The role of disease severity in influencing body mass index in people with haemophilia: a single‐institutional cross‐sectional study

The aim of this study was to evaluate the effect of haemophilia disease severity and potential intermediaries on body mass index (BMI) in patients with haemophilia. A secondary analysis of a cross‐sectional study of 88 adults with haemophilia was undertaken. On bivariate analysis, persons with severe haemophilia had 9.8% lower BMI (95% CI ?17.1, ?3.0) than persons with non‐severe haemophilia. The effect of haemophilia severity on BMI varied significantly by human immunodeficiency virus (HIV) status. Among HIV‐positive subjects, haemophilia severity was not associated with BMI (+5.0%, 95% CI ?22.4, 41.9). Among HIV‐negative subjects, severe haemophilia was associated with 15.1% lower BMI (95% CI, ?23.6, ?5.7). Older (>41 years) HIV‐negative subjects with severe haemophilia had a BMI that was 24.8% lower (95% CI ?39.1, ?7.0) than those with non‐severe haemophilia. No statistically significant association was detected between BMI and severe vs. non‐severe haemophilia for younger HIV‐negative subjects. Although joint disease, as measured by the World Federation of Hemophilia (WFH) joint score, did not influence the association between haemophilia disease severity and BMI, adjustment for the atrophy component of the WFH score reduced the association between haemophilia severity and BMI by 39.1–69.9%. This suggested that muscle atrophy mediated at least part of the relationship between haemophilia severity and BMI. Haemophilia disease severity is associated with BMI and appears to be mediated by muscle atrophy of surrounding joints. This association appears to be modified by HIV status and possibly age.     

Bone density in haemophilia: a single institutional cross‐sectional study

Haemophilia has been associated with low bone mineral density (BMD). However, prior clinical studies of this population have neither clearly elucidated risk factors for development of low BMD nor identified who may warrant screening for osteoporosis. The aim of the study was to evaluate the relationship between BMD and haemophilic arthropathy and other demographic and clinical variables. We undertook a cross‐sectional study of BMD in adult men with haemophilia. Measures of predictor variables were collected by radiographic studies, physical examination, patient questionnaires and review of medical records. Among 88 enrolled subjects, the median age was 41 years (IQR: 20); median femoral neck BMD (n = 87) was 0.90 g cm^?2 (IQR: 0.24); and median radiographic joint score was 7.5 (IQR: 18). Among subjects <50 years (n = 62), after controlling for BMI, alcohol, HIV and White race, BMD decreased as radiographic joint score increased (est. β = ?0.006 mg cm^?2; 95% CI ?0.009, ?0.003; partial R² = 0.23). Among subjects ≥50 years (n = 26), 38% had osteoporosis (T score less than or equal to ?2.5) and there was no association between BMD and arthropathy. Risk factors for low BMD in men with haemophilia <50 years include haemophilic arthropathy, low or normal BMI and HIV. Men with haemophilia over age 50 years should have routine screening for detection of osteoporosis.     

On instabilities of deep learning in image reconstruction and the potential costs of AI

Deep learning, due to its unprecedented success in tasks such as image classification, has emerged as a new tool in image reconstruction with potential to change the field. In this paper, we demonstrate a crucial phenomenon: Deep learning typically yields unstable methods for image reconstruction. The instabilities usually occur in several forms: 1) Certain tiny, almost undetectable perturbations, both in the image and sampling domain, may result in severe artefacts in the reconstruction; 2) a small structural change, for example, a tumor, may not be captured in the reconstructed image; and 3) (a counterintuitive type of instability) more samples may yield poorer performance. Our stability test with algorithms and easy-to-use software detects the instability phenomena. The test is aimed at researchers, to test their networks for instabilities, and for government agencies, such as the Food and Drug Administration (FDA), to secure safe use of deep learning methods.     

Salmonella infection-associated acute rhabdomyolysis. Some pathogenic considerations

Rhabdomyolysis is a syndrome characterized by extended myolysis, elevation of serum aminotransferases and creatine kinase, and myoglobinuria. It is a rare but well-established complication of a spectrum of infectious diseases. Salmonella infections have been connected with this syndrome as well. We present here the case of a 58-year-old female affected by Charcot-Marie-Tooth (CMT) disease, a type of hereditary neuropathy, who presented with acute renal failure and rhabdomyolysis syndrome in the course of Salmonella infantis gastroenteritis. We formed some considerations on the pathogenesis of rhabdomyolysis in this specific setting based on certain experimental works on the Salmonella pathogenic cycle. We concluded that the calcium-dependent mechanism coupled with a predisposing factor might be of major significance in the development of this complication.     

Physical activity and functional abilities in adult males with haemophilia: a cross‐sectional survey from a single US haemophilia treatment centre

Physical activity and functional ability are important determinants of quality of life and these metrics are affected by both haemophilia and ageing. Outside haemophilic arthropathy, risk factors leading to reduced physical activity and function in people with haemophilia (PWH) are under‐explored. The purpose of this analysis was to determine risk factors for reduced physical activity and functional limitations in PWH. A secondary analysis was conducted on data indexing physical activity and functioning of 88 PWH using data originally collected as part of a cross‐sectional study at a single large haemophilia treatment centre. The Framingham Physical Activities Index (PAI), the Hemophilia Activities List (HAL) and the Timed Up‐and‐Go Test (TUG) were the outcome measures. The World Federation of Haemophilia (WFH) orthopaedic joint score was used as a measure of arthropathy. Multiple linear regression analysis was used to assess the relationship between the outcome measures and covariates. Worsening WFH joint score was independently associated with all three outcome measures (P < 0.05). Increasing age was associated with reduced PAI and increased TUG time (P < 0.05). The HAL summary score was decreased in patients with chronic liver disease (P = 0.006). The adjusted R² for each model was ≤0.35. This study provides evidence for the relationship between arthropathy and reduced physical functioning/activity, but also highlights that much of the variation in physical functioning/activity is not explained by haemophilia‐related characteristics.     

