Diabetic peripheral neuropathy in people with type 2 diabetes: too little too late

Diabetic peripheral neuropathy in people with type 2 diabetes is poorly managed because of its insidious onset, delayed diagnosis and more complex aetiology resulting from the contribution of not only hyperglycaemia, but also ageing, hyperlipidaemia, hypertension and obesity. Because there is no US Food and Drug Adminstration-approved disease-modifying therapy for diabetic peripheral neuropathy, the key to ameliorating it in type 2 diabetes has to be through earlier diagnosis and timely multi-factorial risk factor reduction. The management of painful diabetic peripheral neuropathy also requires a detailed appraisal of the choice of therapy, taking into account efficacy, patient wishes, comorbidities, side effect profile and potential for abuse.     

In‐hospital worsening heart failure

Acute worsening heart failure (WHF) is seen in a sizable portion of patients hospitalized for heart failure, and is increasingly being recognized as an entity that is associated with an adverse in‐hospital course. WHF is generally defined as worsening heart failure symptoms and signs requiring an intensification of therapy, and is reported to be seen in anywhere from 5% to 42% of heart failure admissions. It is difficult to ascertain the exact epidemiology of WHF due to varying definitions used in the literature. Studies indicate that WHF cannot be precisely predicted on the basis of baseline variables assessed at the time of admission. Recent data suggest that some experimental therapies may reduce the risk of development of WHF among hospitalized heart failure patients, and this is associated with a reduction in risk of subsequent post‐discharge cardiovascular mortality. In this respect, WHF holds promise as a endpoint for acute heart failure clinical trials to better elucidate the benefit of targeted novel therapies. Better understanding of the pathophysiology and a consensus on the definition of WHF will further improve our epidemiological and clinical understanding of this entity.     

Evaluation of Moisture Damage Potential in Hot Mix Asphalt Using Polymeric Aggregate Treatment

To enhance the moisture damage performance of hot mix asphalt (HMA), treating the aggregate surface with a suitable additive was a more convenient approach. In this research, two types of aggregate modifiers were used to study the effect of moisture damage on HMA. Three different aggregate sources were selected based on their abundance of use in HMA. To study the impact of these aggregate modifiers on moisture susceptibility of HMA, the indirect tensile strength test and indirect tensile modulus test were used as the performance tests. Moisture conditioning of specimens was carried out to simulate the effect of moisture on HMA. The prepared samples’ tensile strength ratio (TSR) and stiffness modulus (Sm) results indicated a decrease in the strength of the HMA after moisture conditioning. After treating the aggregate surface with additives, an improvement was seen in dry and wet strength and stiffness. Moreover, an increasing trend was observed for both additives. The correlation between TSR and strength loss reveals a strong correlation (R² = 0.7219). Also, the two additives indicate increased wettability of asphalt binder over aggregate, thus improving the adhesion between aggregate and asphalt binder.     

Tethered cord syndrome: overview of diagnosis and treatment

This article covers the basis of tethered cord syndrome as a stretch-induced spinal cord disorder, including pathophysiology, signs and symptoms, imaging diagnosis, indication for surgical treatment, and surgical procedures. Anomalies that cause mechanical spinal cord tethering are listed, and the surgical untethering technique for each anomaly is described.     

Vitamin D3 analog, EB1089, inhibits growth of subcutaneous xenografts of the human colon cancer cell line, LoVo, in a nude mouse model

PURPOSE: In this study, we investigated the effect of the vitamin D ₃ analog, EB1089, on the growth of subcutaneous xenografts of the human colon cancer cell line, LoVo, in a nude mouse model. METHODS: BALB/c Nu/Nu nude mice were inoculated subcutaneously with 10 ⁶ LoVo cells. EB1089 dissolved in isopropanol was administered intraperitoneally and orally on alternate days at doses of 0.1, 0.5, and 2.5 g/kg/day. Control animals received isopropanol alone. Tumor volumes estimated using the formula 0.5×length×(width). The tumor kinetic index was determined by immunohistochemical detection of proliferating cell nuclear antigen. RESULTS: Significant dose-dependent inhibition of tumor growth was seen. After 20 days of treatment with 0.1 g/kg/day EB1089, mean tumor volume in treated mice was 41 to 49 percent less than that in control animals (P <0.01). Significant inhibition of tumor growth was also seen with 0.5 g/kg/day EB1089 after 22 days of treatment (51 percent of control P <0.01). Treatment with 2.5 g/kg/day resulted in weight loss that required termination of this group; these mice were subsequently found to be hypercalcemic. The tumor kinetic index was significantly lower in tumors treated with 0.1 g/kg/day EB1089 compared with that for control tumors (8 vs.30 percent in controls). CONCLUSION: These findings suggest that the vitamin D ₃ analog, EB1089, is a potent antiproliferative agent for some human colon cancers.The human colonic adenocarcinoma cancer cell line, LoVo, was a gift from CRC Laboratories, Nottingham, United Kingdom.Read at the Royal Australasian College of Surgeons Annual Scientific Congress, Melbourne, Australia, June 5 to 10, 1996.     

