Predictors and outcomes of perioperative blood transfusions in classic bladder exstrophy repair: A single institution study.

BACKGROUND: Primary bladder closure of classic bladder exstrophy (CBE) is a major operation that occasionally requires intraoperative or postoperative (within 72 h) blood transfusions. OBJECTIVE: This study reported perioperative transfusion rates, risk factors for transfusion, and outcomes from a high-volume exstrophy center in primary bladder closure of CBE patients. STUDY DESIGN: A prospectively maintained, institutional exstrophy-epispadias complex database of 1305 patients was reviewed for primary CBE closures performed at the authors' institution (Johns Hopkins Hospital) between 1993 and 2017. Patient and surgical factors were analyzed to determine transfusion rates, risk factors for transfusions, and outcomes. Patients were subdivided into two groups based upon the time of closure: neonatal and delayed closure. RESULTS: A total of 116 patients had a primary bladder closure during 1993-2017. Seventy-three patients were closed in the neonatal period, and 43 were delayed closures. In total, 64 (55%) patients received perioperative transfusions. No transfusion reactions were observed. Twenty-five transfusions were in the neonatal closure group, yielding a transfusion rate of 34%. In comparison, 39 patients were transfused in the delayed closure group, giving a transfusion rate of 91%. Pelvic osteotomy, delayed bladder closure, higher estimated blood loss (EBL), larger pubic diastasis, and longer operative time were all associated with blood transfusion. In multivariable logistic regression, pelvic osteotomy (OR 5.4; 95% CI 1.3-22.8; P < 0.001), higher EBL-to-weight ratio (OR 1.3; 95% CI 1.1-1.6; P = 0.029), and more recent years of primary closure (OR 1.1; 95% CI 1.0-1.2; P = 0.018) remained independent predictors of receiving a transfusion (Summary Table). No adverse transfusion reactions or complications were observed. DISCUSSION: This was the first study from a single high-volume exstrophy center to explore factors that contribute to perioperative blood transfusions. Pelvic osteotomy as a risk factor was unsurprising, as the osteotomy may bleed both during and immediately after closure. However, it is important to use osteotomy for successful closure, despite the increased transfusion risk. The risks accompanying contemporary transfusions are minimal and osteotomies are imperative for successful bladder closure. CONCLUSIONS: More than half of CBE patients undergoing primary closure at a single institution received perioperative blood transfusions. While there was an association between transfusions and osteotomy, delayed primary closure, larger diastasis, increased operative time, and increased length of stay, only the use of pelvic osteotomy, higher EBL-to-weight ratio, and recent year of closure independently increased the odds of receiving a transfusion on multivariate analysis.

Fast high-precision distance metrology using a pair of modulator-generated dual-color frequency combs.

We demonstrate fast high-precision non-contact distance measurements to technical surfaces using a pair of dual-color electro-optic frequency combs for synthetic-wavelength interferometry (SWI). The dual-color combs are generated from continuous-wave (cw) lasers at 1300 nm and 1550 nm, which are jointly fed to a pair of high-speed dual-drive Mach-Zehnder modulators. The dual-color approach is used for continuous and dead-zone-free compensation of temperature-induced fiber drift. We achieve standard deviations below 2 µm at an acquisition time of 9.1 µs for measurements through 7 m of single-mode fiber. Despite the technical simplicity of our scheme, our concept can well compete with other comb-based distance metrology approaches, and it can maintain its accuracy even under industrial operating conditions. The viability of the concept is demonstrated by attaching the fiber-coupled sensor head to an industrial coordinate measuring machine for acquisition of surface profiles of various technical samples. Exploiting real-time signal processing along with continuous fiber drift compensation, we demonstrate the acquisition of point clouds of up to 5 million data points during continuous movement of the sensor head.

The influence of temperature and SRT on high-solid digestion of municipal sewage sludge.

The influence of temperature and solids retention time (SRT) on high-solid digestion of municipal sewage sludge was investigated in laboratory-scale reactors. Digestion with high-solid concentration reduces the required digestion volume and is advantageous for urban areas. The experimental conditions comprised total suspended solids (TSS) in digested sludge between 4.0 and 4.6%, temperatures in a range of 33 to 41 °C and the SRT between 10 and 25 d. High-solid digestion operates with increased NH4-N concentrations released from organic compounds. The anaerobic process can be limited by high NH4-N concentration and toxic NH3. In this study a stable digestion was observed up to 2,000 mg L(-1) NH4-N and 75 mg L(-1) NH3. Volatile suspended solids (VSS) and chemical oxygen demand removal was 53% and 57% respectively. However, digestion with 10 d SRT led to a declined VSS removal of 49%. The removal at 41 and 37 °C showed minor differences, while reduced NH4-N release and reduced methane production were observed at 33 °C. For economic reasons, high-solid digestion at 41 °C is not recommended, but will not impair VSS removal. The outcomes of this study confirm that digestion with up to 7.8% TSS in the feed is feasible for the tested temperatures and SRT down to 15 d.

