Quantitative ultrasound does not identify patients with an inflammatory disease at risk of vertebral deformities

<p>Abstract</p> <p>Background</p> <p>Previous studies from our group have shown that a high prevalence of vertebral deformities suggestive of fracture can be found in patients with an inflammatory disease, despite a near normal bone mineral density (BMD). As quantitative ultrasound (QUS) of the heel can be used for refined assessment of bone strength, we evaluated whether QUS can be used to identify subjects with an inflammatory disease with an increased chance of having a vertebral fracture.</p> <p>Methods</p> <p>246 patients (mean age: 44 ± 12.4 years) with an inflammatory disease (sarcoidosis or inflammatory bowel disease (IBD)) were studied. QUS of the heel and BMD of the hip (by dual X-ray absorptiometry (DXA)) were measured. Furthermore lateral single energy densitometry of the spine for assessment of vertebral deformities was done. Logistic regression analysis was performed to assess the strength of association between the prevalence of a vertebral deformity and BMD and QUS parameters, adjusted for gender and age.</p> <p>Results</p> <p>Vertebral deformities (ratio of <0.80) were found in 72 vertebrae of 54 subjects (22%). In contrast to the QUS parameters BUA (broadband ultrasound attenuation) and SOS (speed of sound), T-score of QUS and T-scores of the femoral neck and trochanter (DXA) were lower in the group of patients with vertebral deformities. Logistic regression analysis showed that the vertebral deformity risk increases by about 60 to 90% per 1 SD reduction of BMD (T-score) determined with DXA but not with QUS.</p> <p>Conclusion</p> <p>Our findings imply that QUS measurements of the calcaneus in patients with an inflammatory condition, such as sarcoidosis and IBD, are likely of limited value to identify patients with a vertebral fracture.</p

Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants inLARS1

Purpose: Biallelic variants in LARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Methods: Individuals with biallelic variants in LARS1 were included through an international, multicenter collaboration including novel and previously published patients. Clinical variables were analyzed and functional studies were performed in patient-derived fibroblasts. Results: Twenty-five individuals from 15 families were ascertained including 12 novel patients with eight previously unreported variants. The most prominent clinical findings are recurrent elevation of liver transaminases up to liver failure and encephalopathic episodes, both triggered by febrile illness. Magnetic resonance image (MRI) changes during an encephalopathic episode can be consistent with metabolic stroke. Furthermore, growth retardation, microcytic anemia, neurodevelopmental delay, muscular hypotonia, and infection-related seizures are prevalent. Aminoacylation activity is significantly decreased in all patient cells studied upon temperature elevation in vitro. Conclusion: ILFS1 is characterized by recurrent elevation of liver transaminases up to liver failure in conjunction with abnormalities of growth, blood, nervous system, and musculature. Encephalopathic episodes with seizures can occur independently from liver crises and may present with metabolic stroke

Eating at the right time of day: An underappreciated lifestyle therapy for hypertension?

Daily cycles of light and dark due to the rotation of the earth around its axis have dictated how life has evolved on Earth. Organisms have thus developed the ability to predict these 24-h cycles by developing an endogenous circadian clock, which is entrained to external cues. In mammals, circadian rhythms are controlled and generated by the central or master circadian clock located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus in the brain [1]. This master clock consists of multiple single-cell circadian oscillators that are synchronized to 24 h by environmental factors, primarily dark/light and also temperature and food. The retina perceives the dark/light cycle information and transmits this signal to the SCN via the retinohypothalamic tract. The SCN then transmits these inputs to peripheral oscillators located outside the SCN. Such peripheral oscillators exist in nearly all peripheral tissues such as liver, adipose, pancreas, muscle and blood. Therefore, circadian rhythms have been described for virtually all physiological and biochemical processes, including behavioural ones [2]

Eating at the right time of day: an underappreciated lifestyle therapy for hypertension?

Daily cycles of light and dark due to the rotation of the earth around its axis have dictated how life has evolved on Earth. Organisms have thus developed the ability to predict these 24-h cycles by developing an endogenous circadian clock, which is entrained to external cues. In mammals, circadian rhythms are controlled and generated by the central or master circadian clock located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus in the brain [1]. This master clock consists of multiple single-cell circadian oscillators that are synchronized to 24 h by environmental factors, primarily dark/light and also temperature and food. The retina perceives the dark/light cycle information and transmits this signal to the SCN via the retinohypothalamic tract. The SCN then transmits these inputs to peripheral oscillators located outside the SCN. Such peripheral oscillators exist in nearly all peripheral tissues such as liver, adipose, pancreas, muscle and blood. Therefore, circadian rhythms have been described for virtually all physiological and biochemical processes, including behavioural ones [2]

