Multidisciplinary Management of Mastocytosis : Nordic Expert Group Consensus

Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.Peer reviewe

Diabetic osteopathy and the IGF system in the Goto-Kakizaki rat

Objective:Diabetes mellitus is associated with an increased risk of osteopenia, fracture and Charcot arthropathy. Abnormalities of the IGF system commonly observed in diabetes may underlie this diabetic osteopathy as IGF-I and its binding proteins (IGFBPs) have been shown to affect osteoblast and osteoclast activity. Design: In type-2 diabetic and control rats we analyzed IGF-I and IGFBP-1 and -4 levels in serum, and notably, also the IGF-I levels in cortical bone, ankles and vertebrae by immunoassays. Osteopathy was assessed by radiography and dual energy X-ray absorptiometry. Results: In the diabetic rats IGF-I was significantly reduced in serum and diaphyseal bone while IGFBP-1 and IGFBP-4 were increased in serum. The periosteal and endosteal diameters were increased in the diaphysis of humerus and tibia (changes similar to those in elderly humans) while bone mineral density was reduced in long bone metaphyses and vertebrae. Conclusions: Our study demonstrates both systemic and local disturbances of the IGF-system in rats with type-2 diabetes, consistent with the observed enhanced endosteal erosion in long bone diaphyses, and osteopenia in metaphyses and vertebrae. Whether similar IGF-system changes contribute to osteopathy in Patients with diabetes and if treatment of diabetes can reverse the osteopathy has yet to be explored

Impact of radiotherapy on bone health in women with rectal cancer- A prospective cohort study

Introduction: Pelvic radiotherapy (RT) increases the risk of pelvic insufficiency fractures. The aim was to investigate if RT is associated with changes in serum bone biomarkers in women with rectal cancer, and to examine the incidence of radiation-induced bone injuries and the association with bone biomarkers.Material and methods: Women diagnosed with rectal cancer stage I-III, planned for abdominal surgery +/- preoperative (chemo) RT, were prospectively included and followed one year. Serum bone biomarkers comprised sclerostin (regulatory of bone formation), CTX (resorption), BALP and PINP (for-mation). A subgroup was investigated with annual pelvic magnetic resonance imaging (MRI). The as-sociation between RT and bone biomarkers was explored in regression models.Results: Of 134 included women, 104 had surgery with preoperative RT. The formation markers BALP and PINP increased from baseline to one year in the RT-exposed group (p &amp;lt; 0.001, longitudinal comparison). In the adjusted regression analysis, the mean increase in PINP was higher in the RT-exposed than the unexposed group (17.6 (3.6-31.5) mg/L, p = 0.013). Sclerostin and CTX did not change within groups nor differed between groups. Radiation-induced injuries were detected in 16 (42%) of 38 women with available MRI. At one year, BALP was higher among women with than without bone injuries (p = 0.018, cross-sectional comparison).Conclusions: Preoperative RT was associated with an increase in the formation marker PINP, which could represent bone recovery following RT-induced injuries, commonly observed in participants evaluated with MRI. These findings should be further explored in larger prospective studies on bone health in rectal cancer patients.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Funding Agencies|Swedish Cancer Society; Stockholm Cancer Society; Bengt Ihre Research Fellowship; Bengt Ihre Foundation; Stockholm County Council; Karolinska Institutet; Region Ostergotland</p

Type B insulin resistance syndrome in a patient with type 1 diabetes

Type B insulin resistance syndrome (TBIRS) is a very rare autoimmune disorder with polyclonal autoantibodies against the insulin receptor, resulting in severe and refractory hyperglycemia. Described here is a patient who within a few months after the onset of autoimmune type 1 diabetes increased her insulin requirements more than 20-fold; despite this she had considerable difficulty maintaining a plasma glucose value of &lt;40-60 mmol/L (720-1100 mg/dL). On suspicion of TBIRS, the patient was started on tapering dose of glucocorticoids to overcome the autoimmune insulin receptor blockade, resulting in an immediate and pronounced effect. Within days, insulin requirements decreased by 80-90% and plasma glucose stabilized around 7-8 mmol/L (126-144 mg/dL). The presence of antibodies to the insulin receptor was detected by immunoprecipitation and binding assays. After a 4-month remission on low maintenance dose prednisolone, the patient relapsed, which required repeated plasmaphereses and immune column treatments with temporarily remarkable effect. Mixed and transient results were seen with rituximab, mycophenolic acid and bortezomib, but the glycemic status remained suboptimal. Lack of compliance and recurrent infections may have contributed to this