Performance Boost in Industrial Multifilamentary Nb3Sn Wires due to Radiation Induced Pinning Centers.

We report non-Cu critical current densities of 4. 09 ⋅ 10(9) A/m(2) at 12 T and 2.27 ⋅ 10(9) A/m(2) at 15 T obtained from transport measurements on a Ti-alloyed RRP Nb3Sn wire after irradiation to a fast neutron fluence of 8.9 ⋅ 10(21) m(-2). These values are to our knowledge unprecedented in multifilamentary Nb3Sn, and they correspond to a Jc enhancement of approximately 60% relative to the unirradiated state. Our magnetometry data obtained on short wire samples irradiated to fast neutron fluences of up to 2.5 ⋅ 10(22) m(-2) indicate the possibility of an even better performance, whereas earlier irradiation studies on bronze-processed Nb3Sn wires with a Sn content further from stoichiometry attested a decline of the critical current density at such high fluences. We show that radiation induced point-pinning centers rather than an increase of the upper critical field are responsible for this Jc enhancement, and argue that these results call for further research on pinning landscape engineering.

Neural correlates of 'pessimistic' attitude in depression.

BACKGROUND: Preparing for potentially threatening events in the future is essential for survival. Anticipating the future to be unpleasant is also a cognitive key feature of depression. We hypothesized that 'pessimism'-related emotion processing would characterize brain activity in major depression.MethodDuring functional magnetic resonance imaging, depressed patients and a healthy control group were cued to expect and then perceive pictures of known emotional valences--pleasant, unpleasant and neutral--and stimuli of unknown valence that could have been either pleasant or unpleasant. Brain activation associated with the 'unknown' expectation was compared with the 'known' expectation conditions. RESULTS: While anticipating pictures of unknown valence, activation patterns in depressed patients within the medial and dorsolateral prefrontal areas, inferior frontal gyrus, insula and medial thalamus were similar to activations associated with expecting unpleasant pictures, but not with expecting positive pictures. The activity within a majority of these areas correlated with the depression scores. Differences between healthy and depressed persons were found particularly for medial and dorsolateral prefrontal and insular activations. CONCLUSIONS: Brain activation in depression during expecting events of unknown emotional valence was comparable with activation while expecting certainly negative, but not positive events. This neurobiological finding is consistent with cognitive models supposing that depressed patients develop a 'pessimistic' attitude towards events with an unknown emotional meaning. Thereby, particularly the role of brain areas associated with the processing of cognitive and executive control and of the internal state is emphasized in contributing to major depression.

Effect of nutritional state on Hsp60 levels in the rotifer Brachionus plicatilis following toxicant exposure.

The nutritional state of an organism can affect the results of toxicity testing. Here we exemplified this fact by examining the effect of nutritional deprivation on heat shock protein 60 (hsp60) production in the rotifer Brachionus plicatilis following exposure to two proven inducers of hsp60, a water-accommodated fraction of crude oil (WAF) and a dispersed oil preparation (DO). Both DO and WAF exposures of unfed rotifers resulted in significantly greater hsp60 levels than that of fed DO and WAF exposed rotifers at 8 h: 870 and 3100% of control, respectively. Results clearly demonstrate that a poor nutritional state potentiates stress protein induction upon exposure to water-soluble petroleum products. It is therefore critical to define the organismal nutritional status when reporting toxic responses.

Deficiencies of folate and vitamin B(6) exert distinct effects on homocysteine, serine, and methionine kinetics.