Respiratory function and immunological status in workers employed in a latex glove manufacturing plant

A study was performed in 17 female workers employed in a latex glove manufacturing plant. The mean age of these workers was 42 years and the mean duration of their employment was 19 years. The employees were primarily nonsmokers or light smokers. The presence of chronic respiratory symptoms and acute work-related symptoms was recorded for these workers. Ventilatory capacity was measured during the morning work shift by recording maximum expiratory flow-volume curves from which forced vital capacity (FVC), 1-second forced expiratory volume (FEV₁) and maximum expiratory flow at 50%, and the last 25% of the vital capacity (FEF₅₀, FEF₇₅) were measured. A control group of 17 nonexposed women workers was also studied. The prevalence of chronic respiratory symptoms was greater among latex workers than among control confectionry packer workers, varying from 5.9% (vs. 0% in controls) for occupational asthma to 58.8% (vs. 0% in controls) for dyspnea grades 3 or 4. There was also a high prevalence of acute work-related symptoms in this industry, in particular, eye irritation (76.5%), dryness of the nose (70.6%), throat burning (70.6%), dryness of the throat (64.7%), and cough (58.8%). Among exposed workers, measured ventilatory capacity data were significantly lower than among controls, particularly FEF₇₅ (75.1% ± 10.5%). One of the 17 studied workers (5.9%) had a positive skin reaction to latex and had symptoms compatible with occupational asthma. Our data suggest that in addition to occupational asthma, the manufacture of latex gloves is associated with frequent, nonspecific respiratory findings. Am. J. Ind. Med. 33:175–181, 1998. © 1998 Wiley-Liss, Inc.     

Association of Nephrolithiasis and Gene for Glucose Transporter Type 9 (SLC2A9): Study of 145 Patients

Aim

To investigate the association of nephrolithiasis and solute carrier family 2, facilitated glucose transporter, member 9 (SLC2A9), also known as glucose transporter type 9, Glut9.

Methods

A total of 145 participants were recruited in the period April-October 2008 from the Department of Mineral Research of the Medical School Osijek, Osijek, Croatia; 58 (40%) had confirmed nephrolithiasis and 87 (60%) were asymptomatic. Four single nucleotide polymorphisms (SNP) from the SLC2A9 gene were genotyped in both groups (rs733175, rs6449213, rs1014290, and rs737267).

Results

There was a weak but significant association of all 4 SNPs and nephrolithiasis (P = 0.029 for rs733175; P = 0.006 for rs6449213; P = 0.020 for rs1014290, and P = 0.011 for rs737267). Logistic regression in an age- and sex-adjusted model suggested that genotype C/T for rs6449213 had odds ratio for nephrolithiasis of 2.89 (95% confidence interval 1.13-7.40). This SNP explained a total of 4.4% of nephrolithiasis variance.

Conclusion

Development of nephrolithiasis may be associated with SLC2A9 gene. Further studies are needed to clarify the role of SLC2A9 gene as a link between uric acid and nephrolithiasis.Renal stone formation (nephrolithiasis) is a disease characterized by the existence of solid deposits in the upper parts of the urinary tract (1). It is estimated to affect between 3%-9% of the population, with large differences between various populations (2,3). There is a number of causes that may lead to the renal stones formation, including diet and obesity status, some drugs, other diseases, climate changes, metabolic disorders, and genetic factors (2,4,5). The complexity of this disease caused researchers to consider nephrolithiasis as one feature of a broader systemic disease, rather than a local disease restricted to a single organic system (6). This is especially interesting in relation to gout and metabolic syndrome, which are both systemic disorders in close relation to nephrolithiasis (6-8). Even the cohort studies have confirmed the association of gout and kidney stones, suggesting that the history of gout increases the risk for kidney stones (9). Another study showed that, in the age-adjusted model, gout had an odds ratio of 1.97 for previous kidney stones (95% confidence interval [CI], 1.37-2.83) and that even after adjustment for sex, race, body mass index, and presence of hypertension the odds ratio remained significant (10).Genetic contribution to renal stones formation has been identified long time ago (2). In line with these suggestions, heritability of some of the traits associated with nephrolithiasis has been shown to be as high as 95% (11). Heritability of the urinary stones was reported to be lower (56%) (12), but still sufficiently high to be considered a substantial genetic proportion of variance and suggesting that it may be under genetic control. So far, a number of studies have established a link between predominantly oxalate kidney stones and several genes, including vitamin-D receptor gene (VDR) and calcitonin receptor (CTR) gene (13), heparan sulfate (HSPG2) gene (14), or fibronectin gene (FN1) (14).The quantitative trait associated with nephrolithiasis is the serum uric acid concentration, which is under strong genetic control by the gene for glucose transporter type 9 (SLC2A9 or Glut 9) (15). The gene was initially described in an isolated island community (16,17), where genetic properties of the population are expected to act in favor of facilitated gene mapping efforts (18). Subsequent meta-analysis of 14 populations confirmed the association of this gene with serum uric acid concentrations (19). This led to a number of clinical studies that have confirmed its involvement in the uric acid metabolism, including urate handling in the kidney and uptake in the liver (20,21). Based on the previous suggestions that gout and nephrolithiasis may share a common pathway (15), it might be interesting to see if SLC2A9 could explain the commonalities in patients with any of the following conditions. Therefore, the aim of this study was to investigate the association of nephrolithiasis and genetic variants of the SLC2A9.