Effects of nocturnal noninvasive mechanical ventilation on heart rate variability of patients with advanced COPD

BACKGROUND: Cardiovascular comorbidities have a negative impact on the health status and prognosis of patients with COPD. We determined whether nocturnal noninvasive (positive) mechanical ventilation (NIMV) can improve heart rate variability (HRV), decrease circulating natriuretic peptide levels, and improve functional performance of patients with very advanced COPD. METHODS: A randomized, double-blind, parallel controlled trial was conducted in 23 participants with stable but advanced COPD. Participants received standard medical therapy plus nocturnal NIMV or standard medical therapy plus sham NIMV for 3 months. RESULTS: After 3 months of NIMV therapy, the 24-h triangular interpolation of N-N intervals increased from 322 to 473 ms (p = 0.034), the 24-h HRV index (HRVI) increased from 21.8 to 29.9 ms (p = 0.035), nocturnal HRVI increased from 6.1 to 8.0 ms (p = 0.026), and the SD of the average N-N interval increased from 37 to 41 ms (p = 0.020). None of these indexes changed significantly in the control group. Additionally, compared with the control group, the pro-atrial natriuretic peptide levels declined significantly in the NIMV group (p = 0.013). CONCLUSIONS: NIMV applied nocturnally over 3 months may improve HRV, reduce circulating natriuretic peptide levels, and enhance the functional performance of patients with advanced but stable COPD. While not definitive due to small sample size, these data suggest that nocturnal NIMV may reduce the impact of cardiac comorbidities in COPD patients.     

Bronchoalveolar lavage in fibrotic idiopathic interstitial pneumonias

The purpose of this study was to assess the role of bronchoalveolar lavage (BAL) in differentiating usual interstitial pneumonia (UIP) from non-specific interstitial pneumonia (NSIP) and in predicting the prognosis in fibrotic idiopathic interstitial pneumonia (IIP). A retrospective review of 122 patients (age 58+/-8 years, 70 male) with UIP (n=87) and NSIP (n=35) was carried out. Prior to surgical lung biopsy, all of them underwent BAL and high-resolution-computed tomography (HRCT) of the chest. Neutrophil count in BAL fluid was higher in UIP (7.0%) than NSIP (3.0%) (P=0.027). In contrast, BAL lymphocyte count was significantly higher in NSIP (29.0%) than UIP (5.5%) (P<0.0001). In 62 patients whose HRCT findings were atypical for UIP, BAL lymphocytosis was more frequently observed in NSIP (20/33) than UIP (4/29) (P<0.001) and the absence of BAL lymphocytosis suggested a diagnosis of UIP rather than NSIP (odds ratio 12.7, P<0.001). Pathologic diagnosis of NSIP was the only independent factor predicting a longer survival of our patients (median follow-up 21 months) (hazard ratio (HR) 0.035, P=0.005). When NSIP was not included in the survival analysis, higher BAL lymphocyte count was the only independent predictor of a longer survival (HR 0.909, P=0.029). BAL is an useful non-invasive tool in fibrotic IIP, not only for excluding a variety of specific non-IIP diseases but also for narrowing the differential diagnosis and predicting the prognosis in the absence of the histopathologic diagnosis.     

Overview of research on health-related quality of life in patients with chronic liver disease

Health-related quality of life (HRQoL) has become an important outcome measure in patients with chronic liver disease (CLD). In this article, an overview is given of the most common measurement instruments of HRQoL, determinants of HRQoL in patients with CLD, and current developments in the implementation of routine measurement of HRQoL in daily clinical practice. Well-developed generic instruments of HRQoL are the Short Form-36 (SF-36), the Nottingham Health Profile (NHP) and the Sickness Impact Profile (SIP). Well-developed liver disease-specific HRQoL instruments are the Hepatitis Quality of Life Questionnaire (HQLQ), the Chronic Liver Disease Questionnaire (CLDQ), the Liver Disease Quality Of Life Questionnaire (LDQOL ), and the Liver Disease Symptom Index 2.0 (LDSI 2.0). Commonly used HRQoL measures in cost-effectiveness studies are the Health Utilities Index (HUI), Short Form-6D (SF-6D) and the EuroQol-5D (EQ-5D). HRQoL of patients with chronic liver disease has been shown to be impaired, with patients with hepatitis C showing the worst HRQoL. Disease severity, pruritis, joint pain, abdominal pain, muscle cramps, fatigue, depression and anxiety have been associated with HRQoL in patients with CLD. Recently, studies assessing the feasibility and effectiveness of measuring HRQoL in daily clinical practice have been performed, generally showing positive results regarding the discussion of HRQoL-related topics, but mixed results regarding the added value of actual improvement in HRQoL. Furthermore, logistic and attitudinal barriers seem to impede successful implementation. Nevertheless, given the importance of HRQoL in liver patients, we should persist in measuring and subsequently improving HRQoL in clinical practice.     

