Database : MEDLINE
Search on : hypophosphatemia [Words]
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[PMID]: 29520435
[Au] Autor:El-Khoueiry AB; O'Donnell R; Semrad TJ; Mack P; Blanchard S; Bahary N; Jiang Y; Yen Y; Wright J; Chen H; Lenz HJ; Gandara DR
[Ad] Address:University of Southern California Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Suite 3459, Los Angeles, CA, 90089, USA. elkhouei@med.usc.edu.
[Ti] Title:A phase I trial of escalating doses of cixutumumab (IMC-A12) and sorafenib in the treatment of advanced hepatocellular carcinoma.
[So] Source:Cancer Chemother Pharmacol;, 2018 Mar 08.
[Is] ISSN:1432-0843
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:PURPOSE: The insulin-like growth factor (IGF) pathway is activated in hepatocarcinogenesis. Cixutumumab is a monoclonal antibody against human insulin-like growth factor-1 receptor (IGF-1R). Given the cross-talk between the IGF and VEGF pathways, we performed a phase I study of the combination of cixutumumab and sorafenib in hepatocellular cancer (HCC). METHODS: Eligible patients with no prior systemic therapy for advanced HCC and Child-Pugh A to B7 were treated with sorafenib 400 mg BID and escalating doses of cixutumumab (2, 4, or 6 mg/kg IV weekly) in a 3 + 3 design. Dose limiting toxicity (DLT) was defined as treatment-related grade 3 or 4 non-hematologic toxicity (except for a subset of manageable toxicities) or any grade 4 hematologic toxicities. RESULTS: In 21 patients enrolled, there were 3 DLTs; grade 3 hyperglycemia, grade 3 hypophosphatemia, and grade 5 peritonitis. The maximum tolerated dose of cixutumumab was 4 mg/kg IV weekly with standard dose sorafenib. Eighteen of 21 (86%) patients had grade 3 or above toxicities attributed to treatment. One patient also experienced grade 4 colonic perforation and grade 5 peritonitis. The median number of cycles completed was 4 (0-26). Of 16 patients evaluable for response, 81% achieved stable disease. The median progression free survival was 6.0 months (95% CI 3.6-undefined) and the median overall survival was 10.5 months (95% CI 7.1-undefined). CONCLUSIONS: While the combination of cixutumumab and sorafenib had a toxicity profile similar to that of sorafenib monotherapy, it manifested limited clinical efficacy in unselected patients with HCC.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1007/s00280-018-3553-4

  2 / 5027 MEDLINE  
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[PMID]: 29519205
[Au] Autor:Miller CJ; Doepker BA; Springer AN; Exline MC; Phillips G; Murphy CV
[Ad] Address:1 Department of Pharmacy, University of Colorado Hospital, Aurora, CO, USA.
[Ti] Title:Impact of Serum Phosphate in Mechanically Ventilated Patients With Severe Sepsis and Septic Shock.
[So] Source:J Intensive Care Med;:885066618762753, 2018 Jan 01.
[Is] ISSN:1525-1489
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Hypo- and hyperphosphatemia are common in severe sepsis and septic shock. Published outcome data in patients with phosphate derangements primarily focus on hypophosphatemia and the general critically ill population. This study aimed to determine the impact of serum phosphate on clinical outcomes in patients with severe sepsis and septic shock. METHODS: A retrospective cohort analysis of adult mechanically ventilated patients with severe sepsis or septic shock was performed. Patients were randomly selected from an internal intensive care unit (ICU) database at an academic medical center in the United States and screened for inclusion and exclusion criteria. Time-weighted phosphate was calculated using all phosphate measurements obtained during ICU admission. The associations between time-weighted phosphate and duration of mechanical ventilation, 28-day mortality, and ICU and hospital length of stay were evaluated using linear or logistic regression as appropriate. RESULTS: One-hundred ninety-seven patients were evaluated: 33 were categorized as hypophosphatemia, 123 as normophosphatemia, and 41 as hyperphosphatemia. Patients with time-weighted hyperphosphatemia had a higher Simplified Acute Physiology Score III score and incidence of septic shock. Significantly higher rates of 28-day mortality were observed among those with time-weighted phosphate levels above 3.5 mg/dL. However, both time-weighted hypo- and hyperphosphatemia were associated with decreased duration of mechanical ventilation. For every 0.5 mg/dL increase in time-weighted phosphate referent values from 4.0 to 6.0, the duration of mechanical ventilation decreased by 8% to 26%. For every 0.5 mg/dL decrease in time-weighted phosphate referent values from 3.0 to 1.0, significant decreases in duration of mechanical ventilation ranged from 14% to 41%. CONCLUSION: Time-weighted hyperphosphatemia may be associated with increased mortality in mechanically ventilated patients with severe sepsis or septic shock. However, time-weighted hypo- and hyperphosphatemia were associated with decreased duration of mechanical ventilation. Future studies should further describe the impact of hypo- and hyperphosphatemia on clinical outcomes among critically ill patients with severe sepsis or septic shock.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1177/0885066618762753

