A man in his seventies with fatigue and renal failure. / En mann i 70-årene med utmattelse og nyresvikt.

A man in his seventies underwent routine heart examinations as part of workup for kidney transplantation. Unexpected findings led to more extensive investigations and revealed two rare systemic diseases as causes of his heart failure.

Bone scintigraphy reduces the need for biopsy in suspected cardiac amyloidosis. / Skjelettscintigrafi reduserer behovet for biopsi ved mistanke om kardial amyloidose.

The gold standard to diagnose suspected cardiac amyloidosis is myocardial biopsy. In recent years, bone scintigraphy has partly replaced myocardial biopsy.

Complications and mortality among patients hospitalised with COVID-19. / Komplikasjoner og dødelighet blant pasienter innlagt med covid-19.

BACKGROUND: The course of disease, complications and hospital mortality among patients with COVID-19 admitted to Norwegian hospitals has not been widely described. The purpose of this study was to survey patients with COVID-19 admitted to a local hospital. MATERIAL AND METHOD: The data were retrieved from a prospective observational study of all patients admitted with COVID-19 to Bærum Hospital since the start of the coronavirus outbreak. RESULTS: A total of 73 patients with COVID-19 admitted in the period 9 March 2020-7 May 2020 were included. The mean age was 67.9 years, and 43 patients (59 %) were men. The average number of days hospitalised was 10.1. Altogether 19 patients (26 %) had a very severe course of disease, and 14 (19 %) died during their stay in hospital. The mean age among the patients who died was 79.5 years. A total of 49 patients (67 %) had hypoxaemia and required oxygen therapy for an average of 10.1 days. Of these, 9 patients were given invasive respiratory support for a median 18 days. Symptoms of delirium occurred in 26 patients (36 %) and was the most frequent non-respiratory complication. INTERPRETATION: The majority of the patients hospitalised with COVID-19 needed prolonged oxygen therapy, and there was a high incidence of severe complications.

Cancer risk with folic acid supplements: a systematic review and meta-analysis.

Objective To explore if there is an increased cancer risk associated with folic acid supplements given orally. Design Systematic review and meta-analysis of controlled studies of folic acid supplementation in humans reporting cancer incidence and/or cancer mortality. Studies on folic acid fortification of foods were not included. Data sources Cochrane Library, Medline, Embase and Centre of Reviews and Dissemination, clinical trial registries and hand-searching of key journals. Results From 4104 potential references, 19 studies contributed data to our meta-analyses, including 12 randomised controlled trials (RCTs). Meta-analysis of the 10 RCTs reporting overall cancer incidence (N=38 233) gave an RR of developing cancer in patients randomised to folic acid supplements of 1.07 (95% CI 1.00 to 1.14) compared to controls. Overall cancer incidence was not reported in the seven observational studies. Meta-analyses of six RCTs reporting prostate cancer incidence showed an RR of prostate cancer of 1.24 (95% CI 1.03 to 1.49) for the men receiving folic acid compared to controls. No significant difference in cancer incidence was shown between groups receiving folic acid and placebo/control group, for any other cancer type. Total cancer mortality was reported in six RCTs, and a meta-analysis of these did not show any significant difference in cancer mortality in folic acid supplemented groups compared to controls (RR 1.09, 95% CI 0.90 to 1.30). None of the observational studies addressed mortality. Conclusions A meta-analysis of 10 RCTs showed a borderline significant increase in frequency of overall cancer in the folic acid group compared to controls. Overall cancer incidence was not reported in the seven observational studies. Prostate cancer was the only cancer type found to be increased after folic acid supplementation (meta-analyses of six RCTs). Prospective studies of cancer development in populations where food is fortified with folic acid could indicate whether fortification similar to supplementation moderately increases prostate cancer risk.

The soluble biomarker calprotectin (an S100 protein) is associated to ultrasonographic synovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab.