Artificial Pancreas: Closed-Loop Control of Glucose Variability in Diabetes: Model Predictive Control of Type 1 Diabetes: An in Silico Trial

Background

The development of artificial pancreas has received a new impulse from recent technological advancements in subcutaneous continuous glucose monitoring and subcutaneous insulin pump delivery systems. However, the availability of innovative sensors and actuators, although essential, does not guarantee optimal glycemic regulation. Closed-loop control of blood glucose levels still poses technological challenges to the automatic control expert, most notable of which are the inevitable time delays between glucose sensing and insulin actuation.

Methods

A new in silico model is exploited for both design and validation of a linear model predictive control (MPC) glucose control system. The starting point is a recently developed meal glucose–insulin model in health, which is modified to describe the metabolic dynamics of a person with type 1 diabetes mellitus. The population distribution of the model parameters originally obtained in healthy 204 patients is modified to describe diabetic patients. Individual models of virtual patients are extracted from this distribution. A discrete-time MPC is designed for all the virtual patients from a unique input–output-linearized approximation of the full model based on the average population values of the parameters. The in silico trial simulates 4 consecutive days, during which the patient receives breakfast, lunch, and dinner each day.

Results

Provided that the regulator undergoes some individual tuning, satisfactory results are obtained even if the control design relies solely on the average patient model. Only the weight on the glucose concentration error needs to be tuned in a quite straightforward and intuitive way. The ability of the MPC to take advantage of meal announcement information is demonstrated. Imperfect knowledge of the amount of ingested glucose causes only marginal deterioration of performance. In general, MPC results in better regulation than proportional integral derivative, limiting significantly the oscillation of glucose levels.

Conclusions

The proposed in silico trial shows the potential of MPC for artificial pancreas design. The main features are a capability to consider meal announcement information, delay compensation, and simplicity of tuning and implementation.     

Mathematical Models of the Metabolic System in Health and in Diabetes: GIM, Simulation Software of Meal Glucose�CInsulin Model

Background

A simulation model of the glucose–insulin system in normal life conditions can be very useful in diabetes research, e.g., testing insulin infusion algorithms and decision support systems and assessing glucose sensor performance and patient and student training. A new meal simulation model has been proposed that incorporates state-of-the-art quantitative knowledge on glucose metabolism and its control by insulin at both organ/tissue and whole-body levels. This article presents the interactive simulation software GIM (glucose insulin model), which implements this model.

Methods

The model is implemented in MATLAB, version 7.0.1, and is designed with a windows interface that allows the user to easily simulate a 24-hour daily life of a normal, type 2, or type 1 diabetic subject. A Simulink version is also available. Three meals a day are considered. Both open- and closed-loop controls are available for simulating a type 1 diabetic subject.

Results

Software options are described in detail. Case studies are presented to illustrate the potential of the software, e.g., compare a normal subject vs an insulin-resistant subject or open-loop vs closed-loop insulin infusion in type 1 diabetes treatment.

Conclusions

User-friendly software that implements a state-of-the-art physiological model of the glucose–insulin system during a meal has been presented. The GIM graphical interface makes its use extremely easy for investigators without specific expertise in modeling.     

Diagnosis of intrathoracic lesions: are sequential fine-needle aspiration (FNA) and core needle biopsy (CNB) combined better than either investigation alone?

AIM: To assess the diagnostic accuracy of sequential computed tomography (CT)-guided percutaneous fine-needle aspiration (FNA) and core-needle biopsy (CNB) in comparison with FNA and CNB performed separately for diagnosing intrathoracic lesions. SUBJECTS AND METHODS: Five hundred and eighty-two consecutive patients with thoracic lesions who underwent same-session sequential CT-guided FNA and CNB procedures were studied. The final diagnosis, which was achieved by either agreement of percutaneous procedures with clinical follow-up, bronchoscopy or thoracotomy was available for all cases. The diagnostic yield of the combined FNA+CNB procedures was compared with that of each alone. RESULTS: Adequate samples were obtained in 541 (93%) of FNAs and 513 (88%) of CNBs. Of 582 lesions, 419 (72%) were malignant and 163 (28%) were benign. For malignant lesions, the sensitivity, specificity and accuracy of the procedures were: 376/419 (89.7%), 136/163 (83.4%), and 88% for FNA; 317/419 (75.6%), 138/163 (84.7%), and 78% for CNB; 400/419 (95.5%), 154/163 (94.5%), and 95% for FNA+CNB. The sequential procedures showed significantly better sensitivity, specificity and accuracy compared with either FNA or CNB separately (p<0.003). For the 163 benign lesions, 76 (47%) had a specific benign pathological diagnosis. The diagnosis was obtained in 16/76 (21%) by FNA, in 54/76 (71%) by CNB, and in 60/76 (79%) by FNA+CNB. There was no significant difference between the results of the sequential procedures and CNB alone (p>0.05). CONCLUSIONS: Sequential FNA and CNB improve the diagnostic accuracy of percutaneous CT-guided procedures in malignant lesions. There was only mild improvement, which was not statistically significant, for the diagnosis of benign specific lesions by the sequential procedures compared with the yield of CNB alone.     

