Airway Occlusion Pressure to Titrate Positive End-expiratory Pressure in Patients with Dynamic Hyperinflation

Background: Although the use of external positive end-expiratory pressure (PEEP) is recommended for patients with intrinsic PEEP, no simple method exists for bedside titration. We hypothesized that the occlusion pressure, measured from airway pressure during the phase of ventilator triggering (P0.1t), could help to indicate the effects of PEEP on the work of breathing (WOB).

Methods: Twenty patients under assisted ventilation with chronic obstructive pulmonary disease were studied with 0, 5, and 10 cm H2O of PEEP while ventilated with a fixed level of pressure support.

Results: PEEP 5 significantly reduced intrinsic PEEP (mean +/- SD, 5.2 +/- 2.4 cm H2O at PEEP 0 to 3.6 +/- 1.9 at PEEP 5;P < 0.001), WOB per min (12.6 +/- 6.7 J/min to 9.1 +/- 5.9 J/min;P = 0.003), WOB per liter (1.2 +/- 0.4 J/l to 0.8 +/- 0.4 J/l;P < 0.001), pressure time product of the diaphragm (216 +/- 86 cm H2O [middle dot] s-1 [middle dot] min-1 to 155 +/- 179 cm H2O [middle dot] s-1 [middle dot] min-1;P = 0.001) and P0.1t (3.3 +/- 1.5 cm H2O to 2.3 +/- 1.4 cm H2O;P = 0.002). At PEEP 10, no further significant reduction in muscle effort nor in P0.1t (2.5 +/- 2.1 cm H2O) occurred, and transpulmonary pressure indicated an increase in end-expiratory lung volume. Significant correlations were found between WOB per min and P0.1t at the three levels of PEEP (P < 0.001), and between the changes in P0.1tversus the changes in WOB per min (P < 0.005), indicating that P0.1t and WOB changed in the same direction. A decrease in P0.1 with PEEP indicated a decrease in intrinsic PEEP with a specificity of 71% and a sensitivity of 88% and a decrease in WOB with a specificity of 86% and a sensitivity of 91%.     

Inhibition of paraquat-induced autophagy accelerates the apoptotic cell death in neuroblastoma SH-SY5Y cells.

Autophagy is a degradative mechanism involved in the recycling and turnover of cytoplasmic constituents from eukaryotic cells. This phenomenon of autophagy has been observed in neurons from patients with Parkinson's disease (PD), suggesting a functional role for autophagy in neuronal cell death. On the other hand, it has been demonstrated that exposure to pesticides can be a risk factor in the incidence of PD. In this sense, paraquat (PQ) (1,1'-dimethyl-4,4'-bipyridinium dichloride), a widely used herbicide that is structurally similar to the known dopaminergic neurotoxicant MPP(+) (1-methyl-4-phenyl-pyridine), has been suggested as a potential etiologic factor for the development of PD. The current study shows, for the first time, that low concentrations of PQ induce several characteristics of autophagy in human neuroblastoma SH-SY5Y cells. In this way, PQ induced the accumulation of autophagic vacuoles (AVs) in the cytoplasm and the recruitment of a LC3-GFP fusion protein to AVs. Furthermore, the cells treated with PQ showed an increase of the long-lived protein degradation which is blocked in the presence of the autophagy inhibitor 3-methyladenine and regulated by the mammalian target of rapamycin (mTOR) signaling. Finally, the cells succumbed to cell death with hallmarks of apoptosis such as phosphatidylserine exposure, caspase activation, and chromatin condensation. While caspase inhibition retarded cell death, autophagy inhibition accelerated the apoptotic cell death induced by PQ. Altogether, these findings show the relationship between autophagy and apoptotic cell death in human neuroblastoma cells treated with PQ.     

