Noninvasive proportional assist ventilation and pressure support ventilation during arm elevation in patients with chronic respiratory failure. A preliminary, physiologic study

BACKGROUND: It has been shown that upper limbs activity increases the respiratory workload in patients with chronic respiratory failure (CRF). The object of the present study was to investigate whether, in these patients: (i) noninvasive positive pressure ventilation (NPPV) could sustain the inspiratory muscles to meet the greater ventilatory demand during upper limbs activity with the arm elevation test (AE); (ii) proportional assist ventilation (PAV) might be superior to pressure support ventilation (PSV) during AE, because of its potential more adaptable response to sudden changes in the ventilatory pattern. METHODS: The study was performed in the pulmonary function laboratory of the Pulmonary Division in Verona General Hospital, Verona, Italy. We studied 8 male patients with CRF due to chronic obstructive pulmonary disease (COPD). Each patient received 2 treatment in random order with a crossover design: spontaneous breathing (SB), SB with AE, either PSV or PAV without and with AE, SB without and with AE, either PSV or PAV without and with AE. We measured: lung function tests, lung mechanics, ventilatory pattern and diaphragmatic effort (pressure time product, PTP(di)). RESULTS: (i) AE increases minute ventilation (+14%) and PTP(di) (+64%); (ii) ventilatory support, both with PSV and PAV unloads the diaphragm both at rest (PTP(di) -77% and -54%, respectively) and during arm elevation (PTP(di) -54% and -44%, respectively). CONCLUSIONS: PAV and PSV unloads the diaphragm in patients with CRF due to COPD both during SB and AE; PAV can be more efficient than PSV in assisting the diaphragm during AE in producing a greater level of minute ventilation for a similar rise in PTP(di) compared to PSV. Noninvasive ventilatory support should be considered in rehabilitation programs for training of upper limbs activity.     

Dialysis patients and cardiovascular problems: Can technology help solve the complex equation?

Patients with end-stage kidney disease undergoing chronic hemodialysis (HD) present higher mortality rates compared with the general population. Once patients are on HD, the risk of cardiovascular death is approximately 30 times higher than in the general population and remains 10-20 times higher after stratification for age, gender, and the presence of diabetes. About half the deaths of patients on dialysis are attributed to cardiovascular causes including coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The cardiovascular burden of the HD patient arises from three different sources: risks inherent to the patient and the uremic syndrome, traditional risk factors, and risk factors related to the dialysis therapy. Based on these considerations and the fact that several aspects of the dialysis procedure can either add to the cardiovascular burden or modify the existing burden, new technologies should be directed towards the approach of a potential 'cardioprotective dialysis therapy'; such an approach may be facilitated by the application of new techniques and advanced dialysis machines. Created to make dialysis easy and safe, new machines feature several options that make patient monitoring and online hemodiafiltration therapy routine procedures. These and other features will possibly make dialysis better tolerated and more efficient in protecting patients from undesirable or potentially fatal cardiovascular events.     

Increased serum resistin in nonalcoholic fatty liver disease is related to liver disease severity and not to insulin resistance

CONTEXT: The recently discovered hormone resistin is linked to the development of insulin resistance, but direct evidence of resistin levels in humans with nonalcoholic fatty liver disease (NAFLD) is lacking. METHODS: We conducted this study to assess the relationship between serum resistin and NAFLD. We measured serum resistin and biochemical, hormonal, and histological correlates in 28 NAFLD patients, 33 controls, and 30 obese patients [body mass index (BMI), >30 kg/m2] without NAFLD. RESULTS: Resistin and adiponectin expression were measured in sc adipose tissue by quantitative RT-PCR. Resistin was higher in NAFLD patients compared with controls (5.87 +/- 0.49 vs. 4.30 +/- 0.20 ng/ml; P = 0.002) and obese patients (4.37 +/- 0.27 ng/ml; P = 0.002). Increased resistin mRNA was also found in the adipose tissue of NAFLD patients compared with controls and obese subjects. CONCLUSIONS: Both NAFLD and obese patients had lower adiponectin levels, whereas leptin was increased only in the obese group. No correlation was found between resistin and high-sensitivity C-reactive protein, BMI, homeostasis model assessment, insulin, glucose, transaminases, and lipid values. A positive correlation was found between resistin and histological inflammatory score. These data report increased resistin in NAFLD patients that is related to the histological severity of the disease, but do not support a link between resistin and insulin resistance or BMI in these patients.     

