A bioadhesive delivery system as an alternative to infiltration anesthesia

Objective. The aim of this study was to determine the feasibility of a novel saliva-activated bioadhesive drug delivery system of lidocaine hydrochloride as a viable alternative to infiltration anesthesia in dentistry.Study design. The study was carried out in three stages. First, the drug delivery system (DDS) was subjectively evaluated for adherence to the gingival mucosa and peak effect of anesthesia. In the second stage, a comparative subjective and objective evaluation of the DDS with a marketed topical gel preparation was carried out. Finally an open label, nonblinded clinical trial was carried out using the exodontia model. A total of 49 extractions were attempted in 41 patients. The effect of the following variables was investigated in the study: (1) jaw (maxillary and mandibular), (2) overall mobility, (3) position-notation of tooth (1, 2, 3, 4…). The positive extractions were statistically analyzed by the t test comparison of means of two independent variables.Results. Subjective evaluation revealed that the DDS adheres to the gingiva within a minute and produces peak effect in 15 minutes. Comparative study revealed that the DDS produces greater depth of anesthesia than the marketed topical gel. Of 49 extractions attempted with the DDS, 40 were successful, giving an efficacy of 81.63%.Conclusion. The novel saliva-activated bioadhesive drug delivery system of lidocaine hydrochloride exhibits potential as a feasible alternative to infiltration anesthesia in dentistry.     

Preoperative Management of Surgical Patients Using Dietary Supplements: Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement

The widespread use of complementary products poses a challenge to clinicians in the perioperative period and may increase perioperative risk. Because dietary supplements are regulated differently from traditional pharmaceuticals and guidance is often lacking, the Society for Perioperative Assessment and Quality Improvement convened a group of experts to review available literature and create a set of consensus recommendations for the perioperative management of these supplements. Using a modified Delphi method, the authors developed recommendations for perioperative management of 83 dietary supplements. We have made our recommendations to discontinue or continue a dietary supplement based on the principle that without a demonstrated benefit, or with a demonstrated lack of harm, there is little downside in temporarily discontinuing an herbal supplement before surgery. Discussion with patients in the preoperative visit is a crucial time to educate patients as well as gather vital information. Patients should be specifically asked about use of dietary supplements and cannabinoids, as many will not volunteer this information. The preoperative clinic visit provides the best opportunity to educate patients about the perioperative management of various supplements as this visit is typically scheduled at least 2 weeks before the planned procedure.     

Pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery

Aim: To test whether short‐term perioperative administration of oral atorvastatin could reduce incidence of postoperative acute kidney injury (AKI) in cardiac surgical patients. Methods: We conducted a double‐blind, randomized controlled trial in 100 cardiac surgical patients at increased risk of postoperative AKI. Patients were randomized to atorvastatin (40 mg once daily for 4 days starting preoperatively) or identical placebo capsule. Primary outcome was to detect a smaller absolute rise in postoperative creatinine with statin therapy. Secondary outcomes included AKI defined by the creatinine criteria of RIFLE consensus classification (RIFLE R, I or F), change in urinary neutrophil gelatinase‐associated lipocalin (NGAL) concentration, requirement for renal replacement therapy, length of stay in intensive care, length of stay in hospital and hospital mortality. Results: Study groups were well matched. For each patient maximal increase in creatinine during the 5 days after surgery was assessed; median maximal increase was 28 µmol/L in the atorvastatin group and 29.5 µmol/L in the placebo group (P = 0.62). RIFLE R or greater occurred in 26% of patients with atorvastatin and 32% with placebo (P = 0.65). Postoperatively urine NGAL changes were similar (median NGAL : creatinine ratio at intensive care unit admission: atorvastatin group 1503 ng/mg, placebo group 1101 ng/mg; P = 0.22). Treatment was well tolerated and adverse events were similar between groups. Conclusion: Short‐term perioperative atorvastatin use was not associated with a reduced incidence of postoperative AKI or smaller increases in urinary NGAL. (ClinicalTrials.gov NCT00910221).     