  3 / 5027 MEDLINE  
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[PMID]: 29383408
[Au] Autor:Sullivan R; Abraham A; Simpson C; Olear E; Carpenter T; Deng Y; Chen C; Insogna KL
[Ad] Address:Department of Medicine, Section of Endocrinology, Yale School of Medicine, New Haven, CT, USA.
[Ti] Title:Three-Month Randomized Clinical Trial of Nasal Calcitonin in Adults with X-linked Hypophosphatemia.
[So] Source:Calcif Tissue Int;, 2018 Jan 30.
[Is] ISSN:1432-0827
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Previous work has demonstrated that a single subcutaneous dose of salmon calcitonin leads to a transient decline in circulating levels of FGF23 in patients with X-linked hypophosphatemia (XLH). Since the calcitonin receptor is expressed on osteocytes, this raises the possibility that interdicting signals through that receptor could modulate circulating levels of FGF23 in XLH. In the present study, 21 subjects with XLH were randomly assigned to receive either placebo nasal spray or 400 IU of nasal salmon calcitonin daily for three months. On the first and last day of the study, serial measurements of FGF23, 1,25-dihydroxyvitamin D, and TmP/GFR were made over 27 h. At the beginning of Visit 2 (the first day of month 2) and the beginning of Visit 3 (the first day of month 3), single, first-morning, fasting measurements of these same parameters were made before the next administered dose of study drug. Following the initial or final dose of study drug, there were no differences in area under the curve, based on treatment assignment, for the three principal outcome variables. Similarly, there were no differences in the fasting measures taken at the beginning of Visit 2 or Visit 3 compared to the fasting values on either day 2 of Visit 1 or the fasting values on day 2 of Visit 4. There were also no significant changes over time in serum phosphorus, serum calcium, circulating levels of PTH, CTx, or P1NP. The reasons why nasal salmon calcitonin did not recapitulate the findings with subcutaneously administered drug may relate to the kinetics of drug delivery, the bioavailability of drug or peak drug dose achieved. It remains possible, however, that other means of altering calcitonin receptor signaling may still provide an opportunity for regulating FGF23 production.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1007/s00223-017-0382-0

  4 / 5027 MEDLINE  
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[PMID]: 29505567
[Au] Autor:Acar S; BinEssa HA; Demir K; Al-Rijjal RA; Zou M; Çatli G; Anik A; Al-Enezi AF; Özisik S; Al-Faham MSA; Abaci A; Dündar B; Kattan WE; Alsagob M; Kavukçu S; Tamimi HE; Meyer BF; Böber E; Shi Y
[Ad] Address:Division of Pediatric Endocrinology, Dokuz Eylul University School of Medicine, Izmir, Turkey.
[Ti] Title:Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3.
[So] Source:PLoS One;13(3):e0193388, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Hereditary hypophosphatemia is a group of rare renal phosphate wasting disorders. The diagnosis is based on clinical, radiological, and biochemical features, and may require genetic testing to be confirmed. METHODOLOGY: Clinical features and mutation spectrum were investigated in patients with hereditary hypophosphatemia. Genomic DNA of 23 patients from 15 unrelated families were screened sequentially by PCR-sequencing analysis for mutations in the following genes: PHEX, FGF23, DMP1, ENPP1, CLCN5, SLC34A3 and SLC34A1. CytoScan HD Array was used to identify large deletions. RESULTS: Genetic evaluation resulted in the identification of an additional asymptomatic but intermittent hypophosphatemic subject. Mutations were detected in 21 patients and an asymptomatic sibling from 13 families (86.6%, 13/15). PHEX mutations were identified in 20 patients from 12 families. Six of them were novel mutations present in 9 patients: c.983_987dupCTACC, c.1586+2T>G, c.1206delA, c.436+1G>T, c.1217G>T, and g.22,215,887-22,395,767del (179880 bp deletion including exon 16-22 and ZNF645). Six previously reported mutations were found in 11 patients. Among 12 different PHEX mutations, 6 were de novo mutations. Patients with de novo PHEX mutations often had delayed diagnosis and significantly shorter in height than those who had inherited PHEX mutations. Novel compound heterozygous mutations in SLC34A3 were found in one patient and his asymptomatic sister: c.1335+2T>A and c.1639_1652del14. No mutation was detected in two families. CONCLUSIONS: This is the largest familial study on Turkish patients with hereditary hypophosphatemia. PHEX mutations, including various novel and de novo variants, are the most common genetic defect. More attention should be paid to hypophosphatemia by clinicians since some cases remain undiagnosed both during childhood and adulthood.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0193388