Transgenic Expression of Cyclin-Dependent Kinase 4 Results in Epidermal Hyperplasia, Hypertrophy, and Severe Dermal Fibrosis

In a previous report we have described the effects of expression of D-type cyclins in epithelial tissues of transgenic mice. To study the involvement of the D-type cyclin partner cyclin-dependent kinase 4 (CDK4) in epithelial growth and differentiation, transgenic mice were generated carrying the CDK4 gene under the control of a keratin 5 promoter. As expected, transgenic mice showed expression of CDK4 in the epidermal basal-cell layer. Epidermal proliferation increased dramatically and basal cell hyperplasia and hypertrophy were observed. The hyperproliferative phenotype of these transgenic mice was independent of D-type cyclin expression because no overexpression of these proteins was detected. CDK4 and CDK2 kinase activities increased in transgenic animals and were associated with elevated binding of p27(Kip1) to CDK4. Expression of CDK4 in the epidermis results in an increased spinous layer compared with normal epidermis, and a mild hyperkeratosis in the cornified layer. In addition to epidermal changes, severe dermal fibrosis was observed and part of the subcutaneous adipose tissue was replaced by connective tissue. Also, abnormal expression of keratin 6 associated with the hyperproliferative phenotype was observed in transgenic epidermis. This model provides in vivo evidence for the role of CDK4 as a mediator of proliferation in epithelial cells independent of D-type cyclin expression.     

Aortic arch shape is not associated with hypertensive response to exercise in patients with repaired congenital heart diseases

Background

Aortic arch geometry is linked to abnormal blood pressure (BP) response to maximum exercise. This study aims to quantitatively assess whether aortic arch geometry plays a role in blood pressure (BP) response to exercise.

Methods

60 age- and BSA-matched subjects – 20 post-aortic coarctation (CoA) repair, 20 transposition of great arteries post arterial switch operation (ASO) and 20 healthy controls – had a three-dimensional (3D), whole heart magnetic resonance angiography (MRA) at 1.5 Tesla, 3D geometric reconstructions created from the MRA. All subjects underwent cardiopulmonary exercise test on the same day as MRA using an ergometer cycle with manual BP measurements. Geometric analysis and their correlation with BP at peak exercise were assessed.

Results

Arch curvature was similarly acute in both the post-CoA and ASO cases [0.05 ± 0.01 vs. 0.05 ± 0.01 (1/mm/m²); p = 1.0] and significantly different to that of normal healthy controls [0.05 ± 0.01 vs. 0.03 ± 0.01 (1/mm/m²), p < 0.001]. Indexed transverse arch cross sectional area were significantly abnormal in the post-CoA cases compared to the ASO cases (117.8 ± 47.7 vs. 221.3 ± 44.6; p < 0.001) and controls (117.8 ± 47.7 vs. 157.5 ± 27.2 mm²; p = 0.003). BP response to peak exercise did not correlate with arch curvature (r = 0.203, p = 0.120), but showed inverse correlation with indexed minimum cross sectional area of transverse arch and isthmus (r = -0.364, p = 0.004), and ratios of minimum arch area/ descending diameter (r = -0.491, p < 0.001).

Conclusion

Transverse arch and isthmus hypoplasia, rather than acute arch angulation plays a role in the pathophysiology of BP response to peak exercise following CoA repair.     

Search for poliovirus long-term excretors among patients affected by agammaglobulinemia

Patients with agammaglobulinemia may excrete enteroviruses, including vaccine-derived poliovirus, for prolonged periods of time. This poses a risk to the patients but it also may pose a risk to the population after eradication of poliovirus and the cessation of routine vaccination. To assess this risk, a pilot study was performed to identify potential poliovirus long-term excretors in a cohort of 38 patients with a definite/presumptive diagnosis of X-linked agammaglobulinemia (XLA). Stool samples were analyzed to detect any polio or other enteroviruses replicating in the gut and neutralizing antibodies against polioviruses were measured in the sera. No viruses were isolated from the stool samples and most sera had neutralizing antibody levels against all three poliovirus serotypes considered by the WHO to be protective in immunocompetent individuals. This suggests that long-term excretion of enteroviruses in patients with agammaglobulinemia is relatively uncommon.     