Folate and vitamin B(6) act in generating methyl groups for homocysteine remethylation, but the kinetic effects of folate or vitamin B(6) deficiency are not known. We used an intravenous primed, constant infusion of stable isotope-labeled serine, methionine, and leucine to investigate one-carbon metabolism in healthy control (n = 5), folate-deficient (n = 4), and vitamin B(6)-deficient (n = 5) human subjects. The plasma homocysteine concentration in folate-deficient subjects [15.9 +/- 2.1 (SD) micromol/l] was approximately two times that of control (7.4 +/- 1.7 micromol/l) and vitamin B(6)-deficient (7.7 +/- 2.1 micromol/l) subjects. The rate of methionine synthesis by homocysteine remethylation was depressed (P = 0.027) in folate deficiency but not in vitamin B(6) deficiency. For all subjects, the homocysteine remethylation rate was not significantly associated with plasma homocysteine concentration (r = -0.44, P = 0.12). The fractional synthesis rate of homocysteine from methionine was positively correlated with plasma homocysteine concentration (r = 0.60, P = 0.031), and a model incorporating both homocysteine remethylation and synthesis rates closely predicted plasma homocysteine levels (r = 0.85, P = 0.0015). Rates of homocysteine remethylation and serine synthesis were inversely correlated (r = -0.89, P < 0.001). These studies demonstrate distinctly different metabolic consequences of vitamin B(6) and folate deficiencies.

Single-dose gatifloxacin compared with ofloxacin for the treatment of uncomplicated gonorrhea: a randomized, double-blind, multicenter trial.

BACKGROUND: Treatment of gonorrhea is complicated by widespread resistance of Neisseria gonorrhoeae to antimicrobial agents of choice, including decreased susceptibility to ciprofloxacin. GOAL: To demonstrate the efficacy and safety of gatifloxacin, a novel 8-methoxy fluoroquinolone antibiotic, compared with ofloxacin in treating patients with uncomplicated gonococcal infection. STUDY DESIGN: In a double-blind, randomized (2:2:1), controlled trial, 340 men and 388 women with uncomplicated gonorrhea who were 16 years or older received a single oral dose of gatifloxacin (400 mg or 600 mg) or ofloxacin (400 mg). Primary analysis of efficacy was based on bacteriologic eradication from sites of infection. Secondary analyses examined clinical response and adverse event profiles. RESULTS: Bacteriologic eradication rates for gatifloxacin in evaluable men with urethral gonorrhea were 99% (400 mg) and 100% (600 mg) versus 100% for ofloxacin (n = 117, 122, and 55, respectively; P = ns). Eradication rates in evaluable women with endocervical gonorrhea were 99% for both 400 mg and 600 mg gatifloxacin versus 100% for ofloxacin (n = 101, 104, and 55, respectively; P = ns). Eradication rates were 100% for both rectal (n = 43) and pharyngeal (n = 31) infection across all treatment groups. All three drug regimens were well tolerated and exhibited similar clinical response profiles. CONCLUSION: Gatifloxacin is safe and effective as a single 400-mg or 600-mg dose for the treatment of uncomplicated gonorrhea. Similar efficacy rates were observed with the 400-mg and 600-mg doses. A single 400-mg dose can be recommended for treatment of uncomplicated gonorrhea.

Primed, constant infusion with [2H3]serine allows in vivo kinetic measurement of serine turnover, homocysteine remethylation, and transsulfuration processes in human one-carbon metabolism.

BACKGROUND: One-carbon metabolism involves both mitochondrial and cytosolic forms of folate-dependent enzymes in mammalian cells, but few in vivo data exist to characterize the biochemical processes involved. OBJECTIVE: We conducted a stable-isotopic investigation to determine the fates of exogenous serine and serine-derived one-carbon units in homocysteine remethylation in hepatic and whole-body metabolism. DESIGN: A healthy man aged 23 y was administered [2,3,3-(2)H(3)]serine and [5,5,5-(2)H(3)]leucine by intravenous primed, constant infusion. Serial plasma samples were analyzed to determine the isotopic enrichment of free glycine, serine, leucine, methionine, and cystathionine. VLDL apolipoprotein B-100 served as an index of liver free amino acid labeling. RESULTS: [(2)H(1)]Methionine and [(2)H(2)]methionine were labeled through homocysteine remethylation. We propose that [(2)H(2)]methionine occurs by remethylation with [(2)H(2)]methyl groups (as 5-methyltetrahydrofolate) formed only from cytosolic processing of [(2)H(3)]serine, whereas [(2)H(1)]methionine is formed with labeled one-carbon units from mitochondrial oxidation of C-3 serine to [(2)H(1)]formate to yield cytosolic [(2)H(1)]methyl groups. The labeling pattern of cystathionine formed from homocysteine and labeled serine suggests that cystathionine is derived mainly from a serine pool different from that used in apolipoprotein B-100 synthesis. CONCLUSIONS: The appearance of both [(2)H(1)]- and [(2)H(2)]methionine forms indicates that both cytosolic and mitochondrial metabolism of exogenous serine generates carbon units in vivo for methyl group production and homocysteine remethylation. This study also showed the utility of serine infusion and indicated functional roles of cytosolic and mitochondrial compartments in one-carbon metabolism.