  5 / 5027 MEDLINE  
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[PMID]: 29314243
[Au] Autor:Bartko J; Roschger P; Zandieh S; Brehm A; Zwerina J; Klaushofer K
[Ad] Address:Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
[Ti] Title:Reply: Hypophosphatemia, Severe Bone Pain, Gait Disturbance, and Fatigue Fractures After Iron Substitution in Inflammatory Bowel Disease: A Case Report.
[So] Source:J Bone Miner Res;33(3):546, 2018 Mar.
[Is] ISSN:1523-4681
[Cp] Country of publication:United States
[La] Language:eng
[Pt] Publication type:LETTER
[Em] Entry month:1801
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:In-Data-Review
[do] DOI:10.1002/jbmr.3373

  6 / 5027 MEDLINE  
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[PMID]: 29281128
[Au] Autor:Tournis S; Michopoulos S; Makris K; Terpos E
[Ad] Address:Laboratory for Research of the Musculoskeletal System 'Th. Garofalidis', KAT Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
[Ti] Title:Re: Hypophosphatemia, Severe Bone Pain, Gait Disturbance, and Fatigue Fractures After Iron Substitution in Inflammatory Bowel Disease: A Case Report.
[So] Source:J Bone Miner Res;33(3):543-545, 2018 Mar.
[Is] ISSN:1523-4681
[Cp] Country of publication:United States
[La] Language:eng
[Pt] Publication type:LETTER
[Em] Entry month:1712
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:In-Data-Review
[do] DOI:10.1002/jbmr.3372

  7 / 5027 MEDLINE  
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[PMID]: 29502359
[Au] Autor:Xiao L; Homer-Bouthiette C; Hurley MM
[Ad] Address:Department of Medicine, University of Connecticut School of Medicine, UCONN Health, Farmington, Connecticut, 06030-052.
[Ti] Title:FGF23 Neutralizing Antibody Partially Improves Bone Mineralization Defect of HMWFGF2 Isoforms Transgenic Female Mice.
[So] Source:J Bone Miner Res;, 2018 Mar 04.
[Is] ISSN:1523-4681
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Mice overexpressing high molecular weight FGF2 isoforms (HMWTg) in osteoblast lineage phenocopy human X-linked hypophosphatemic rickets (XLH) and Hyp murine model of XLH demonstrating increased FGF23/FGF receptor signaling and hypophosphatemic rickets/osteomalacia. Since HMWFGF2 was up-regulated in bones of Hyp mice and abnormal FGF23 signaling is important in XLH, HMWTg mice were used to examine the effect of the FGF23 neutralizing antibody (FGF23Ab). Eight-week-old female Vector control mice and HMWTg mice were treated with FGF23Ab or control IgG. Single injection of FGF23Ab rescued abnormal hypophosphatemia in HMWTg. The decreased Npt2a was rescued by FGF23Ab treatment. Inappropriately low serum 1,25(OH) D in HMWTg mice was normalized by FGF23Ab treatment which is accompanied by increased anabolic vitamin D hydroxylase Cyp27b1, and decreased catabolic vitamin D hydroxylase Cyp24 mRNA in kidney. Long-term treatment with FGF23Ab normalized femur length and significantly increased vertebrae BMD and BMC, and femur BMC in HMWTg mice compared to IgG treated HMWTg mice. Micro-CT revealed increased cortical porosity and decreased cortical apparent density in HMWTg-IgG group compared with Vector-IgG group, however, FGF23Ab treatment rescued defective cortical mineralization, decreased porosity and increased apparent density in HMWTg mice. Bone histomorphometry analysis showed FGF23Ab treatment decreased osteoid volume, increased intra label thickness, mineralization apposition rate and bone formation rate in HMWTg mice. FGF23Ab improved disorganized double labeling in femur from HMWTg mice. Quantitative real time PCR analysis of tibiae shaft showed FGF23 Ab treatment normalized the Ocn mRNA expression in HMWTg mice, but further increased SIBLING protein and pyrophosphate related genes expression that are important in matrix mineralization, suggesting HMWFGF2 modulates these genes independent of FGF23. We conclude that FGF23Ab partially rescued hypophosphatemic osteomalacia in HMWTg. However, long-term treatment with FGF23Ab further increased SIBLING protein related genes and pyrophosphate related genes in bone that could contribute to incomplete rescue of the mineralization defect. This article is protected by copyright. All rights reserved.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180304
[Lr] Last revision date:180304
[St] Status:Publisher
[do] DOI:10.1002/jbmr.3417

