaceuticals therapeutic use, Drug Substitution, Gastrointestinal Agents therapeutic use, Inflammatory Bowel Diseases drug therapy, Infliximab therapeutic use
- Abstract
Background and Aims: The biosimilar of Remicade®, CT-P13, recently entered the European market. Clinical data on switching from Remicade® to CT-P13 in inflammatory bowel disease [IBD] are scarce. We aimed to prospectively investigate efficacy, safety, pharmacokinetic profile, and immunogenicity following a switch from Remicade® to CT-P13 in IBD patients., Methods: Remicade®-treated IBD patients at the Radboud university medical centre who switched to CT-P13 were included in this prospective observational cohort study. Primary endpoint was change in Harvey-Bradshaw Index for Crohn's disease [CD] and Simple Clinical Colitis Activity Index for ulcerative colitis [UC] at week 16. We measured C-reactive protein [CRP], faecal calprotectin [FCP], infliximab trough level [TL] and anti-drug antibodies [ADAs] and documented adverse events., Results: Our cohort consisted of 83 patients (28 males, 57 CD, 24 UC, 2 IBD-unclassified [IBD-U]). The median age was 36 years, range 18-79. Median change in disease activity was 0 [range -23 to +7] for CD and 0 [range -3 to +6] for UC/IBD-U. Median CRP and FCP levels did not change significantly during follow-up. Median TL increased from 3.5 µg/ml [range 0-18] to 4.2 µg/ml [range 0-21] at week 16 [p = 0.010]. Two patients developed a new detectable ADA response during follow-up and five patients discontinued CT-P13. No serious adverse events occurred., Conclusions: We demonstrated that switching from Remicade® to CT-P13 in a real-life cohort of IBD patients did not have a significant impact on short-term clinical outcomes. These results suggest that switching from Remicade® to CT-P13 for the treatment of IBD is feasible., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2016
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49. Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion.
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Weersink RA, Bouma M, Burger DM, Drenth JP, Hunfeld NG, Kranenborg M, Monster-Simons MH, van Putten SA, Metselaar HJ, Taxis K, and Borgsteede SD
- Subjects
- Drug Interactions, Humans, Netherlands epidemiology, Patient Safety, Practice Guidelines as Topic, Chemical and Drug Induced Liver Injury prevention & control, Expert Testimony, Liver Cirrhosis drug therapy, Pharmaceutical Preparations administration & dosage, Prescription Drugs administration & dosage
- Abstract
Introduction: Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis., Methods and Analysis: For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population., Ethics and Dissemination: Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings., Competing Interests: DB has received research grants from BMS, MSD and ViiV and has performed teaching for Abbvie, BMS, Gilead, MSD and ViiV, outside the submitted work. JD has received research grants from Abbvie and Janssen and has been a member of advisory boards of AbbVie, BMS, Gilead, Janssen, and Merck, outside the submitted work. HM has received research grants from AbbVie, Astellas, Novartis and Gilead and has been a member of advisory boards of AbbVie, Astellas and Novartis, outside the submitted work., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
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- 2016
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50. Clinical impact of five large-scale screening projects for chronic hepatitis B in Chinese migrants in the Netherlands.
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Coenen S, van Meer S, Vrolijk JM, Richter C, van Erpecum KJ, Mostert MC, Veldhuijzen IK, Reijnders JG, van Soest H, Dirksen K, Drenth JP, Koene RP, Bosschart M, Friederich P, Ter Borg MJ, Daemen RH, Arends JE, Verhagen MA, Schout C, and Spanier BW
- Subjects
- Adult, Aged, Aged, 80 and over, Antiviral Agents therapeutic use, Asian People, China ethnology, Demography, Female, Hepatitis B Surface Antigens blood, Hepatitis B virus genetics, Hepatitis B, Chronic drug therapy, Humans, Male, Middle Aged, Netherlands epidemiology, Transients and Migrants, Young Adult, Carcinoma, Hepatocellular ethnology, Hepatitis B, Chronic ethnology, Liver Cirrhosis ethnology, Liver Neoplasms ethnology, Mass Screening methods
- Abstract
Background & Aims: In low-endemic countries it is debated whether first-generation migrants should be screened for chronic hepatitis B infection. We describe the clinical impact of five large-scale Dutch screening projects for hepatitis B in first-generation Chinese migrants., Methods: Between 2009 and 2013 five independent outreach screening projects for hepatitis B targeting first-generation Chinese migrants were conducted in five main Dutch regions. To explore the relevance of our screening we defined clinical impact as the presence of an indication for: (i) antiviral therapy, (ii) strict follow-up because of high hepatitis B DNA levels and/or (iii) surveillance for hepatocellular carcinoma., Results: In total, 4423 persons participated in the projects of whom 6.0% (n = 264) were HBsAg positive. One hundred and twenty-nine newly diagnosed HBsAg-positive patients were analysed in specialist care. Among these patients prevalence of cirrhosis was 6.9% and antiviral therapy for hepatitis B was started in 32 patients (25%). In patients without a treatment indication, strict follow-up because of high hepatitis B DNA levels and/or surveillance for hepatocellular carcinoma was considered indicated in 64 patients (50%)., Conclusions: In our screening project in first-generation Chinese migrants, antiviral treatment, strict follow-up because of high hepatitis B DNA levels and/or surveillance for hepatocellular carcinoma were considered indicated in three of four analysed HBsAg-positive patients. These data show that detection of hepatitis B in Chinese migrants can have considerable impact on patient care., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2016
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