INTRODUCTION: Calprotectin (MRP8/MRP14, S100A8/A9) is associated with disease activity in patients with rheumatoid arthritis (RA). Ultrasonography (US) is a reliable method for evaluation of synovitis (B-mode (BM) and power Doppler (PD)). The present objectives were to explore in RA patients the associations between calprotectin and a comprehensive US examination, as well as the responsiveness of calprotectin compared to other inflammatory markers during anti-TNF treatment. METHODS: A total of 20 RA patients starting treatment with adalimumab were examined longitudinally by US (BM and PD (semi-quantitative scores 0 to 3) of 78 joints, 36 tendons/tendon groups and 2 bursae) and clinically at baseline and after 1, 3, 6 and 12 months. Associations between the US sum scores and the inflammatory markers calprotectin, serum amyloid A (SAA), CRP and ESR were explored by correlation and linear regression analyses, and the response to treatment was assessed by Standardized Response Mean (SRM). RESULTS: The inflammatory markers, clinical examinations and US sum scores improved during treatment (P < 0.001). Of the inflammatory markers, calprotectin had the highest correlation coefficients with the total BM and PD sum scores (median (range) 0.59 (0.37 to 0.76) for BM and 0.56 (0.38 to 0.72) for PD). Even higher correlations were found between calprotectin and sum US scores of reduced number of joint counts. Calprotectin made a considerable contribution to total US sum scores in the linear regression analyses (P = 0.001 to 0.031) and among the inflammatory markers, calprotectin had the highest SRM (0.84 at one month). CONCLUSIONS: Calprotectin was associated with the sum scores from a comprehensive US assessment and was responsive to change during anti-TNF treatment. Thus, examination of this leukocyte protein could be of additional value in the assessment of RA patients on biologic treatment.

[Treatment of amyloidosis]. / Behandling av amyloidose.

BACKGROUND: Treatment of amyloidosis is a substantial challenge. Various types of amyloidosis are associated with a broad spectrum of organ manifestations and considerable morbidity and mortality. MATERIAL AND METHODS: The present paper is based on a review of international literature, retrieved through a PubMed search on amyloidosis, and the author's clinical experience. RESULTS AND INTERPRETATION: Current treatment of amyloidosis is first and foremost aimed at reducing the level of amyloid precursor proteins; e.g. immunosuppression in AA amyloidosis, chemotherapy in AL amyloidosis and supportive treatment of diminished or lost organ function. Aggressive immunomodulating treatment increases survival in AA amyloidosis associated with rheumatic disease, and high-dose melphalan with autologous stem-cell transplantation (HMAS) has in selected studies shown increased survival in AL amyloidosis. More recent knowledge on mechanisms of amyloid formation has given rise to novel therapeutic targets that may be useful for all amyloidoses. Examples of this are immunotherapy and inhibition of the interaction of extrafibrillary components, which have shown benefit in animal models for AA, AL and Abeta amyloidosis as well as in the first human studies. More studies are needed to define their place in treatment of amyloidosis.

Articular, monoclonal gamma3 heavy-chain deposition disease: characterization of a partially deleted heavy-chain gene and its protein product synthesized in vivo and in vitro.

OBJECTIVE: A patient presented with heavy-chain deposition disease (HCDD), exhibiting severe erosive polyarthropathy caused by synovial deposits of abnormal monoclonal, heavily deleted free gamma3 heavy chains lacking the V(H) and C(H)1 domains. The absence of V(H) was surprising, since it is considered important for pathogenic tissue deposition. This study was undertaken to analyze the genetic structure of the heavy chain, the protein product synthesized in vitro, and that deposited in the synovium in comparison with the serum and urinary proteins. METHODS: Hybridomas were made by fusion of blood and bone marrow mononuclear cells with mouse myeloma cells. Cloned B cell hybridomas secreting gamma3 were selected and analyzed by polymerase chain reaction. Purified hybridoma Ig was sequenced by Edman degradation. Antiserum raised to a peptide corresponding to residues 2-15 of the truncated V(H) was used in Western blots of synovial tissue. RESULTS: The hybridomas secreted free gamma3 chains consisting of a V(H)4 gene truncated 21 nucleotides into the first complementarity-determining region and then reading straight into the hinge region. The amino acid sequence confirmed the presence of residues 1-32 of the V(H)4 gene. Immunoblotting of synovial tissue showed the presence of Ig with truncated V(H). CONCLUSION: The gamma3 heavy chain had a deletion of V(H) from codon 33 and of the entire C(H)1. In vivo, the 32 V(H) amino acids were proteolytically degraded. In the joint, however, the 32 residues of V(H) remained intact, consistent with a pathogenic role of V(H) for tissue deposition. To our knowledge, this is the first reported case of gammaHCDD causing an erosive, polyarticular arthropathy as the dominating clinical feature.