Enteral nutrition in clinical practice.

Enteral nutrition has, at long last, found its place in the modulation of disease. Because of its importance in terms of both anabolic and catabolic processes, today's clinician must have a working knowledge of the types of enteral formulations, their delivery and the therapeutic considerations (particularly concomitant medications) that impact on the safety and efficacy of enteral nutrition. The advantages and disadvantages of this therapeutic intervention must be carefully weighed by the clinician, in concert with sound medical principles. Despite the widespread belief that enteral nutrition is superior to parenteral nutrition in humans, data does suggest that there is little difference between the two. Also, associated costs of enteral nutrition in contrast to parenteral nutrition need to be reappraised based on more invasive enteral access and falling parenteral nutrition prices. Although the enteral route is presumed to be the best feeding modality, the clinician must be ever vigilant about the shortcomings of using the gut, especially in the setting of severe inflammation, stenosis or sepsis. The best feeding modality, then, must blend a knowledge of the patients' anatomy, physiology, and disease with considerations of enteral access, timing of delivery, complications, and a myriad of other therapeutic variables (to include concurrent medication administration) that impact on the enteral feeding regimen. This article reviews the basic principles of enteral nutrition in clinical practice. It describes nutritional assessment, routes of administration, selection of feeding formulas based on nutritional needs, interactions with medications, as well as possible complications of enteral feeding.

Ultrasonographically guided direct gene transfer in utero: successful induction of beta-galactosidase in a rabbit model.

OBJECTIVE: We sought to determine whether the transfer of enzyme-encoding genes in utero can be detected after birth. STUDY DESIGN: An adenoviral vector carrying the gene for beta-galactosidase was injected under ultrasonographic guidance into the livers of 4 rabbit fetuses per litter (3 litters total) at 27 days' gestation. On delivery of the pups 2 to 3 days later, the livers were analyzed for beta-galactosidase activity by using 5-bromo-4-chloro-3-indolyl-beta-D -galactopyranoside (X-gal) staining. Polymerase chain reaction was also performed on liver extracts as an additional independent measure of successful vector delivery. RESULTS: Successful targeting of the livers of fetal rabbits was demonstrated by beta-galactosidase activity in the nuclei of liver serosal cells, parenchymal hepatocytes, or columnar cells of the gallbladder in 7 (58%) of 12 injected pups and by polymerase chain reaction in liver extracts from 10 (83%) of 12 injected pups. CONCLUSIONS: These results suggest that vectors that carry genes for specific enzymes can be delivered to fetal organs in utero and that expression of the enzyme can be detected after delivery.

Symptomatic thrower's exostosis. Arthroscopic evaluation and treatment.

A long-term follow-up was performed on 22 patients treated for a posterior glenoid osteophyte and symptomatic posterior shoulder pain during either the late cocking, acceleration, or follow-through phases of throwing. Arthroscopic evaluation of these patients revealed undersurface tearing of the rotator cuff in all but one. Fifteen patients also had tearing of the posterior labrum. Anterior labral fraying was noted in four patients. Treatment consisted of debridement of the rotator cuff and labral tears. The posterior glenoid osteophyte was removed arthroscopically in 11 patients. Eighteen of 22 throwers treated were available for long-term follow-up at a mean of 6.3 years (range, 1 to 12). Only 10 of 18 (55%) throwers evaluated had returned to their premorbid level of throwing. All 10 were asymptomatic and had maintained a high level of performance for a mean of 3.6 years (range, 1 to 8). At the time of latest follow-up, five players were still participating at the major league level and five had retired. One patient had recurrence of the exostosis 8 years after surgery. Among our patients a trend existed toward a poorer result and failure of return to activity with a posterior osteophyte greater than 100 mm2. A posterior glenoid exostosis, when identified in the symptomatic shoulder of the throwing athlete, can be considered a definite marker of internal impingement.

Rapid atrazine mineralisation in soil slurry and moist soil by inoculation of an atrazine-degrading Pseudomonas sp. strain.