The glucose dysmetabolism in the acute phase of non-diabetic ST-elevation myocardial infarction: from insulin resistance to hyperglycemia

In the setting of acute myocardial infarction, hyperglycemia and acute insulin resistance may represent a stress response to myocardial injury mainly related to acute catecholamine release. By measuring glucose values and insulin resistance (Homeostatic Model Assessment index—HOMA), we evaluated in 356 non-diabetic patients with ST-elevation myocardial infarction (STEMI) undergone mechanical revascularization: (a) the acute glycometabolic response by evaluating insulin resistance, glucose levels, and their combination and (b) whether insulin resistance and increased glucose values (and their combination) are able to affect in-Intensive Cardiac Care Unit (ICCU) mortality and complications. In the overall population, 226 (63.5%) patients showed glucose values ≤140 mg/dl (group B), while 130 patients had glucose values >140 mg/dl (group A) (36.5%). Within group B, insulin resistance (as inferred by positive HOMA index) was present in 125 patients (55.3%), whereas 101 patients (44.7%) exhibited normal values of HOMA index. Within group A, 109 patients (83.8%) were insulin resistant, while 21 patients (16.2%) had normal values of HOMA index. At multivariable analysis, glucose values were independently associated with in-ICCU mortality (OR: 7.387; 95% CI 2.701–20.201; P < 0.001) and complications (OR: 1.786; 95% CI 1.089–2.928; P = 0.022). In the early phase of STEMI, the acute glycometabolic response to stress is heterogeneous (ranging from no insulin resistance to glucose levels >140 mg/dl and, finally, to the combination of increased glucose values and insulin resistance). Increased glucose values are stronger prognostic factors since they are independently associated with in-ICCU mortality and complications.     

The p53 codon 72 (Arg72Pro) polymorphism is associated with the degree of insulin resistance in type 2 diabetic subjects: a cross-sectional study

Tumor suppressor protein p53 has been demonstrated to regulate genes involved in energy generating metabolic pathways and apoptosis. To date, a new field of research is the involvement of TP53 codon 72 (Arg72Pro) polymorphism in the diabetic disease. The aim of this study was to evaluate whether the genotype and the related genetic models of Arg72Pro polymorphism of TP53 (rs1042522) are associated with insulin resistance and its metabolic parameters in diabetic and non-diabetic subjects. We examined 335 type 2 diabetic patients (65.5 ± 8.4 years) and 367 non-diabetic subjects (60.5 ± 11.7 years). The results were validated in a validation sample consisting of 199 type 2 diabetic (66.2 ± 8.5 years) and 224 non-diabetic subjects (61.2 ± 12.7 years). In the study sample, the analysis of covariance, adjusted for the effects of age, gender and BMI, showed a significant genotype–diabetes effect on insulin resistance evaluated by HOMA-IR (p = 0.038). This result was mediated by variations in fasting plasma insulin (p = 0.027), as no TP53 genotype–diabetes effects were detected for fasting plasma glucose. In particular, in the diabetic subjects, Pro/Pro genotype was associated with lower values of HOMA-IR with respect to Arg/Arg (p = 0.013) and Arg/Pro (p = 0.006) carriers. No difference in HOMA-IR between diabetic and non-diabetic Pro/Pro carriers was found. Significant recessive model–diabetes interaction effects on fasting insulin and HOMA-IR adjusted for age, sex and BMI were found (p = 0.007 and p = 0.029, respectively). Linear regression analyses, based on the assumption of an additive genetic model adjusted for age, sex and BMI, highlight p53 gene–diabetes interaction effects on fasting insulin (β = ?1.27; p = 0.001) and HOMA-IR (β = ?0.22; p = 0.006). The results of statistical analyses on fasting insulin and HOMA-IR were all confirmed in the validation sample. Furthermore, the logistic regression models confirmed that the effect of HOMA-IR levels on diabetes was moderated by Pro/Pro genotype in both study and validation samples (OR = 0.29, p = 0.034, 95 % CI = 0.09–0.91, OR = 0.37, p = 0.035, 95 % CI = 0.15–0.93, respectively). Our findings suggest that p53 codon 72 (Arg72Pro) polymorphism influences insulin resistance in type 2 diabetic patients independently of body mass.