Biomarkers for early detection of sickle nephropathy

Renal complications affect nearly 30-50% of adults with sickle cell anemia (SCA), causing significant morbidity and mortality. Standard renal function tests like serum creatinine and glomerular filtration rate become abnormal in this disease only when renal damage has become extensive and largely irreversible. Moreover, not all patients develop sickle nephropathy (SN). Therefore, noninvasive biomarkers that predict early onset of SN are necessary. We performed a cross-sectional analysis for nephropathy in 116 patients with sickle cell disease, analyzing urinary kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-b-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and transforming growth factor-β1 (TGF-β), together with conventional renal biomarkers (urine albumin and osmolality, and serum creatinine and cystatin C estimated GFR) during routine clinic visits when patients were at steady-state/baseline. We observed a distinct biomarker pattern: KIM-1 and NAG emerged as biomarkers with a strong association with albuminuria. Surprisingly, and in contrast to other acute/chronic renal disorders, NGAL, L-FABP, and TGF-β levels did not show any relationship with albuminuria in patients with SCA. Our study identifies potential biomarkers for SN, and suggests longitudinal validation of these biomarkers for early detection of SN, so that therapeutic interventions can be applied before renal damage becomes irreversible.     

Pouteria campechiana leaf extract and its bioactive compound myricitrin are mosquitocidal against Aedes aegypti and Culex quinquefasciatus

Objective: To test the mosquitocidal potential of leaf extracts of Pouteria campechiana prepared with different solvents and elucidate the structure of an isolated mosquitocidal compound. Methods: The leaf extracts of Pouteria campechiana prepared with three solvents(petroleum benzene, ethyl acetate and acetone) and potential bioactive fractions were tested against various stages of Aedes aegypti and Culex quinquefasciatus by using the WHO protocols, and the chemical profile and its functional groups were identified by GC-MS and Fourier transmissioninfrared spectroscopy(FT-IR). The structure of bioactive compound was characterized by nuclear magnetic resonance(NMR) spectral technique. Results: The preliminary phytochemical results revealed the presence of alkaloids, amino acids, flavonoids, quinones, saponins, steroids, tannins, and terpenoids in the acetone extract. A significant toxic potential was observed in the acetone extract against both Aedes aegypti and Culex quinquefasciatus mosquitoes. The acetone extract exhibits remarkable larvicidal(LC_(50): 12.232 μg/mL and LC_(90): 63.970 μg/mL), pupicidal(LC_(50): 18.949 μg/mL and LC_(90): 167.669 μg/m L) and adulticidal(LC_(50): 20.689 μg/mL and LC_(90): 72.881 μg/mL) effects against Aedes aegypti. Furthermore, the same extract was subjected to isolation of bioactive compound by GCMS and FT-IR analysis. GC-MS results showed the presence of 5 major compounds, and octacosane(18.440%) was detected as the predominant compound. The FT-IR result of acetone extract demonstrated the presence of various functional groups like alkanes/alkynes, ester, aromatic and amides. The NMR spectrum results of isolated compound were well matched to glycoside linked flavonoids. Based on the chromatography and spectral techniques the isolate molecule was identified as myricitrin by FT-IR and nuclear magnetic resonance spectral data. Conclusion: The isolated compound myricitrin possesses a significant toxic effect in all stages of Aedes aegypti and Culex quinquefasciatus mosquito's with lowest LC_(50) and LC_(90) values.     

Serum Cystatin C Is an Early Predictive Biomarker of Acute Kidney Injury after Pediatric Cardiopulmonary Bypass

