Arterial pulse pressure variation predicting fluid responsiveness in critically ill patients (Retracted article. See vol. 31, pg. 542, 2009)

In critically ill patients, it is important to predict which patients will have their systemic blood flow increased in response to volume expansion to avoid undesired hypovolemia and fluid overloading. Static parameters such as the central venous pressure, the pulmonary arterial occlusion pressure, and the left ventricular end-diastolic dimension cannot accurately discriminate between responders and nonresponders to a fluid challenge. In this regard, respiratory-induced changes in arterial pulse pressure have been demonstrated to accurately predict preload responsiveness in mechanically ventilated patients. Some experimental and clinical studies confirm the usefulness of arterial pulse pressure as a useful tool to guide fluid therapy in critically ill patients.

FGF-23 as a Predictor of Renal Outcome in Diabetic Nephropathy

Background and objectives Fibroblast growth factor 23 (FGF-23) has emerged as a new factor in mineral metabolism in chronic kidney disease (CKD). An important regulator of phosphorus homeostasis, FGF-23 has been shown to independently predict CKD progression in nondiabetic renal disease. We analyzed the relation between FGF-23 and renal outcome in diabetic nephropathy (DN). Design, setting, participants, & measurements DN patients participating in a clinical trial (enalapril+placebo versus enalapril+losartan) had baseline data collected and were followed until June 2009 or until the primary outcome was reached. Four patients were lost to follow-up. The composite primary outcome was defined as death, doubling of serum creatinine, and/or dialysis need. Results At baseline, serum FGF-23 showed a significant association with serum creatinine, intact parathyroid hormone, proteirturia, urinary fractional excretion of phosphate, male sex, and race. Interestingly, FGF-23 was not related to calcium, phosphorus, 25OH-vitamin D, or 24-hour urinary phosphorus. Mean follow-up time was 30.7 +/- 10 months. Cox regression showed that FGF-23 was an independent predictor of the primary outcome, even after adjustment for creatinine clearance and intact parathyroid hormone (10 pg/ml FGF-23 increase = hazard ratio, 1.09; 95% CI, 1.01 to 1.16, P = 0.02). Finally, Kaplan-Meier analysis showed a significantly higher risk of the primary outcome in patients with FGF-23 values of >70 pg/ml. Conclusions FGF-23 is a significant independent predictor of renal outcome in patients with macroalbuminuric DN. Further studies should clarify whether this relation is causal and whether FGF-23 should be a new therapeutic target for CKD prevention. Clin J Am Soc Nephrol 6: 241-247, 2011. doi: 10.2215/CJN.04250510

Early Increase in Myocardial Perfusion After Stem Cell Therapy in Patients Undergoing Incomplete Coronary Artery Bypass Surgery

Incomplete revascularization is associated with worse long-term outcomes. Autologous bone marrow cells (BMC) have recently been tested in patients with severe coronary artery disease. We tested the hypothesis that intramyocardial injection of autologous BMC increases myocardial perfusion in patients undergoing incomplete coronary artery bypass grafting (CABG). Twenty-one patients (19 men), 59 +/- 7 years old, with limiting angina and multivessel coronary artery disease (CAD), not amenable to complete CABG were enrolled. BMC were obtained prior to surgery, and the lymphomonocytic fraction separated by density gradient centrifugation. During surgery, 5 mL containing 2.1 +/- 1.3 x 10(8) BMC (CD34+ = 0.8 +/- 0.3%) were injected in the ischemic non-revascularized myocardium. Myocardial perfusion was assessed by magnetic resonance imaging (MRI) at baseline and 1 month after surgery. The increase in myocardial perfusion was compared between patients with < 50% (group A, n = 11) with that of patients with > 50% (group B, n = 10) of target vessels (stenosis a parts per thousand yenaEuro parts per thousand 70%) successfully bypassed. Injected myocardial segments included the inferior (n = 12), anterior (n = 7), and lateral (n = 2) walls. The number of treated vessels (2.3 +/- 0.8) was significantly smaller than the number of target vessels (4.2 +/- 1.0; P < 0.0001). One month after surgery, cardiac MRI showed a similar reduction (%) in the ischemic score of patients in group A (72.5 +/- 3.2), compared to patients in group B (78.1 +/- 3.2; P = .80). Intramyocardial injection of autologous BMC may help increase myocardial perfusion in patients undergoing incomplete CABG, even in those with fewer target vessels successfully treated. This strategy may be an adjunctive therapy for patients suffering from a more advanced (diffuse) CAD not amenable for complete direct revascularization.