In a randomized controlled trial, cataract surgery in both eyes increased benefits compared to surgery in one eye only

BACKGROUND AND OBJECTIVE: Despite recommendation of surgery in both eyes in patients with bilateral cataract, there is little evidence about the benefits of second-eye surgery. The objective of this study was to compare the benefits of cataract surgery in both eyes with those of surgery in one eye only. STUDY DESIGN AND SETTING: Two-arm randomized controlled trial involving 296 patients with bilateral cataracts of two public teaching hospitals. Patients were randomly assigned to receive surgery in one eye only (control group) or surgery in both eyes, one eye at a time (intervention group). The main outcome measures were binocular visual acuity, binocular contrast sensitivity, stereopsis, and patient-reported visual disability (VF-14), measured 4-6 months postoperatively. RESULTS: A total of 135 (91.2%) and 139 (93.9%) patients completed the trial in the control and intervention groups, respectively. Postoperatively, intervention group presented a better visual acuity (difference of 0.07; 95% CI = 0.03, 0.12), stereopsis (0.62 log sec arc; 95% CI = 0.45, 0.79), and VF-14 (8.2 points; 95% CI = 4.4, 12.4). No significant differences were found for contrast sensitivity. CONCLUSIONS: Bilateral cataract patients should have surgery in both eyes. Including stereopsis and patient-reported visual disability in the assessment of cataract patients, especially after first-eye surgery, will improve the evaluation of effectiveness.     

Consequences of using different methods to assess cardiovascular risk in primary care

BACKGROUND: There are two promising methods to assess cardiovascular risk: the Adult Treatment Panel III (ATPIII) and the Systematic Coronary Risk Evaluation (SCORE). The ATPIII calculates the 10-year risk of coronary events based on an adaptation of the original Framingham function. The SCORE chart is based on European studies and measures the absolute risk of cardiovascular mortality in the next 10 years. OBJECTIVE: To evaluate the clinical consequences of using different methods to calculate cardiovascular risk and different primary prevention guidelines. METHODS: A cross sectional study of 914 dyslipidemic patients from three primary health centres from Catalonia, Spain, was conducted. Outcome variables were the risk level according to the different equations (classical Framingham table by Anderson, ATPIII adapted Framingham table, and SCORE system), and candidates for lipid lowering treatment according to European and ATPIII guidelines. RESULTS: The proportion of high-risk patients according to the three equations and excluding diabetic patients was 13.5%, 11.4% and 7.1%, respectively, and 20.2%, 25.7% and 29.2%, respectively when including diabetic patients. The prevalence of candidates for lipid lowering treatment according to European guidelines and ATPIII guidelines were 28.8% and 39.3%, respectively. A 49% disagreement with a Kappa of -0.1, and a 37% disagreement with a Kappa of 0.08 were observed when comparing candidates identified for lipid lowering treatment and patients actually receiving that treatment, according to ATPIII and SCORE guidelines, respectively. CONCLUSION: Our results suggest important clinical and economic consequences when comparing European guidelines or ATPIII guidelines for the treatment of dyslipidemic patients in general practice.     

Early experience of a living donor kidney transplant program

OBJECTIVES: Laparoscopic nephrectomy has been shown to reduce the morbidity of live donor nephrectomy, but post-transplant kidney function and safety issues with the procedure are still of some concern. The review of our early experience could detect errors that should be avoided in the refining of the technique. METHODS: Our first sixty consecutive laparoscopic donor nephrectomies were analyzed retrospectively. RESULTS: There were conversions to open surgery (5%), all three in the first 18 cases. All donors were alive at 1 year with a glomerular filtration rate of 85+/-21 ml/min (78% of the basal). Patient and graft survival at 1 year was 100% and 95%, respectively. Creatinine nadir was achieved on post-transplant day 3 (creatinine, 176+/-122 micromol/l). Late renal function proved a continuous improvement until the 2-year follow-up (creatinine, 135+/-29 micromol/l). Renal function recovery was better in both recipient and donor when the donor was < or =50 years old, compared with older patients. Transplant complications that required reintervention included one ureteral fistula, one ureteral stenosis and one case of low renal flow that was re-vascularised. CONCLUSIONS: Technical surgical aspects such the use of Haemoloc clips in the clipping of the artery, the hand-assisted extraction of the kidney, a refined surgical technique during the transplant and avoidance of prolonged warm and cold ischemia, taken together with an adequate intraoperative hemodynamic management of the donor aid in avoiding life-threatening complications and achieving a good post-transplant renal function recovery.