Investigation and management of a raised serum ferritin

Serum ferritin level is one of the most commonly requested investigations in both primary and secondary care. Whilst low serum ferritin levels invariably indicate reduced iron stores, raised serum ferritin levels can be due to multiple different aetiologies, including iron overload, inflammation, liver or renal disease, malignancy, and the recently described metabolic syndrome. A key test in the further investigation of an unexpected raised serum ferritin is the serum transferrin saturation. This guideline reviews the investigation and management of a raised serum ferritin level. The investigation and management of genetic haemochromatosis is not dealt with however and is the subject of a separate guideline

Variants in PCSK7, PNPLA3 and TM6SF2 are risk factors for the development of cirrhosis in hereditary haemochromatosis

BACKGROUND: Cirrhosis develops in <10% of individuals homozygous for the C282Y variant in the homeostatic iron regulator (HFE) gene. Carriage of PCSK7:rs236918 is associated with an increased risk of cirrhosis in this population. AIM: To determine if genetic variants significantly associated with the risk of alcohol- and NAFLD-related cirrhosis also modulate the cirrhosis risk in C282Y homozygotes. METHODS: Variants in PCSK7, PNPLA3, TM6SF2, MBOAT7 and HSD17B13 were genotyped in 1319 C282Y homozygotes, from six European countries, of whom 171 (13.0%) had cirrhosis. Genotypic and allelic associations with the risk for developing cirrhosis were assessed, adjusting for age and sex. Fixed effects meta-analyses of the adjusted summary data for each country were performed. Post hoc association testing was undertaken in the 131 (76.6%) cases and 299 (26.0%) controls with available liver histology. RESULTS: Significant associations were observed between PCSK7:rs236918 (OR = 1.52 [95% CI 1.06-2.19]; P = 0.022; I2  = 0%); PNPLA3:rs738409 (OR = 1.60 [95% CI 1.22-2.11]; P = 7.37 × 10-4 ; I2  = 45.5%) and TM6SF2:rs58542926 (OR = 1.94 [95% CI 1.28-2.95]; P = 1.86 × 10-3 ; I2  = 0%) and the cirrhosis risk in C282Y homozygotes. These findings remained significant in the subpopulation with available liver histology. The population-attributable fractions were 5.6% for PCSK7:rs236918, 13.8% for PNPLA3:rs738409, 6.5% for TM6SF2:rs58542926 and 24.0% for carriage of all three variants combined. CONCLUSIONS: The risk of cirrhosis associated with carriage of PCSK7:rs236918 was confirmed in this much larger population of C282Y homozygotes. In addition, PNPLA3:rs738409 and TM6SF2:rs58542926 were established as significant additional risk factors. More detailed genetic testing of C282Y homozygotes would allow risk stratification and help guide future management

Reduction of artefacts caused by hip implants in CT-based attenuation-corrected PET images using 2-D interpolation of a virtual sinogram on an irregular grid

Metallic prosthetic replacements, such as hip or knee implants, are known to cause strong streaking artefacts in CT images. These artefacts likely induce over- or underestimation of the activity concentration near the metallic implants when applying CT-based attenuation correction of positron emission tomography (PET) images. Since this degrades the diagnostic quality of the images, metal artefact reduction (MAR) prior to attenuation correction is required

Diagnosis and therapy of genetic haemochromatosis (review and 2017 update)

Genetic haemochromatosis (GH) is one of the most frequentgenetic disorders found in Northern Europeans. GH is a condition caused by continued absorption of iron from the upper small intestine, despite normal, and then increased, total body iron. This leads to accumulation of iron in the tissues as the body has no means of getting rid of excess iron.In advanced disease, iron accumulation causes widespread tissue damage, including diabetes mellitus and cirrhosis. The disorder is inherited in autosomal recessive fashion. The gene involved lies close to the HLA-A region on chromosome 6. This updated guideline follows on from the previously published guideline commissioned by the British Committee forStandards in Haematology in February 2000 (Dooley & Wor-wood, 2000). This review and updated guidance coincides with the development of a separate guideline on the investigation and management of a raised serum ferritin, also commissioned by the BSH guidelines committee

The autonomic nervous system

The autonomic nervous system innervates the visceral organs, the glands and the blood vessels. It regulates the internal environment, and it is largely responsible for maintaining normal bodily functions such as respiration, blood pressure and micturition. The peripheral autonomic nervous system consists of two parts, a thoracolumbar or sympathetic and a craniosacral or parasympathetic division, which usually have antagonistic effects (Sect. 12.2). The sympathetic system is organized to mobilize the body for activities, especially in stressful situations (Cannon’s fight or flight), whereas the parasympathetic system in particular stimulates the peristaltic and secretory activities of the gastrointestinal tract (also known as rest and digest response). The peripheral part of the autonomic nervous system includes neurons in the viscera and peripheral ganglia, which are innervated by the lateral horn of the spinal cord and certain brain stem nuclei. Neuronal plexuses in the gastrointestinal tract form the enteric nervous system, which is often viewed as the third component of the autonomic nervous system. Tonically active bulbar centres control vital functions such as blood pressure and respiration. The autonomic centres in the brain stem and spinal cord are reciprocally connected with the central autonomic network (Sect. 12.3), which includes the hypothalamus and several other forebrain (in particular the extended amygdala and the insula) and brain stem structures such as the periaqueductal grey and the parabrachial nucleus. This network is essential for the integration of autonomic, endocrine and somatomotor functions. The peripheral and central autonomic pathways may be affected by many diseases, which cause derangement of autonomic functions as exemplified in several Clinical Cases on disorders of the neural control of blood pressure, breathing and micturition. The English terms of the Terminologia Neuroanatomica are used throughout