Association between ADAMTS13 polymorphisms and risk of cardiovascular events in chronic coronary disease

Introduction: Association between ADAMTS13 levels and cardiovascular events has been described recently. However, no genetic study of ADAMTS13 in coronary patients has been described. Materials and Methods: Based on related populations frequencies and functional studies, we tested three ADAMTS13 polymorphisms: C1342G (Q448E), C1852G (P618A) and C2699T (A900V) in a group of 560 patients enrolled in the Medical, Angioplasty, or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. The incidence of the 5-year end-points of death and death from cardiac causes, myocardial infarction, refractory angina requiring revascularization and cerebrovascular accident was determined for each polymorphim`s allele, genotype and haplotype. Risk was assessed with the use of logistic regression and Cox proportional-hazards model and multivariable adjustment was employed for possible confounders. Results: Clinical characteristics and received treatment of each genotype group were similar at baseline. In an adjusted model for cardiovascular risk variables, we were able to observe a significant association between ADAMTS13 900V variant and an increased risk of death (OR: 1,92 CI: 1,14-3,23, p = 0,015) or death from cardiac cause (OR: 2,67, CI: 1,59-4,49, p = 0,0009). No association between events and ADAMTS13 Q448E or P618A was observed. Conclusions: This first report studying the association between ADAMTS13 genotypes and cardiovascular events provides evidence for the association between ADAMTS13 900V variant and an increased risk of death in a population with multi-vessel CAD. (C) 2009 Elsevier Ltd. All rights reserved.

Fast-track rehabilitation for lung cancer lobectomy: a five-year experience

Objective: Fast-track rehabilitation is a group of simple measures that reduces morbidity, postoperative complication and accelerates postoperative rehabilitation reducing hospital stay. It can be applied to lung cancer lobectomy. Fast-track rehabilitation cornerstones are: minimally invasive surgical techniques using video-assisted and muscle sparring incisions, normovolemia, normothermia, good oxygenation, euglicemia, no unnecessary antibiotics, epidural patient-controlled analgesia, systemic opiods-free analgesia, early ambulation and oral feeding. Our objective is to describe a five-year experience with fast-track rehabilitation for lung cancer lobectomy. Patients and methods: A retrospective non-controlled study including 109 consecutive patients submitted to fast-track rehabilitation in the postoperative care of lung cancer lobectomy was performed. Only collaborative patients who could receive double-lumen intubation, epidural. catheters with patient-controlled analgesia, who had Karnofsky index of 100, previous normal feeding and ambulation, absence of morbid obesity, diabetes or asthma, were eligible. Postoperative oral feeding and aggressive ambulation started as soon as possible. Results: Immediate postoperative extubation even in the operation room was possible in 107 patients and oral feeding and ambulation were possible before the first hour in 101 patients. Six patients could not receive early oral feeding or ambulate due to hypnosis secondary to preoperative long effect benzodiazepines. Two patients could not ambulate immediately due to epidural catheter misplacement with important postoperative pain. Ninety-nine discharges occurred at the second postoperative day, four of them with a chest tube connected to a Heimlich valve due to air teak. No complication of early feeding and ambulation was observed. Postoperative hypnosis due to long duration benzodiazepines or pain does not allow early oral feeding or ambulation. Avoiding long duration preoperative benzodiazepines, immediate postoperative extubation, regional thoracic PCA and early oral feeding and ambulation were related to a lesser frequency of complication and a shorter hospital stay. Conclusion: Fast-track rehabilitation for lung cancer lobectomies can be safety performed in a selected group of patients if a motivated multidisciplinary group of professionals is available and seems to reduce postoperative complication and hospital stay. (C) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Refractory Angina Cell Therapy (ReACT) Involving Autologous Bone Marrow Cells in Patients Without Left Ventricular Dysfunction: A Possible Role for Monocytes