Percutaneous Vein Occlusion with Small Intestinal Submucosa: An Experimental Pilot Study in Swine and Sheep

Purpose The objective of this study was to investigate the feasibility, outcomes, and amount of small intestinal submucosa (SIS) material needed for embolization of jugular vein (JV) in a swine and sheep model. Our hypothesis was that SIS would cause vein occlusion. Materials and Methods The external JVs (EJV) in swine (n = 6) and JVs in sheep (n = 6) were occluded with SIS fan-folded compressed strips. After percutaneous puncture of the peripheral portion of the EJV or JV, a TIPS set was used to exit their lumen centrally through the skin. The SIS strips were delivered into the isolated venous segment with a pull-through technique via a 10-Fr sheath. Follow-up venograms were done immediately after placement and at the time of sacrifice at 1 or 3 months. Gross examinations focused on the EJV or JV and their surrounding structures. Specimens were evaluated by histology. Results SIS strip(s) placement was successful in all cases, with immediate vein occlusion seen in 23 of 24 veins (95.8%). All EJVs treated with two strips and all JVs treated with three or four strips remained closed on 1- and 3-month follow-up venograms. Two EJVs treated with one strip and one JV treated with two strips were partially patent on venograms at 1 and 3 months. There has been one skin inflammatory reaction. Necropsies revealed excluded EJV or JV segments with SIS incorporation into the vein wall. Histology demonstrated various stages of SIS remodeling with fibrocytes, fibroblasts, endothelial cells, capillaries, and inflammatory cells. Conclusion We conclude that EJV and JV ablation with SIS strips using percutaneous exit catheterization is feasible and effective in animal models. Further exploration of SIS as vein ablation material is recommended.     

MR imaging of hepatocellular carcinoma: relationship between lesion size and imaging findings, including signal intensity and dynamic enhancement patterns

PURPOSE: To assess the relationship between lesion size and MR imaging findings of pathologically-proven hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In a retrospective, single-center study, 37 consecutive patients were identified between 1999 and 2005 that underwent preoperative MRI and surgical resection of HCC. A total of 47 lesions (mean size = 6.85 cm, range = 1-25 cm) were assessed for signal intensity (SI), enhancement patterns, and secondary morphologic features. Interobserver rating, percentage enhancement, and contrast-to-noise-ratio (CNR) were determined. Lesions were assessed for combinations of typical MRI features. Regression analysis was used to assess relations between MRI findings and tumor size. RESULTS: On fat-suppressed T2-weighted (T2w) fast-spin-echo, smaller lesions had lower SI compared to larger lesions (P < 0.05). In the arterial phase, smaller lesions showed significantly higher percentage enhancement compared to larger lesions (P < 0.05). In the delayed phase, smaller lesions showed less pronounced washout (P < 0.05). Heterogeneity of the lesions, including fatty infiltration, internal nodules, or mosaic pattern, was observed significantly more frequently in larger lesions (P < 0.001). The classic combination of high T2w signal, strong arterial enhancement, and delayed phase washout was present in 23 of 44 lesions (52%). CONCLUSION: Smaller HCC often showed lower SI on T2w, more intense arterial enhancement, and less pronounced delayed washout compared to larger HCC.     

Roles of Neutrophil Gelatinase-Associated Lipocalin in Continuous Ambulatory Peritoneal Dialysis-Related Peritonitis

Introduction  We measured the neutrophil gelatinase-associated lipocalin (NGAL) concentration in peritoneal dialysate effluent (PDE) collected following an acute episode of continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. Results  NGAL concentration in PDE increased in the first 3 days after developing peritonitis and correlated well with the neutrophil count. In patients with culture-negative peritonitis, the NGAL in PDE was lower than that in patients with gram-positive or gram-negative peritonitis. Apart from providing additional diagnostic support to bacterial-induced peritonitis, measurement of NGAL in PDE may be useful to differentiate the neutrophil-dependent culture-negative peritonitis from that associated with non-bacterial or non-cellular etiologies. Conclusion  Human peritoneal mesothelial cell (HPMC) is another source of NGAL during peritonitis. NGAL was specifically induced in HPMC by IL-1β. Incubation of HPMC with recombinant NGAL reversed the transforming growth factor-β-induced up-regulation of Snail and vimentin but rescued the down-regulation of E-cadherin. Our data suggest that NGAL may exert a protective effect in modulating the epithelial-to-mesenchymal transition activated following peritonitis.