  8 / 5027 MEDLINE  
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[PMID]: 29484344
[Au] Autor:Pourhassan M; Cuvelier I; Gehrke I; Marburger C; Modreker MK; Volkert D; Willschrei HP; Wirth R
[Ad] Address:Maryam Pourhassan, Department of Geriatric Medicine, Marien Hospital Herne, Ruhr-University Bochum, Germany, Hölkeskampring 40, D- 44625 Herne, Germany, maryam.pourhassan@ruhr-uni-bochum.de.
[Ti] Title:Prevalence of Risk Factors for the Refeeding Syndrome in Older Hospitalized Patients.
[So] Source:J Nutr Health Aging;22(3):321-327, 2018.
[Is] ISSN:1760-4788
[Cp] Country of publication:France
[La] Language:eng
[Ab] Abstract:OBJECTIVES: The incidence of refeeding syndrome (RFS) in older patients is not well-known. The aim of the study was to determine the prevalence of known risk factors for RFS in older individuals during hospitalization at geriatric hospital departments. DESIGN AND SETTING: 342 consecutive older participants (222 females) who admitted at acute geriatric hospital wards were included in a cross-sectional study. We applied the National Institute for Health and Clinical Excellence (NICE) criteria for determining patients at risk of RFS. In addition, Mini Nutritional Assessment Short Form (MNA®-SF) was used to identify patients at risk of malnutrition. Weight and height were assessed. The degree of weight loss was obtained by interview. Serum phosphate, magnesium, potassium, sodium, calcium, creatinine and urea were analyzed according to standard procedures. RESULTS: Of 342 older participants included in the study (mean age 83.1 ± 6.8, BMI range of 14.7-43.6 kg/m2), 239 (69.9%) were considered to be at risk of RFS, in which 43.5% and 11.7% were at risk of malnutrition and malnourished, respectively, according to MNA-SF. Patients in the risk group had significantly higher weight loss, lower phosphate and magnesium levels. In a multivariate logistic regression analysis, low levels of phosphate and magnesium followed by weight loss were the major risk factors for fulfilling the NICE criteria. CONCLUSION: The incidence of risk factors for RFS was relatively high in older individuals acutely admitted in geriatric hospital units, suggesting that, RFS maybe more frequent among older persons than we are aware of. Patients with low serum levels of phosphate and magnesium and higher weight loss are at increased risk of RFS. The clinical characteristics of the older participants at risk of RFS indicate that these patients had a relatively poor nutritional status which can help us better understand the potential scale of RFS on admission or during the hospital stay.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Data-Review
[do] DOI:10.1007/s12603-017-0917-0