Autologous bone marrow mononuclear cell (BMMC) transplantation has emerged as a potential therapeutic option for refractory angina patients. Previous studies have shown conflicting myocardium reperfusion results. The present study evaluated safety and efficacy of CellPraxis Refractory Angina Cell Therapy Protocol (ReACT). in which a specific BMMC formulation was administered as the sole therapy for these patients. The phase I/IIa noncontrolled, open label. clinical trial, involved eight patients with refractory angina and viable ischemic myocardium, without left ventricular dysfunction and who were not suitable for conventional myocardial revascularization. ReACT is a surgical procedure involving a single series of multiple injections (40-90 injections, 0.2 ml each) into ischemic areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at 18 months follow-up and myocardium ischemic area reduction (assessed by scintigraphic analysis) at 12 months follow-up, in correlation with a specific BMMC formulation. Almost all patients presented progressive improvement in angina classification beginning 3 months (p = 0.008) postprocedure which was sustained at 18 months follow-up (p = 0.004), as well as objective myocardium ischemic area reduction at 12 months (decrease of 84.4%, p < 0.004). A positive correlation was found between monocyte concentration and CCSAC improvement (r = -0.759, p < 0.05). Improvement in CCSAC, followed by correlated reduction in scintigraphic myocardium ischemic area, strongly suggests neoangiogenesis as the main stem cell action mechanism. The significant correlation between number of monocytes and improvement strongly supports a cell-related effect of ReACT. ReACT appeared safe and effective.

Randomized Study of Surgical Prophylaxis in Immunocompromised Hosts

Although prophylaxis is current practice, there are no randomized controlled studies evaluating preoperative antimicrobial prophylaxis in dental procedures in patients immunocompromised by chemotherapy or organ transplants. To evaluate prophylaxis in dental-invasive procedures in patients with cancer or solid organ transplants, 414 patients were randomized to receive one oral 500-mg dose 2 hours before the procedure (1-dose group) or a 500-mg dose 2 hours before the procedure and an additional dose 8 hours later (2-dose group). Procedures were exodontia or periodontal scaling/root planing. Follow-up was 4 weeks. No deaths or surgical site infections occurred. Six patients (1.4%) presented with use of pain medication > 3 days or hospitalization during follow-up: 4 of 207 (2%) in the 1-dose group and 2 of 207 (1%) in the 2-dose group (relative risk, 2.02; 95% confidence interval, 0.37-11.15). In conclusion, no statistically significant difference occurred in outcome using 1 or 2 doses of prophylactic amoxicillin for invasive dental procedures in immunocompromised patients.

Timing of Dose Relative to Sexual Intercourse Attempt in Previous Sildenafil Citrate Users Treated with Tadalafil: A Geographical Comparison from a Single Arm, Open-Label Study