Background and objectives: Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). Serum creatinine (SCr), the current standard, is an inadequate marker for AKI since a delay occurs before SCr rises. Biomarkers that are sensitive and rapidly measurable could allow early intervention and improve patient outcomes. We investigated the value of serum cystatin C as an early biomarker for AKI after pediatric CPB.Design, setting, participants, & measurements: We analyzed data from 374 prospectively enrolled children undergoing CPB. Serum samples were obtained before and at 2, 12, and 24 hours after CPB. Cystatin C was quantified by nephelometry. The primary outcome was AKI, defined as a ≥50% increase in SCr. Secondary outcomes included severity and duration of AKI, hospital length of stay, and mortality. A multivariable stepwise logistic regression analysis was used to assess predictors of AKI.Results: One hundred nineteen patients (32%) developed AKI using SCr criteria. Serum cystatin C concentrations were significantly increased in AKI patients at 12 hours after CPB (P < 0.0001) and remained elevated at 24 hours (P < 0.0001). Maximal sensitivity and specificity for prediction of AKI occurred at a 12-hour cystatin C cut-off of 1.16 mg/L. The 12-hour cystatin C strongly correlated with severity and duration of AKI as well as length of hospital stay. In multivariable analysis, 12-hour cystatin C remained a powerful independent predictor of AKI.Conclusion: Serum cystatin C is an early predictive biomarker for AKI and its clinical outcomes after pediatric CPB.Acute kidney injury (AKI) occurs commonly world-wide, affecting 2% to 5% of hospitalized patients and independently predicting mortality and morbidity (1). Once established, the treatment of AKI is largely supportive, at an annual cost surpassing $10 billion in the US alone (2). The diagnosis currently depends on detection of reduced kidney function by a rise in serum creatinine (SCr) concentration, which is a delayed and unreliable measure in the acute setting (3). Notably, experimental studies have identified interventions that may prevent or treat AKI if instituted early in the disease process, well before the SCr rises (4). The lack of early predictive biomarkers has impaired our ability to translate these promising findings to human AKI.Cardiac surgery with cardiopulmonary bypass (CPB) is the most frequent major surgical procedure performed in hospitals worldwide, with well over a million operations undertaken each year. AKI is a common and serious complication encountered in 30% to 40% of adults and children after CPB (5,6). AKI requiring dialysis occurs in up to 5% of these cases, in whom the mortality rate approaches 80% (6). However, even minor degrees of postoperative AKI as manifest by only a 0.2 to 0.3 mg/dl rise in SCr from baseline and often thought to be clinically unimportant, portend a significant increase in short-term mortality in adults (7). AKI after cardiac surgery is also associated with a number of adverse outcomes, including prolonged intensive care and hospital stays, diminished quality of life, and increased long-term mortality (8). Infants and children with congenital heart disease may be especially vulnerable to developing AKI since many require multiple surgeries for stepwise repair of complex congenital anomalies. These patients represent an ideal group for the validation of AKI biomarkers since confounding co-morbid conditions, such as advanced age, pre-existing renal insufficiency, hypertension, atherosclerotic vascular disease, and diabetes are usually absent.Serum cystatin C has been validated as a marker to estimate GFR in several patient populations, including kidney transplants (9) and critically ill patients (10), and more recently has shown promise as an early biomarker of AKI after adult cardiac surgery (11). Cystatin C is an endogenous cysteine proteinase inhibitor produced by nucleated cells at a constant rate. It is freely filtered at the glomerulus, reabsorbed and catabolized, but is not secreted by the tubules. Importantly, cystatin C is readily measurable using clinical laboratory platforms and does not increase with urinary tract infection or in chronic nonrenal disease, such as malignancy.For this study, we sought to (1) determine the accuracy of early serum cystatin C measurements for the prediction of AKI after pediatric CPB; (2) determine the relationship between cystatin C measurements and renal outcomes (duration and severity of AKI); and (3) determine the relationship between cystatin C measurements and clinical outcomes (mortality and length of hospital stay).     

Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI)

Background and objectives

Novel urinary kidney damage biomarkers detect AKI after cardiac surgery using cardiopulmonary bypass (CPB-AKI). Although there is growing focus on whether AKI leads to CKD, no studies have assessed whether novel urinary biomarkers remain elevated long term after CPB-AKI. We assessed whether there was clinical or biomarker evidence of long-term kidney injury in patients with CPB-AKI.

Design, setting, participants, & measurements

We performed a cross-sectional evaluation for signs of chronic kidney injury using both traditional measures and novel urinary biomarkers in a population of 372 potentially eligible children (119 AKI positive and 253 AKI negative) who underwent surgery using cardiopulmonary bypass for congenital heart disease at Cincinnati Children’s Hospital Medical Center between 2004 and 2007. A total of 51 patients (33 AKI positive and 18 AKI negative) agreed to long-term assessment. We also compared the urinary biomarker levels in these 51 patients with those in healthy controls of similar age.

Results

At long-term follow-up (mean duration±SD, 7±0.98 years), AKI-positive and AKI-negative patients had similarly normal assessments of kidney function by eGFR, proteinuria, and BP measurement. However, AKI-positive patients had higher urine concentrations of IL-18 (48.5 pg/ml versus 20.3 pg/ml [P=0.01] and 20.5 pg/ml [P<0.001]) and liver-type fatty acid–binding protein (L-FABP) (5.9 ng/ml versus 3.9 ng/ml [P=0.001] and 3.2 ng/ml [P<0.001]) than did AKI-negative patients and healthy controls.

Conclusions

Novel urinary biomarkers remain elevated 7 years after an episode of CPB-AKI in children. However, there is no conventional evidence of CKD in these children. These biomarkers may be a more sensitive marker of chronic kidney injury after CPB-AKI. Future studies are needed to understand the clinical relevance of persistent elevations in IL-18, kidney injury molecule-1, and L-FABP in assessments for potential long-term kidney consequences of CPB-AKI.