Additive effects of nutritional supplementation, together with bisphosphonates, on bone mineral density after hip fracture : a 12-month randomized controlled study

Background: After a hip fracture, a catabolic state develops, with increased bone loss during the first year. The aim of this study was to evaluate the effects of postoperative treatment with calcium, vitamin D, and bisphosphonates (alone or together) with nutritional supplementation on total hip and total body bone mineral density (BMD). Methods: Seventy-nine patients (56 women), with a mean age of 79 years (range, 61-96 years) and with a recent hip fracture, who were ambulatory before fracture and without severe cognitive impairment, were included. Patients were randomized to treatment with bisphosphonates (risedronate 35 mg weekly) for 12 months (B; n=28), treatment with bisphosphonates along with nutritional supplementation (40 g protein, 600 kcal daily) for the first 6 months (BN; n=26), or to controls (C; n=25). All participants received calcium (1,000 mg) and vitamin D3 (800 IU) daily. Total hip and total body BMD were assessed with dual-energy X-ray absorptiometry at baseline, 6, and 12 months. Marker of bone resorption C-terminal telopeptide of collagen I and 25-hydroxy vitamin D were analyzed in serum. Results: Analysis of complete cases (70/79 at 6 months and 67/79 at 12 months) showed an increase in total hip BMD of 0.7% in the BN group, whereas the B and C groups lost 1.1% and 2.4% of BMD, respectively, between baseline and 6 months (P=0.071, between groups). There was no change in total body BMD between baseline and 12 months in the BN group, whereas the B group and C group both lost BMD, with C losing more than B (P=0.009). Intention-to-treat analysis was in concordance with the complete cases analyses. Conclusion: Protein-and energy-rich supplementation in addition to calcium, vitamin D, and bisphosphonate therapy had additive effects on total body BMD and total hip BMD among elderly hip fracture patients

Gender differences and cognitive aspects on functional outcome after hip fracture-a 2 years' follow-up of 2,134 patients

Objective: we analysed outcome after hip fracture with respect to gender and cognitive function. Design: population-based, prospective cohort study. Setting: four university hospitals in Stockholm, Sweden. Subjects: a total of 2,134 consecutive patients admitted with hip fracture during 2003. Methods: gender differences in residence, walking ability and activity of daily living (ADL) were analysed at baseline, after 4 and 24 months in patients with and without intact cognitive function. Results: women were older, more often living alone and had poorer walking ability (P < 0.001). Cognitive dysfunction was equally common by gender. Women were more often treated with a prosthesis (P < 0.001) and sent to rehabilitation (P < 0.001). In the cognitive dysfunction group, men had more co-morbidity (P < 0.001) and total loss of walking ability (P = 0.03), but more often resided in own homes (P = 0.03). There was no gender difference in ADL. Conclusion: men had a higher risk for loss of walking ability and death only in patients with cognitive dysfunction. Cognitive function was the most important factor for returning to own home and regain pre-fracture function

Characterization of the swelling potential of expansive clays using centrifuge technology

textThe characterization of the swell potential of expansive clay is complicated by the fact that traditional swell testing methods require an excessive amount of time for specimens to swell to their maximum heights. As a result, the practicing engineer has typically referred to correlations between swell potential and index properties rather than directly measuring swelling in a laboratory experiment. The purpose of this study is to evaluate an alternate testing method using a geotechnical centrifuge in an attempt to decrease the time required to evaluate the swell potential of expansive clays so that expermientally obtained swelling properties may be obtained within a reasonable time period. This study includes an experimental program involving a series of tests in which compacted clay specimens are flown in a cetrifuge and their heights are monitored as water infiltrates into them.Civil, Architectural, and Environmental Engineerin

Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial.

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p &lt; 0.01) and QCT (5.7%, p &lt; 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p &lt; 0.0001), total hip (10.8%, p &lt; 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p &lt; 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength