Effects of an antioxidant protective topical formulation on retinal tissue of UV-exposed rabbits

International Ophthalmology - The aim of this study has been to evaluate the protective effect of a topical antioxidant formulation containing riboflavin, d-α-tocopheryl polyethylene glycol...     

A pilot study of coupled plasma filtration with adsorption in septic shock

OBJECTIVE: To test the hypothesis that nonselective plasma adsorption by a hydrophobic resin (coupled plasmafiltration and adsorption) could improve hemodynamics and restore leukocyte responsiveness in patients with septic shock. DESIGN: Prospective, pilot, crossover clinical trial. SETTING: General intensive care unit in a teaching hospital. SUBJECTS: Ten patients with hyperdynamic septic shock. INTERVENTIONS: Patients were randomly allocated to 10 hrs of either coupled plasma filtration adsorption plus hemodialysis (treatment A) or continuous venovenous hemodiafiltration (treatment B) in random order. We measured the change in mean arterial pressure, norepinephrine requirements, and leukocyte tumor necrosis factor-alpha (TNF-alpha) production (both spontaneous and lipopolysaccharide-stimulated) after 10 hrs of each treatment. We also tested TNF-alpha production from normal human adherent monocytes incubated with patients' plasma obtained before and after the resin, both with or without incubation with an anti-interleukin-10 monoclonal antibody. RESULTS: Mean arterial pressure increased after 10 hr by 11.8 mm Hg with treatment A and by 5.5 mm Hg with treatment B (p =.001). There was an average decrease of norepinephrine requirement of 0.08 microg/kg/min with treatment A and 0.0049 microg/kg/min with treatment B (p =.003). All patients but one survived. Spontaneous and lipopolysaccharide-induced TNF-alpha production from patients' whole blood increased over time with treatment A. This increase was more marked in blood drawn after the device (plasmafiltrate-sorbent plus hemodialyzer) (p =.009). Preresin plasma suppressed lipopolysaccharide-stimulated production of TNF-alpha by 1 x 10(6)cultured adherent monocytes from healthy donors. This suppressive effect was significantly reduced after passage of plasma through the resin (p =.019) and after incubation with anti-interleukin-10 monoclonal antibodies (p =.028). CONCLUSIONS: In patients with septic shock, coupled plasmafiltration-adsorption combined with hemodialysis was associated with improved hemodynamics compared with continuous venovenous hemodiafiltration. This result might be related to its ability to restore leukocyte responsiveness to lipopolysaccharide. These findings suggest a potential role for blood purification in the treatment of septic shock.     

Extracorporal blood purification: more than diffusion and convection. Does this help?

PURPOSE OF REVIEW: A resurgence of interest in adsorbents for medical application is now being seen. In extracorporeal blood purification techniques, the application of unselective adsorbents has been proven to increase remarkably the removal of plasma solutes accumulated as a result of renal and liver failure. RECENT FINDINGS: The present technology for appropriately modifying several intrinsic characteristics of the adsorbents - such as chemical nature, particle and pore-size distribution and the surface area offered to adsorption - has helped to fine-tune extracorporeal devices for more defined clinical applications. These properties, together with improved biocompatibility, have allowed the development of adsorptive techniques to obtain clearances and total removal rates of target compound that would be unthinkable with conventional hemodialysis or hemofiltration. SUMMARY: Despite several adsorptive techniques already being available commercially for treatment of sepsis/septic shock and acute liver failure, controlled studies with clinical end points are still lacking. In the near future it is expected that a final answer to the question in this article's title will be provided.     

The ENCOURAGE mortality risk score and analysis of long-term outcomes after VA-ECMO for acute myocardial infarction with cardiogenic shock

Purpose

This study was designed to identify factors associated with in-intensive care unit (ICU) death and develop a practical mortality risk score for venoarterial-extracorporeal membrane oxygenation (VA-ECMO)-treated acute myocardial infarction (AMI) patients. Long-term survivors’ health-related quality of life (HRQOL), anxiety, depression, and post-traumatic stress disorder (PTSD) frequencies were also assessed.

Methods

Data from 138 ECMO-treated AMI patients admitted to two French ICUs (2008–2013) were analyzed. ICU survivors contacted >6 months post-ICU discharge were assessed for HRQOL, psychological and PTSD status.

