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Discover the most talked about and latest scientific content & concepts.

Journal: Annals of medicine

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The prevalence of monoclonal gammopathy of undetermined significance (MGUS) is generally estimated at 3.4% in the general population over 50 years, and its incidence increases with age. MGUS represents a preneoplastic entity that can transform into multiple myeloma or other lymphoproliferative disorders. The risk of malignant transformation is estimated at 1% per year and persists over time. Predictors of malignant transformation have been identified such as the heavy chain isotype, The level of monoclonal proteins, increasing levels of the monoclonal component during the first years off follow-up, the percentage of bone marrow plasmocytosis, the dosage of serum free light chains, the presence of immunophenotypically abnormal plasma cells, aneuploidy, and the presence of circulating plasma cells. Prognostic scores that combine certain of these factors have been proposed and allow the identification of high-risk patients. Their use could assist in tailoring the care for each patient, based on his/her risk profile.

Concepts: Multiple myeloma, Cancer, Bone marrow, Hematology, Monoclonal gammopathy of undetermined significance, Protein electrophoresis, Plasmacytoma, Paraprotein

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Tocilizumab is a highly effective therapeutic agent for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis. Furthermore, a large amount of case study data reveals that tocilizumab can be an effective therapy for not only rheumatoid arthritis but also for other mostly rare inflammatory rheumatic diseases. By blocking the interleukin-6 pathway tocilizumab can be a useful therapeutic alternative when conventional treatment fails. It is successful in treating diseases such as the adult-onset Still’s disease, amyloidosis, giant cell arteritis, multiple myeloma, polymyalgia rheumatica, relapsing polychondritis, remitting seronegative symmetrical synovitis with pitting edema-syndrome, systemic lupus erythematosus, systemic sclerosis, and Takayasu arteritis. Studies underway are now recruiting patients to acquire further data on treating patients with non-rheumatic arthritis, inflammatory diseases. This review focuses on tocilizumab as a promising agent for treating rare and orphan diseases in rheumatology for which no satisfactory treatment is yet available.

Concepts: Osteoporosis, Rheumatoid arthritis, Rheumatology, Systemic lupus erythematosus, Lupus erythematosus, Autoimmune diseases, Arthritis, Connective tissue diseases

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Abstract Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease with a lifetime risk in the UK population of almost 5%. An association between PD and Gaucher disease (GD) derived from the observation that GD patients and their heterozygous carrier relatives were at increased risk of PD. GD is an autosomal recessive lysosomal storage disorder caused by homozygous mutations in the gene encoding glucocerebrosidase (GBA). Approximately 5%-10% of PD patients have GBA mutations, making these mutations numerically the most important genetic predisposing risk factor for the development of PD identified to date. GBA mutations result in a phenotype that is virtually indistinguishable clinically, pharmacologically, and pathologically from sporadic PD, except GBA mutations result in a slightly earlier age of onset and more frequent cognitive impairment among PD patients. The mechanisms by which GBA mutations result in PD are not yet understood. Both reduced glucocerebrosidase enzyme (GCase) activity with lysosomal dysfunction, and unfolded protein response (UPR) with endoplasmic reticulum-associated degradation (ERAD) and stress are considered contributory.

Concepts: Lysosomal storage disease, Neurology, Neurodegenerative disorders, Parkinson's disease, Zygosity, Gaucher's disease, Glucocerebrosidase, Imiglucerase

25

Potatoes (Solanum tuberosum) are an important food crop worldwide and contribute key nutrients to the diet, including vitamin C, potassium, and dietary fiber. Potatoes and potato components have been shown to have favorable impacts on several measures of cardiometabolic health in animals and humans, including lowering blood pressure, improving lipid profiles, and decreasing markers of inflammation. A range of glycemic index (GI) values have been reported for potatoes, and data are sparse regarding the impact of potato consumption on the postprandial glycemic response, especially when potatoes are consumed with other foods. There is a lack of clinical trial data regarding the impact of potatoes on weight management. A small number of human cohort studies have reported beneficial associations between potato consumption as part of a healthy lifestyle and cardiometabolic health. Another small number of human population studies have included potatoes as part of a dietary pattern with other calorie-dense foods and have not reported cardiometabolic benefits. The epidemiological literature should be interpreted with caution due to lack of consistency in both defining dietary patterns that include potatoes and in control for potential confounding variables. Controlled clinical trials are needed to define the impact of potatoes on cardiometabolic health.

Concepts: Experimental design, Epidemiology, Clinical trial, Human, Nutrition, Carbohydrate, Glycemic index, Potato

24

Randomised controlled trials (RCTs) are commonly viewed as the best research method to inform public health and social policy. Usually they are thought of as providing the most rigorous evidence of a treatment’s effectiveness without strong assumptions, biases and limitations.

Concepts: Health care, Scientific method, Epidemiology, Clinical trial, Critical thinking, Randomized controlled trial

21

We aimed to evaluate the joint impact of cardiorespiratory fitness (CRF) and frequency of sauna bathing (FSB) on the risk of cardiovascular and all-cause mortality.

Concepts: Cohort study, Actuarial science, Cardiorespiratory fitness

18

Background: Hyperglycemia has emerged as an important risk factor for death in coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the association between blood glucose (BG) levels and in-hospital mortality in non-critically patients hospitalized with COVID-19.Methods:This is a retrospective multi-center study involving patients hospitalized in Spain. Patients were categorized into three groups according to admission BG levels: <140 mg/dl, 140-180 mg/dl, and >180 mg/dl. The primary endpoint wasall-cause in-hospital mortality.Results:Of the 11,312 patients, only 2,128 (18.9%) had diabetes, and2,289 (20.4%) diedduring hospitalization. The in-hospital mortality rates were 15.7% (<140 mg/dl), 33.7% (140-180 mg), and 41.1% (>180 mg/dl), p < 0.001. The cumulative probability of mortality was significantly higher in patients with hyperglycemia compared to patients with normoglycemia(log rank, p < 0.001), independently of pre-existingdiabetes.Hyperglycemia (after adjusting for age, diabetes, hypertension, and other confounding factors) was an independent risk factor of mortality (BG >180 mg/dl: HR 1.50; 95%CI: 1.31-1.73) (BG 140-180 mg/dl: HR 1.48; 95%CI: 1.29-1.70).Hyperglycemia was also associated with requirementformechanical ventilation, ICU admission,and mortality.Conclusion: Admission hyperglycemiais a strong predictor of all-cause mortality in non-critically hospitalized COVID-19 patients regardless ofprior history of diabetes. Key Messages:Admission Hyperglycemia is a stronger and independent risk factor for mortality in COVID-19.Screening for hyperglycemia, in patients without diabetes, and early treatment of hyperglycemia shouldbe mandatory in the management of patients hospitalized with COVID-19.Admission hyperglycemia should not be overlooked in all patients regardless prior history of diabetes.

17

FebriDx is a 10-minute disposable point-of-care test designed to identify clinically significant systemic host immune responses and aid in the differentiation of bacterial and viral respiratory infection by simultaneously detecting C-reactive protein (CRP) and myxovirus resistance protein A (MxA) from a fingerstick blood sample. FebriDx diagnostic accuracy was evaluated in the emergency room and urgent care setting.

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Purpose: We aimed to determine whether handgrip strength (HGS)improves type 2 diabetes (T2D) risk prediction beyond conventional risk factors.Design: Handgrip strengthwas assessedat baseline in 776individuals aged 60-72 years without a history of T2D in a prospective cohort. Handgrip strength was normalised to account for the effect of body weight.Hazard ratios (HRs) (95% confidence intervals [CI]) and measures of risk discrimination for T2Dand reclassification [net reclassification improvement (NRI), integrated discrimination index (IDI)] were assessed.Results: During 18.1 years median follow-up, 59 T2D events were recorded.The HR (95% CI)for T2Dadjusted for conventional risk factors was 0.49 (0.31-0.80) per 1 standard deviationhigher normalized HGSand was 0.54 (0.31-0.95) and 0.53 (0.29-0.97) on adjustment for risk factors in the DESIR and KORA S4/F4 prediction models, respectively.Adding normalized HGS to these risk scores was associated with improved risk prediction as measured by differences in -2 log likelihood, NRI and IDI.Sex-specific HRs and risk prediction findings using sensitive measures suggested the overallresultswere driven by thosein women.Conclusion: Adding measurements of HGS to conventional risk factors might improve T2D risk assessment, especially in women. Further evaluation is needed in larger studies. KEY MESSAGESHandgrip strength (HGS) is independently associated with reduced risk of type 2 diabetes (T2D), but its utility in classifying or predicting T2D risk has not been explored.In this prospective cohort study of older Caucasian men and women, adding measurements of HGS to conventional risk factors improved T2D risk assessment, especially in women.Assessment of HGS is simple and inexpensive and could prove a valuable clinical tool in the early identification of people at high risk of future T2D.

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Background. Inflammation may play an important role in type 2 diabetes. It has been proposed that dietary strategies can modulate inflammatory activity. Methods. We investigated the effects of diet on inflammation in type 2 diabetes by comparing a traditional low-fat diet (LFD) with a low-carbohydrate diet (LCD). Patients with type 2 diabetes were randomized to follow either LFD aiming for 55-60 energy per cent (E%) from carbohydrates (n = 30) or LCD aiming for 20 E% from carbohydrates (n = 29). Plasma was collected at baseline and after 6 months. C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra), IL-6, tumour necrosis factor receptor (TNFR) 1 and TNFR2 were determined. Results. Both LFD and LCD led to similar reductions in body weight, while beneficial effects on glycaemic control were observed in the LCD group only. After 6 months, the levels of IL-1Ra and IL-6 were significantly lower in the LCD group than in the LFD group, 978 (664-1385) versus 1216 (974-1822) pg/mL and 2.15 (1.65-4.27) versus 3.39 (2.25-4.79) pg/mL, both P < 0.05. Conclusions. To conclude, advice to follow LCD or LFD had similar effects on weight reduction while effects on inflammation differed. Only LCD was found significantly to improve the subclinical inflammatory state in type 2 diabetes.

Concepts: Inflammation, Protein, Nutrition, Obesity, Receptor, Carbohydrate, C-reactive protein, Low-carbohydrate diet