Long-term safety of withholding standard prophylaxis in patients with moderate chronic kidney disease.

In the latest ESUR contrast media guidelines, standard prophylaxis is no longer recommended for patients with moderate chronic kidney disease (CKD). In the absence of solid evidence, guideline updates are often based on indirect evidence and expert opinion. Likewise, evidence supporting the withdrawal of standard prophylaxis in moderate CKD patients was scarce and mostly indirect, but did include one randomised controlled trial evaluating guideline-recommended standard prophylactic intravenous hydration against a group receiving no prophylaxis (A MAastricht Contrast-Induced Nephropathy Guideline (AMACING) trial). Since then, benefits of the updated guideline recommendation for patient and hospital burden have been numerated and were shown to be substantial. The current special report provides data on long-term safety from the AMACING randomised controlled trial. KEY POINTS: • In the latest version of ESUR clinical practice guidelines for safe use of contrast media, standard prophylaxis is no longer recommended for patients with moderate chronic kidney disease. • Benefits of this change in recommendations for patient and hospital burden have been numerated. The current report provides data on long-term safety from the AMACING randomised controlled trial. • No disadvantage of withholding prophylaxis could be discerned. Results suggest that, in this population, underlying disease is more relevant for survival and prognosis than contrast administration itself.

Impact on clinical practice of updated guidelines on iodinated contrast material: CINART.

OBJECTIVE: Guidelines on safe use of iodinated contrast material recommend intravenous prophylactic hydration to prevent post-contrast adverse (renal) effects. Recently, guidelines have been updated and standard prophylaxis is no longer recommended for the majority of patients. The current study aims to evaluate the consequences for clinical practice of the updated guidelines in terms of complications, hospitalisations, and costs. METHODS: The Contrast-Induced Nephropathy After Reduction of the prophylaxis Threshold (CINART) project is a retrospective observational study. All elective procedures with intravascular iodinated contrast administration at Maastricht University Medical Centre (UMC+) in patients aged > 18 years, formerly eligible for prophylaxis (eGFR 30-44 ml/min/1.73 m2 or eGFR 45-59 ml/min/1.73 m2 in combination with diabetes or > 1 predefined risk factor), and currently eligible for prophylaxis (eGFR < 30 ml/min/1.73 m2) were included. Data were used to calculate relative reductions in complications, hospitalisations, and costs associated with standard prophylactic intravenous hydration. CINART is registered with Clinicaltrials.gov: NCT03227835. RESULTS: Between July 1, 2017, and July 1, 2018, 1992 elective procedures with intravascular iodinated contrast in patients formerly and currently eligible for prophylaxis were identified: 1808 in patients formerly eligible for prophylaxis and 184 in patients currently eligible for prophylaxis. At Maastricht UMC+, guideline updates led to large relative reductions in numbers of complications of prophylaxis (e.g. symptomatic heart failure; - 89%), extra hospitalisations (- 93%), and costs (- 91%). CONCLUSION: Guideline updates have had a demonstrable impact on daily clinical practice benefiting patient, hospital, and health care budgets. Clinical practice varies between institutions and countries; therefore, a local estimation model is provided with which local impact on costs, hospitalisations, and complications can be calculated. KEY POINTS: • Clinical practice guidelines recommend prophylactic intravenous hydration to prevent post-contrast adverse outcomes such as contrast-induced acute kidney injury. • Clinical practice guidelines have recently been updated, and standard prophylaxis is no longer recommended for the majority of patients. • The guideline updates have a large impact on daily clinical practice: relative reductions at Maastricht UMC+ were - 89% prophylaxis complications, - 93% hospitalisations, and - 91% costs, and similar reductions are expected for Dutch and adherent European medical centres.

[Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial]. / Preventieve intraveneuze hydratie ter voorkoming van contrastnefropathie helpt niet.

BACKGROUND: Intravenous saline is recommended in clinical practice guidelines as the cornerstone for preventing contrast-induced nephropathy in patients with compromised renal function. However, clinical-effectiveness and cost-effectiveness of this prophylactic hydration treatment in protecting renal function has not been adequately studied in the population targeted by the guidelines, against a group receiving no prophylaxis. This was the aim of the AMACING trial. METHODS: AMACING is a prospective, randomised, phase 3, parallel-group, open-label, non-inferiority trial of patients at risk of contrast-induced nephropathy according to current guidelines. High-risk patients (with an estimated glomerular filtration rate [eGFR] of 30-59 mL per min/1·73 m²) aged 18 years and older, undergoing an elective procedure requiring iodinated contrast material administration at Maastricht University Medical Centre, the Netherlands, were randomly assigned (1:1) to receive intravenous 0·9% NaCl or no prophylaxis. We excluded patients with eGFR lower than 30 mL per min/1·73 m², previous dialysis, or no referral for intravenous hydration. Randomisation was stratified by predefined risk factors. The primary outcome was incidence of contrast-induced nephropathy, defined as an increase in serum creatinine from baseline of more than 25% or 44 µmol/L within 2-6 days of contrast exposure, and cost-effectiveness of no prophylaxis compared with intravenous hydration in the prevention of contrast-induced nephropathy. We measured serum creatinine immediately before, 2-6 days, and 26-35 days after contrast-material exposure. Laboratory personnel were masked to treatment allocation. Adverse events and use of resources were systematically recorded. The non-inferiority margin was set at 2·1%. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT02106234. FINDINGS: Between June 17, 2014, and July 17, 2016, 660 consecutive patients were randomly assigned to receive no prophylaxis (n=332) or intravenous hydration (n=328). 2-6 day serum creatinine was available for 307 (92%) of 332 patients in the no prophylaxis group and 296 (90%) of 328 patients in the intravenous hydration group. Contrast-induced nephropathy was recorded in eight (2·6%) of 307 non-hydrated patients and in eight (2·7%) of 296 hydrated patients. The absolute difference (no hydration vs hydration) was -0·10% (one-sided 95% CI -2·25 to 2·06; one-tailed p=0·4710). No hydration was cost-saving relative to hydration. No haemodialysis or related deaths occurred within 35 days. 18 (5·5%) of 328 patients had complications associated with intravenous hydration. INTERPRETATION: We found no prophylaxis to be non-inferior and cost-saving in preventing contrast-induced nephropathy compared with intravenous hydration according to current clinical practice guidelines.

[Real change or natural fluctuation?] / Echte verandering of natuurlijke schommeling?

When monitoring patients over time, it may be difficult to distinguish 'real changes' from so-called 'natural fluctuations' when interpreting consecutive laboratory results. Consider a patient whose cholesterol level has decreased from a baseline 6.6 mmol/L to 6.1 mmol/L six months after receiving lifestyle advice. How likely is it that this is a 'real change', reflecting a lifestyle change, rather than random fluctuation? Physicians mostly rely on their intuition and clinical experience when interpreting changes in consecutive laboratory results. For inexperienced physicians, the lack of an easy reference for the interpretation of consecutive laboratory results can make decision-making challenging. We have developed the medical/educational smartphone app Labtracker+ that calculates the probability of a 'real change' between two consecutive laboratory results, using biological variation data from scientific literature and analytical precision that is achieved in contemporary laboratories. This approach may complement intuitive, experience-based interpretations of consecutive laboratory results.

A case of thymoma-associated autoimmune haemolytic anaemia.

A 50-year-old female presented with severe Coombs-positive haemolytic anaemia. Chest roentgenogram revealed a right-sided paracardial mass in the anterior mediastinum that was proven to be a thymoma. The patient was treated with oral prednisone (1 mg/kg/day) and subsequent thymectomy. Haemolysis did not return although the direct Coombs test remained weakly positive. In reviewing the literature 15 additional cases of thymoma-associated autoimmune haemolytic anaemia were identified.

Pneumatosis cystoides intestinalis, four cases of a rare disease.

Pneumatosis cystoides intestinalis (PCI) is a disease in which small gas-filled cysts appear in the intestinal wall. Four cases presented here demonstrate the diversity of the associated diseases. In two of the patients constipation probably played a role; in the third patient decreased colonic motility, elevated intestinal pressure and increased mucosal permeability in the context of enteritis treated with codeine was the underlying problem; in the fourth high protein feeding and bowel ischaemia was diagnosed. Various aetiologies are presented in the literature. There is no specific history and physical or laboratory findings do not help to diagnose PCI. Plain abdominal film, ultrasound, computer tomography, magnetic resonance imaging, barium contrast studies and/or endoscopy may be necessary for diagnosis. Therapy is based on enhancing partial oxygen pressure in the bowel wall. PCI usually runs a benign course.

[Empty sella syndrome as the cause of panhypopituitarism]. / Het 'empty sella'-syndroom als oorzaak van panhypopituïtarisme.

In two patients, men aged 78 and 42 years respectively, an empty-sella syndrome was found. The first patient presented with chronic fatigue, in the second the empty sella was the late result of prior neurosurgery followed by external irradiation. Both suffered from panhypopituitarism. In both cases the diagnosis was confirmed following laboratory tests and MRI. Hormone-replacement therapy was found to provide adequate treatment. The course of the empty-sella syndrome is usually benign and with adequate hormone-replacement therapy a good quality of life is maintained.

Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis.

BACKGROUND: Several imaging techniques may reveal calcification of the arterial wall or cardiac valves. Many studies indicate that the risk for cardiovascular disease is increased when calcification is present. Recent meta-analyses on coronary calcification and cardiovascular risk may be confounded by indication. Therefore, this meta-analysis was performed with extensive subgroup analysis to assess the overall cardiovascular risk of finding calcification in any arterial wall or cardiac valve when using different imaging techniques. METHODS AND RESULTS: A meta-analysis of prospective studies reporting calcifications and cardiovascular end-points was performed. Thirty articles were selected. The overall odds ratios (95% confidence interval [CI]) for calcifications versus no calcifications in 218,080 subjects after a mean follow-up of 10.1 years amounted to 4.62 (CI 2.24 to 9.53) for all cause mortality, 3.94 (CI 2.39 to 6.50) for cardiovascular mortality, 3.74 (CI 2.56 to 5.45) for coronary events, 2.21 (CI 1.81 to 2.69) for stroke, and 3.41 (CI 2.71 to 4.30) for any cardiovascular event. Heterogeneity was largely explained by length of follow up and sort of imaging technique. Subgroup analysis of patients with end stage renal disease revealed a much higher odds ratio for any event of 6.22 (CI 2.73 to 14.14). CONCLUSION: The presence of calcification in any arterial wall is associated with a 3-4-fold higher risk for mortality and cardiovascular events. Interpretation of the pooled estimates has to be done with caution because of heterogeneity across studies.