Results

Sixty-five patients (47 %) survived to ICU discharge. On the basis of multivariable logistic regression analyses, the ENCOURAGE score was constructed with seven pre-ECMO parameters: age >60, female sex, body mass index >25 kg/m², Glasgow coma score <6, creatinine >150 μmol/L, lactate (<2, 2–8, or >8 mmol/L), and prothrombin activity <50 %. Six months after ECMO, probabilities of survival were 80, 58, 25, 20, and 7 % for ENCOURAGE score classes 0–12, 13–18, 19–22, 23–27, and ≥28, respectively. The ENCOURAGE score ROC AUC [0.84 (95 % CI 0.77–0.91)] was significantly better than those of the SAVE, SAPS II, and SOFA scores. Survivors’ HRQOL evaluated after median follow-up of 32 months revealed satisfactory mental health but persistent physical and emotional-related difficulties, with 34 % (95 % CI 20–49 %) anxiety, 20 % (95 % CI 8–32 %) depression, and 5 % (95 % CI 0–12 %) PTSD symptoms reported.

Conclusions

The ENCOURAGE score might be a useful tool to predict mortality of severe cardiogenic shock AMI patients who received VA-ECMO. However, it now needs prospective validation on other populations of AMI patients.

     

Minimally invasive surgery procedure in isthmic spondylolisthesis

Purpose

The aim of the study was to evaluate the efficacy and safety of the direct lateral approach to the lumbar spine in the treatment of painful isthmic spondylolisthesis in adults.

Methods

Twenty-one patients affected by isthmic spondylolisthesis and treated with extreme lateral interbody fusion and posterior percutaneous pedicle screw fixation were enrolled. All included patients were clinically evaluated with Oswestry Disability Index, SF36 and Visual Scale Anatomy (VAS) for back pain at 1, 3 months and at 1 year.

Results

The mean correction of vertebral slippage measured on lateral lumbar X-ray was 56.3% (p?=?0.002). The average preoperative VAS score was 7.1, at 1 year decreasing to 2.2 (p?=?0.001). The patients had an average preoperative “Oswestry Disability Index” of 36.8 and 24.1% after 1 year (p?=?0.02). The preoperative Short-Form 36 Physical Health was equal to 33.8, 72.1% after 1 month, to 76.3% after 3 months and to 83.2% (p?=?0.001) after 1 year of follow-up. There were no signs of implant loosening at 1-year CT scan examination in any of the patients.

Conclusion

The study showed that the extreme lateral approach to the lumbar spine in case of isthmic spondylolisthesis is a reliable and safe option to the most common open procedures. In the authors’ opinion, XLIF procedures allow a good correction of the listhesis associated with good clinical and radiographic results.

Graphical abstract

These slides can be retrieved under Electronic supplementary material.

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One-week dual therapy with ranitidine bismuth citrate and clarithromycin for the treatment of Helicobacter pylori infection in Brazilian patients with peptic ulcer

AIM: To assess the efficacy and safety of ranitidine bismuth citrate plus clarithromycin given for 1 wk in Brazilian patients with peptic ulcer. METHODS: One hundred and twenty patients with peptic ulcer were randomized in two treatment groups: (1)1-wk regimen consisting of ranitidine bismuth citrate 400 mg b.i.d. with clarithromycin 500 mg b.i.d. or (2) 2-wk regimen of the same treatment. Eradication of the infection was considered when both the histologic examination and the urease test were negative for the infection 3 mo after treatment. RESULTS: By intention to treat analysis, Helicobacter pylori (H pylori) was eradicated in 73% and 76% of patients, respectively treated for 1 or 2 wk (P>0.05). By per protocol analysis, the eradication rates were 80% and 83%, respectively, in patients treated for 1 or 2 wk (P>0.05). Nine patients (8.2%) reported minor side effects. CONCLUSION: One-week therapy with ranitidine bismuth citrate and clarithromycin is safe, well tolerated and effective for treatment of H pylori infection, and appears to be comparable to the 2-wk regimen in terms of efficacy.x     

Regional citrate anticoagulation in critically ill patients treated with plasma filtration and adsorption

BACKGROUND: In high-risk bleeding conditions conventional systemic anticoagulation with heparin is a contraindication to renal replacement therapy. We evaluate the feasibility and safety of regional citrate anticoagulation in high-risk bleeding conditions during coupled plasma filtration adsorption (CPFA). METHODS:Thirteen critically ill patients (9 severely burned, 4 polytraumas) with septic shock and acute renal failure treated with CPFA-CVVHD by using bicarbonate-based solutions (heparin-CPFA group, 58 sessions) or with CPFA-CVVHF using citrate (citrate-CPFA group, 36 sessions). RESULTS: Plasma flow and used cartridges showed no differences between the citrate-CPFA and heparin-CPFA groups, while lost clotted cartridges were significantly lower in the citrate-CPFA group. Blood ionized calcium (iCa2+), Ca2+ infusion, pH and bicarbonates remained constant during citrate-CPFA, with no difference between pre- and post-cartridge plasma citrate. A significant positive correlation between iCa2+ in blood and ultrafiltrate was present. CONCLUSIONS: These suits demonstrate the feasibility and safety of regional citrate anticoagulation in severely burned and polytrauma septic patients treated by CPFA.     