Determinants of Diuretic Responsiveness and Associated Outcomes During Acute Heart Failure Hospitalization: An Analysis From the NHLBI Heart Failure Network Clinical Trials

Background

Poor response to loop diuretic therapy is a marker of risk during heart failure hospitalization. We sought to describe baseline determinants of diuretic response and to further explore the relationship between this response and clinical outcomes.

Effect of intravenous iron replacement on recurrent heart failure hospitalizations and cardiovascular mortality in patients with heart failure and iron deficiency: A Bayesian meta-analysis

Aims

Iron deficiency is common in patients with heart failure (HF) and reduced ejection fraction (HFrEF) and is associated with a poor prognosis. Whether intravenous iron replacement improves recurrent HF hospitalizations and cardiovascular mortality of these patients is uncertain although several trials were conducted. Moreover, none of the trials were powered to assess the effect of intravenous iron in clinically important subgroups. Therefore, we conducted a Bayesian analysis to derive precise estimates of the effect of intravenous iron replacement on recurrent HF hospitalizations and cardiovascular mortality in iron-deficient HFrEF patients using consistent subgroup definitions across trials.

Methods and results

Individual participant data were used from the FAIR-HF (n = 459), CONFIRM-HF (n = 304) and AFFIRM-AHF (n = 1108) trials. These data were re-analysed following as closely as possible the approach taken in the analyses of IRONMAN (n = 1137), for which study level data were used. Definitions of outcomes and subgroups from the FAIR-HF, CONFIRM-HF and AFFIRM-AHF were matched with those used in IRONMAN. The primary endpoint was recurrent HF hospitalizations and cardiovascular mortality. The analysis of recurrent events was based on rate ratios (RR) derived from the Lin-Wei-Yang-Ying model, and the data were pooled using Bayesian random-effects meta-analysis. Compared with placebo, intravenous iron significantly reduced the rates of recurrent HF hospitalizations and cardiovascular mortality (RR 0.73, 95% credible interval [CI] 0.48–0.99; between-trial heterogeneity tau = 0.16). The pooled treatment effects did not provide evidence for any differential effects for subgroups based on sex (ratio of rate ratios [RRR] 1.49 [95% CI 0.95–2.37], age <69.4 vs. ≥69.4 years) (RRR 0.68 [0.40–1.15]), ischaemic versus non-ischaemic aetiology of HF (RRR 0.73 [0.42–1.33]), transferrin saturation <20% vs. ≥20% (RRR 0.75 [0.40–1.34]), estimated glomerular filtration rate ≤60 versus >60 ml/min/1.73 m² (RRR 0.97 [0.56–1.68]), haemoglobin <11.8 versus ≥11.8 (RRR 0.95 [0.53–1.60]), ferritin <35 versus ≥35 μg/L (RRR 1.26 [0.72–2.48]) and New York Heart Association class II versus III/IV (RRR 0.91 [0.54–1.56]).

Conclusions

Treatment of iron-deficient HFrEF patients with intravenous iron – namely with ferric carboxymaltose or ferric derisomaltose – results in significant reduction in recurrent HF hospitalizations and cardiovascular mortality. Results were nominally consistent across the subgroups studied, but for several of these subgroups uncertainty remains present.     

Diastolic Dysfunction in Rheumatoid Arthritis: A Meta‐Analysis and Systematic Review

Objective

To determine if the prevalence of diastolic dysfunction is increased in rheumatoid arthritis (RA) patients.

Methods

We conducted a time‐ and language‐restricted literature search to identify studies conducted to compare echocardiographic parameters in patients with RA and controls. The mean difference for echocardiographic variables of interest was calculated using a random‐effects model. A systematic review of the literature was performed.

Results

A total of 25 studies reporting on 5,836 subjects (1,614 with RA) were included. Results reflect mean differences, with positive values denoting higher values in RA patients. Patients with RA had larger mean left atrial dimension (mean difference 0.09 cm [95% confidence interval (95% CI) 0.01, 0.17]; P = 0.02), higher left ventricular mass index (mean difference 6.2 gm/m² [95% CI 1.08, 11.33]; P = 0.02), higher mean systolic pulmonary artery pressure (mean difference 5.87 mm Hg [95% CI 4.36, 7.38]; P < 0.00001), prolonged isovolumetric relaxation time (mean difference 9.67 msec [95% CI 5.78, 13.56]; P < 0.00001), and higher transmitral A wave velocity (mean difference 0.13 meters/second [95% CI 0.07, 0.18]; P < 0.00001) compared to controls. A subanalysis of 2,183 subjects excluding 2 large unmatched studies showed the same results, with the exception that patients with RA had a lower mitral E/A ratio (mean difference ?0.17 [95% CI ?0.25, ?0.09]; P < 0.00001), suggestive of diastolic dysfunction. There were no differences in left ventricular ejection fraction (%), transmitral E wave velocity (meters/second), and mitral deceleration time (msec).

Conclusion

Patients with RA were more likely to have echocardiographic parameters of diastolic dysfunction, and have higher systolic pulmonary artery pressures and larger left atrial sizes.