Introduction. Previous research has demonstrated that sildenafil citrate users alter dosing-sexual attempt behavior when switched to tadalafil. The impact of geography and culture on sexual behavior with phosphodiesterase type 5 (PDE5) inhibitor treatment has not been fully investigated. Aim. To describe and compare the changes in dosing-sexual attempt behavior with sildenafil citrate vs. tadalafil treatment across four distinct geographies: Asia, Australia/New Zealand (ANZ), Central Eastern Europe/Middle East (CEE/ME), and Latin America (LA). Methods. Data from a single-arm, open-label clinical trial conducted in 21 countries from November 2002 to May 2004 were used in this analysis. Men with erectile dysfunction and a history of >= 6-week prior sildenafil citrate use continued sildenafil citrate treatment for 4 weeks then switched to tadalafil for 8 weeks. Dosing instructions were provided. Main Outcomes Measures. Timing of dose and sexual intercourse was assessed through patient diaries for the final 4 weeks of each treatment period. Results. A total of 2,760 men were enrolled: Asia 15.8%; ANZ 29.4%; CEE/ME 19.7%; LA 35.1%. The median time from dosing to intercourse was significantly increased during tadalafil treatment across all geographical regions; however, the magnitude of increase differed significantly by geography (P < 0.0001). The Asian cohort demonstrated the shortest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the least upon switching to tadalafil. The ANZ cohort demonstrated the longest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the most upon switching to tadalafil. Conclusion. Men with a history of established sildenafil citrate use alter their dose-attempt behavior when treated with tadalafil irrespective of geography. However, the extent to which sexual behavior alters is not uniform across geographical regions, suggesting that dosing instructions and duration of drug effectiveness, in combination with personal and cultural preferences, may determine sexual behavior with PDE5 inhibitor use. Rubio-Aurioles E, Glina S, Abdo CHN, Hernandez-Serrano R, Rampazzo C, Sotomayor M, West TM, Gallagher GL, and Lenero E. Timing of dose relative to sexual intercourse attempt in previous sildenafil citrate users treated with tadalafil: A geographical comparison from a single arm, open-label study. J Sex Med 2009;6:2836-2850.

EVALUATION OF FUNCTIONAL GAIN OF THE ELBOW FOLLOWING STEINDLER SURGERY FOR BRACHIAL PLEXUS INJURY

Objective: To evaluate the gain in strength and range of motion after modified Steindler surgery of the elbow in patients with lesions of the upper trunk of the brachial plexus. Method: From 1998 to 2007, eleven patients with traumatic closed upper trunk lesion of the brachial plexus were studied. All the patients had development of at least 1 year of injury and degree of strength of elbow flexion ranging from M1 to M3. The patients underwent Steindler surgery with at least 6 months of follow-up. Pre- and post-operative assessments were carried out to determine gain in muscle strength, range of motion of the elbow, and DASH scale score. Results: Of the eleven patients studied, nine (82%) achieved a level of strength equal to or greater than M3 (MRC) with good functional recovery. Two (18%) reached strength level M2 (MRC). We observed that the patients had an average postoperative gain in range of motion of the elbow of 43.45 degrees. The average elbow flexion after surgery was 88 degrees. There was an improvement in elbow function, as demonstrated in the DASH Scale, in 81% of the patients studied. Conclusion: Modified Steindler surgery was effective in the treatment of patients with injuries of the upper trunk of the brachial plexus, with statistically significant gains in range of motion. In all the cases studied, there was some degree of gain in strength and range of elbow flexion, the gain being correlated with the initial muscle strength. Level of Evidence: Level II, prospective clinical trial.