Engineering the specificity of antibacterial fluoroquinolones: benzenesulfonamide modifications at C-7 of ciprofloxacin change its primary target in Streptococcus pneumoniae from topoisomerase IV to gyrase

We have examined the antipneumococcal mechanisms of a series of novel fluoroquinolones that are identical to ciprofloxacin except for the addition of a benzenesulfonylamido group to the C-7 piperazinyl ring. A number of these derivatives displayed enhanced activity against Streptococcus pneumoniae strain 7785, including compound NSFQ-105, bearing a 4-(4-aminophenylsulfonyl)-1-piperazinyl group at C-7, which exhibited an MIC of 0.06 to 0.125 microg/ml compared with a ciprofloxacin MIC of 1 microg/ml. Several complementary approaches established that unlike the case for ciprofloxacin (which targets topoisomerase IV), the increased potency of NSFQ-105 was associated with a target preference for gyrase: (i) parC mutants of strain 7785 that were resistant to ciprofloxacin remained susceptible to NSFQ-105, whereas by contrast, mutants bearing a quinolone resistance mutation in gyrA were four- to eightfold more resistant to NSFQ-105 (MIC of 0.5 microg/ml) but susceptible to ciprofloxacin; (ii) NSFQ-105 selected first-step gyrA mutants (MICs of 0.5 microg/ml) encoding Ser-81-to-Phe or -Tyr mutations, whereas ciprofloxacin selects parC mutants; and (iii) NSFQ-105 was at least eightfold more effective than ciprofloxacin at inhibiting DNA supercoiling by S. pneumoniae gyrase in vitro but was fourfold less active against topoisomerase IV. These data show unequivocally that the C-7 substituent determines not only the potency but also the target preference of fluoroquinolones. The importance of the C-7 substituent in drug-enzyme contacts demonstrated here supports one key postulate of the Shen model of quinolone action.     

Immediate and long-term outcome of recanalization of chronic total coronary occlusions

Eighty-three consecutive patients with 85 coronary total occlusions undergoing coronary angioplasty were retrospectively studied. Patients were divided into two groups according to the occlusion age that was < 30 days (subacute total occlusion [STO]: 25 patients; range 1-30 days) or > 30 days (chronic total occlusion [CTO]: 58 patients; range 3-144 months). All procedures were carried out using a hydrophilic guidewire. Clinical success, consisting of crossing the lesion, balloon dilatation, stent deployment without complications, was 96% in STO and 81% in CTO. Multiple stepwise logistic regression analysis identified a family history of coronary artery disease (CAD), left anterior descending and right coronary artery occlusions as independent predictors of a successful procedure. No major events occurred during or immediately after the angioplasty. After a mean follow-up of 24 +/- 2 months, no difference was found in survival or freedom from myocardial infarction or target vessel revascularization among the STO and CTO patients. Successful recanalization by using a hydrophilic guidewire was achieved in a high percentage of chronic total occlusions with a low incidence of complications and a satisfactory late clinical outcome. Family history of CAD and occlusion of left anterior descending or right coronary arteries are independent predictors of procedural success.     

Development of ocular hypertension secondary to tamponade with light versus heavy silicone oil: A systematic review

Aim:

The intraocular silicone oil (SO) tamponades used in the treatment of retinal detachment (RD) have been associated with a difference ocular hypertension (OH) rate. To clarify, if this complication was associated to use of standard SO (SSO) versus heavy SO (HSO), we performed a systematic review and meta-analysis of comparative study between two kind of SO (standard or light vs. heavy) for the treatment of RD and macular hole, without restriction to study design.

Materials and Methods:

The methodological quality of two randomized clinical trials (RCTs) were evaluated using the criteria given in the Cochrane Handbook for Systematic Reviews of Intervention, while three non-RCTs were assessed with the Newcastle-Ottawa Scale and Strengthening the Reporting of Observational Studies in Epidemiology checklists. We calculated Mantel-Haenszel risk ratio (RR) with 95% confidence intervals (95% CIs). The primary outcome was the rate of patients with OH treated with SSO compared to HSO.

Results:

There were a higher number of rates of OH in HSO compared to SSO. This difference was statistically significant with the fixed effect model (Mantel-Haenszel RR; 1.55; 95% CI, 1.06–2.28; P = 0.02) while there was not significative difference with the random effect model (Mantel-Haenszel RR; 1.51; 95% CI, 0.98–2.33; P = 0.06).

Conclusion:

We noted a trend that points out a higher OH rate in HSO group compared to SSO, but this finding, due to the small size and variable design of studies, needs to be confirmed in well-designed and large size RCTs.