It is time to integrate conventional therapy by ozone therapy in type-2 diabetes patients

Editorial

Associations Between the Ankle-Brachial Index and Cardiovascular and All-Cause Mortality Are Similar in Individuals Without and With Type 2 Diabetes Nineteen-year follow-up of a population-based cohort study

OBJECTIVE: In the general population, a low ankle-brachial index (ABI) (<0.9) is strongly associated with (cardiovascular) mortality. However, the association between the ABI and mortality may be weaker in individuals with diabetes, as ankle pressures may be elevated by medial arterial calcification and arterial stiffening, which occur more frequently in diabetes. Therefore, the aim of this study was to compare the association between ABI and mortality in individuals without and with diabetes. RESEARCH DESIGN AND METHODS: We studied the associations between ABI and cardiovascular and all-cause mortality in 624 individuals from the Hoorn study, a population-based cohort of 50- to 75-year-old individuals (155 with diabetes and 469 without) followed for a median period of 17.2 years. Data were analyzed using Cox proportional hazards models. RESULTS: During the follow-up period, 289 of 624 (46.3%) participants died (97 of 155 with and 192 of 469 without diabetes and 52 of 65 with and 237 of 559 without ABI <0.9): 85 (29.4%) of CVD (30 of 155 with and 55 of 469 without diabetes and 20 of 65 with and 65 of 559 without ABI <0.9). A low ABI was strongly associated with cardiovascular mortality (relative risk 2.57 [95% CI 1.50–4.40]) and all-cause mortality (2.02 [1.47–2.76]), after adjustment for Framingham risk factors. The associations of the ABI with mortality did not differ between individuals without and with diabetes for cardiovascular (P(interaction) = 0.45) or all-cause (P(interaction) = 0.63) mortality. CONCLUSIONS: In the Hoorn Study, associations between ABI and cardiovascular and all-cause mortality were similar in individuals without and with diabetes. Future studies should investigate, in both individuals without and with diabetes, whether measurement of ABI can be used to guide treatment decisions

F-18 FDG PET/CT scanning in Charcot disease: a brief report

PURPOSE: because of the increasing prevalence of diabetes, complications of diabetes will also become more prevalent. The pathophysiology of Charcot neuro-osteoarthropathy (Charcot disease) as a complication of diabetes is still enigmatic. As a consequence, the optimal diagnostic, follow-up, and therapeutic strategies are unclear. To obtain more insight into the relation between bony abnormalities and the (concurrent) inflammatory response in acute Charcot disease, thereby creating more insight into the pathophysiology of this disease, we performed F-18 FDG PET/CT scanning. RESEARCH DESIGN AND METHODS: We performed F-18 FDG PET/CT and Tc-99m bone scintigraphy in 10 patients with Charcot disease. Bony abnormalities on CT-scan and areas of increased uptake on F-18 FDG PET and Tc-99m bone scintigraphy were assessed independently. Subsequently, fused PET/CT images were evaluated for number and location of PET lesions. RESULTS: nine patients had increased uptake of F-18 FDG, indicating inflammation, in 25 areas of soft tissue and/or bone without concurrent bony abnormalities on CT. CONCLUSIONS: presented F-18 FDG PET/CT data may indicate an inflammatory origin of Charcot disease, with secondary bone resorption, possibly due to decreased inhibitory neurogenic inflammatory responses as a result of small fiber neuropathy. If these findings can be confirmed in future studies, F-18 FDG PET/CT scanning may be added to the diagnostic arsenal in Charcot disease, and anti-inflammatory drugs may be added to the therapeutic arsenal

Glyoxalase-1 overexpression partially prevents diabetes-induced impaired arteriogenesis in a rat hindlimb ligation model

We hypothesize that diabetes-induced impaired collateral formation after a hindlimb ligation in rats is in part caused by intracellular glycation and that overexpression of glyoxalase-I (GLO-I), i.e. the major detoxifying enzyme for advanced-glycation-endproduct (AGE) precursors, can prevent this. Wild-type and GLO-I transgenic rats with or without diabetes (induced by 55 mg/kg streptozotocin) were subjected to ligation of the right femoral artery. Laser Doppler perfusion imaging showed a significantly decreased blood perfusion recovery after 6 days in the diabetic animals compared with control animals, without any effect of Glo1 overexpression. In vivo time-of-flight magnetic resonance angiography at 7-Tesla showed a significant decrease in the number and volume of collaterals in the wild-type diabetic animals compared with the control animals. Glo1 overexpression partially prevented this decrease in the diabetic animals. Diabetes-induced impairment of arteriogenic adaptation can be partially rescued by overexpressing of GLO-I, indicating a role of AGEs in diabetes-induced impaired collateral formation