Program for Prostate Cancer Screening Using a Mobile Unit: Results From Brazil

OBJECTIVES To evaluate the initial results of a prostate cancer screening program using mobile units in Brazil. METHODS Since 2004, we have conducted a program of prostate cancer screening using mobile units across 231 municipalities from 6 Brazilian states. RESULTS A total of 17 571 men were evaluated by clinical history, digital rectal examination (DRE), and serum free and total prostate-specific antigen (PSA) levels. The recommendations for biopsy were a PSA level of >= 4.0 ng/mL, DRE findings suspicious for cancer, or a PSA level of 2.5-4.0 ng/mL with a percent-free PSA level <15%. The biopsy protocol included 12 biopsy cores from the peripheral zone, 2 from the transition zone, and additional sampling of suspicious areas. The cumulative cancer detection rate was 3.7%. The main indication for biopsy was a PSA level of >= 4.0 ng/mL (51.2%), with a positive predictive value (PPV) of 44.1%. Another 19.7% of biopsied men had suspicious DRE findings with a normal PSA level (PPV 23.5%). A percent-free PSA level of <15% in men with a PSA level of 2.5-4.0 ng/mL and normal DRE findings yielded a PPV of 31.1%. The PPV was greater (70.9%) for the 7.1% of men with both suspicious DRE findings and a PSA level of >4.0 ng/mL. Most cancers were Stage T1-T2 (93.4%), and the percentage of Gleason score of >= 7 was 32.5%. The proportion of insignificant cancers according to Epstein`s criteria was 13.5%. CONCLUSIONS A mobile prostate cancer screening unit enabled an underserved population to gain access to specialized care through the public healthcare system. The cancer detection rate in this population was similar to those from international studies. UROLOGY 76: 1052-1057, 2010. (C) 2010 Published by Elsevier Inc.

alpha-Melanocyte Stimulating Hormone Analogue AP214 Protects Against Ischemia Induced Acute Kidney Injury in a Porcine Surgical Model

Purpose: alpha-Melanocyte stimulating hormone protects kidneys against ischemia and sepsis induced acute kidney injury in rodents. We examined the efficacy of a-melanocyte stimulating hormone analogue AP214 to protect against acute kidney injury in higher vertebrates. Materials and Methods: We performed a prospective, blinded, randomized, placebo controlled study in 26 pigs. Laparoscopic technique was used for left nephrectomy and to induce complete warm ischemia in the right kidney for 120 minutes. AP214 (200 mu g/kg intravenously) was administered daily on the day of surgery and for 5 days thereafter. Kidney function was measured for 9 days. We measured changes in serum creatinine, estimated glomerular filtration rate, serum C-reactive protein and urine interleukin-18. Results: In the placebo control and AP214 groups mean peak serum creatinine was 10.2 vs 3.92 mg/dl and the estimated glomerular filtration rate nadir was 22.9 vs 62.6 ml per minute per kg (each p = 0.001). Functional nadir occurred at 72 vs 24 hours in the control vs AP214 groups. Estimated glomerular filtration rate outcome on postoperative day 9 was 118 vs 156 ml per minute per kg in the control vs AP214 groups (p = 0.04). Conclusions: We noted a robust renoprotective effect of AP214. A similar AP214 effect may be observed in humans. Future research includes mechanistic studies in pigs and a phase II human clinical trial of AP214 in kidney transplant and partial nephrectomy populations.

International epidemiology of human pre-existing adenovirus (Ad) type-5, type-6, type-26 and type-36 neutralizing antibodies: Correlates of high Ad5 titers and implications for potential HIV vaccine trials

Replication-defective adenoviruses have been utilized as candidate HIV vaccine vectors Few studies have described the international epidemiology of pre-existing immunity to adenoviruses We enrolled 1904 participants in a cross-sectional serological survey at seven sites in Africa, Brazil, and Thailand to assess neutralizing antibodies (NA) for adenovirus types Ad5, Ad6, Ad26 and Ad36 Clinical trial samples were used to assess NA titers from the US and Europe The proportions of participants that were negative were 14 8%(Ad5), 31 5%(Ad6),41 2%(Ad26) and 53.6% (Ad36) Adenovirus NA titers varied by geographic location and were higher in non-US and non-European settings, especially Thailand In multivariate logistic regression analysis, geographic setting (non-US and non-European settings) was statistically significantly associated with having higher Ad5 titers, participants from Thailand had the highest odds of having high Ad5 titers (adjusted OR = 3 53,95% CI 224,557) Regardless of location. titers of Ad5NA were the highest and Ad36 NA were the lowest Coincident Ad5/6 titers were lower than either Ad5 or Ad6 titers alone Understanding pre-existing immunity to candidate vaccine vectors may contribute to the evaluation of vaccines in international populations (C) 2009 Published by Elsevier Ltd