  9 / 5027 MEDLINE  
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[PMID]: 29401002
[Au] Autor:Juric D; Rodon J; Tabernero J; Janku F; Burris HA; Schellens JHM; Middleton MR; Berlin J; Schuler M; Gil-Martin M; Rugo HS; Seggewiss-Bernhardt R; Huang A; Bootle D; Demanse D; Blumenstein L; Coughlin C; Quadt C; Baselga J
[Ad] Address:Dejan Juric, Massachusetts General Hospital Cancer Center, Boston; Alan Huang, Novartis Institutes for BioMedical Research, Cambridge, MA; Jordi Rodon and Josep Tabernero, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona; Marta Gil-Martin, Catalan Instit
[Ti] Title:Phosphatidylinositol 3-Kinase α-Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study.
[So] Source:J Clin Oncol;:JCO2017727107, 2018 Feb 05.
[Is] ISSN:1527-7755
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Purpose We report the first-in-human phase Ia study to our knowledge ( ClinicalTrials.gov identifier: NCT01219699) identifying the maximum tolerated dose and assessing safety and preliminary efficacy of single-agent alpelisib (BYL719), an oral phosphatidylinositol 3-kinase α (PI3Kα)-selective inhibitor. Patients and Methods In the dose-escalation phase, patients with PIK3CA-altered advanced solid tumors received once-daily or twice-daily oral alpelisib on a continuous schedule. In the dose-expansion phase, patients with PIK3CA-altered solid tumors and PIK3CA-wild-type, estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer received alpelisib 400 mg once daily. Results One hundred thirty-four patients received treatment. Alpelisib maximum tolerated doses were established as 400 mg once daily and 150 mg twice daily. Nine patients (13.2%) in the dose-escalation phase had dose-limiting toxicities of hyperglycemia (n = 6), nausea (n = 2), and both hyperglycemia and hypophosphatemia (n = 1). Frequent all-grade, treatment-related adverse events included hyperglycemia (51.5%), nausea (50.0%), decreased appetite (41.8%), diarrhea (40.3%), and vomiting (31.3%). Alpelisib was rapidly absorbed; half-life was 7.6 hours at 400 mg once daily with minimal accumulation. Objective tumor responses were observed at doses ≥ 270 mg once daily; overall response rate was 6.0% (n = 8; one patient with endometrial cancer had a complete response, and seven patients with cervical, breast, endometrial, colon, and rectal cancers had partial responses). Stable disease was achieved in 70 (52.2%) patients and was maintained > 24 weeks in 13 (9.7%) patients; disease control rate (complete and partial responses and stable disease) was 58.2%. In patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer, median progression-free survival was 5.5 months. Frequently mutated genes (≥ 10% tumors) included TP53 (51.3%), APC (23.7%), KRAS (22.4%), ARID1A (13.2%), and FBXW7 (10.5%). Conclusion Alpelisib demonstrated a tolerable safety profile and encouraging preliminary activity in patients with PIK3CA-altered solid tumors, supporting the rationale for selective PI3Kα inhibition in combination with other agents for the treatment of PIK3CA-mutant tumors.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[Cl] Clinical Trial:ClinicalTrial
[St] Status:Publisher
[do] DOI:10.1200/JCO.2017.72.7107

  10 / 5027 MEDLINE  
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[PMID]: 29500574
[Au] Autor:Wirth R; Diekmann R; Janssen G; Fleiter O; Fricke L; Kreilkamp A; Modreker MK; Marburger C; Nels S; Pourhassan M; Schaefer R; Willschrei HP; Volkert D; Arbeitsgruppe Ernährung und Stoffwechsel der Deutschen Gesellschaft für Geriatrie (DGG)
[Ad] Address:Klinik für Altersmedizin und Frührehabilitation, Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Hölkeskampring 40, 44625, Herne, Deutschland. rainer.wirth@elisabethgruppe.de.
[Ti] Title:Refeeding-Syndrom : Pathophysiologie, Risikofaktoren, Prophylaxe und Therapie. [Refeeding syndrome : Pathophysiology, risk factors, prevention, and treatment].
[So] Source:Internist (Berl);, 2018 Mar 02.
[Is] ISSN:1432-1289
[Cp] Country of publication:Germany
[La] Language:ger
[Ab] Abstract:Refeeding syndrome is a life-threatening complication that may occur after initiation of nutritional therapy in malnourished patients, as well as after periods of fasting and hunger. Refeeding syndrome can be effectively prevented and treated if its risk factors and pathophysiology are known. The initial measurement of thiamine level and serum electrolytes, including phosphate and magnesium, their supplementation if necessary, and a slow increase in nutritional intake along with close monitoring of serum electrolytes play an important role. Since refeeding syndrome is not well known and the symptoms can be extremely heterogeneous, this complication is poorly recognized, especially against the background of severe disease and multimorbidity. This overview aims to summarize the current knowledge and increase awareness about refeeding syndrome.
[Pt] Publication type:ENGLISH ABSTRACT; JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180303
[Lr] Last revision date:180303
[St] Status:Publisher
[do] DOI:10.1007/s00108-018-0399-0


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