The evaluation of pesticide-mineralising microorganisms to clean-up contaminated soils was studied with the widely applied and easily detectable compound atrazine, which is rapidly mineralised by several microorganisms including the Pseudomonas sp. strain Yaya 6. The rate of atrazine removal was proportional to the water content of the soil and the amount of bacteria added to the soil. In soil slurry, 6 mg atrazine kg soil-1 was eliminated within 1 day after application of 0.3 g dry weight inoculant biomass kg soil-1 and within 5 days when 0.003 g kg soil-1 was used. In partially saturated soil (60% of the maximal water-holding capacity) 15 mg atrazine kg soil-1 was used. In unsaturated soil, about 60% [U-ring-14C] atrazine was converted to 14CO2 within 14 days. Atrazine was very efficiently removed by the inoculant biomass, not only in soil that was freshly contaminated but also in soil aged with atrazine for up to 260 days. The bacteria exposed to atrazine in unsaturated sterile soil were still active after starvation period of 240 days: 15 mg newly added atrazine kg soil-1 was eliminated within 5 days.

A randomized, double-blind clinical trial comparing cefepime plus metronidazole with imipenem-cilastatin in the treatment of complicated intra-abdominal infections. Cefepime Intra-abdominal Infection Study Group.

OBJECTIVE: To evaluate the safety and efficacy of cefepime hydrochloride plus metronidazole vs the combination of imipenem and cilastatin sodium in the treatment of complicated intra-abdominal infections in adult patients. DESIGN: Prospective, randomized, double-blind multicenter study. SETTING: University-affiliated hospitals in the United States and Canada. PATIENTS: Three hundred twenty-three patients with complicated intra-abdominal infections in whom an operative procedure or percutaneous drainage was required for diagnosis and management. INTERVENTION: Cefepime, 2 g, was administered intravenously every 12 hours (n= 164) in addition to metronidazole, 500 mg (or 7.5 mg/kg) intravenously every 6 hours. Imipenen-cilastatin sodium, 500 mg, was administered intravenously every 6 hours (n= 159). Surgical infection management was determined by the patients' surgeons. MAIN OUTCOME ASSESSMENTS: Clinical cure, defined as elimination of all signs and symptoms relevant to the original infection; and treatment failure, defined as persistence, increase or worsening of signs and symptoms resulting in an antibiotic change, requirement of an additional surgical procedure to cure the infection, or a wound infection with fever. RESULTS: Of the initial isolates, 84% were susceptible to cefepime and 92% were susceptible to imipenem-cilastatin. Among the 217 protocol-valid patients, those treated with cefepime+metronidizole were deemed clinical cures (88%) more frequently than were imipenem-cilastatin-treated patients (76%) (P=.02). Using multivariate analysis to adjust for identified clinical risk factors for an adverse outcome (severity of presenting illness, isolation of enterococcus, type of infection, and duration of prestudy hospitalization), there was a trend (P=.06) toward a higher cure rate favoring cefepime+metronidazole. Pathogens were eradicated in significantly (P=.01) more patients treated with combined cefepime and metronidazole (89%) than with imipenem-cilastatin (76%). CONCLUSION: The combination of cefepime plus metronidazole is safe and effective therapy for patients with severe intra-abdominal infections.

Stability of ranitidine and thiamine in parenteral nutrition solutions.

Our objectives were to ascertain the stability of thiamine HCl (3 mg/L) and ranitidine HCl (150 mg/L) at room and refrigeration temperatures in a central vein formula of parenteral nutrition (PN) solution (containing 6% amino acid, 25% carbohydrate, macro- and microminerals, and multivitamins) and to determine the effect of ranitidine on the stability of thiamine. Stability of thiamine and ranitidine in PN solutions was also compared with PN-salt solutions, which contained no amino acids or carbohydrates, to indirectly ascertain the impact of these macronutrients on the stability of these moieties. High-pressure liquid chromatography (HPLC) methods were developed to measure thiamine and ranitidine in the PN mixture. Stability studies were conducted in triplicate and each sample was assayed in duplicate using newly developed HPLC methods. Refrigeration provided stability for both ranitidine and thiamine for extended periods of time. At room temperature, ranitidine was also shown to be stable for about 188 h; there was, however, significant degradation of thiamine at 24 h with, and without, addition of ranitidine. The time required for 10% of thiamine to degrade was calculated to be 12.9 h for the PN mixture containing multivitamins and ranitidine; 11.1 h for the PN mixture containing multivitamins alone; and 33.4 h for the PN mixture containing only thiamine HCl. This work suggests that the concentration of thiamine in this central vein PN formula, with or without ranitidine, falls below the 90% acceptable stability within 24 h.

Natural history and course of acquired lactic acidosis in adults. DCA-Lactic Acidosis Study Group.

STUDY OBJECTIVE: To determine the pathogenesis and clinical course of lactic acidosis in adults receiving standard medical care. DESIGN: Placebo arm of a 5-year prospective, randomized, blinded study comparing placebo and dichloroacetate as specific lactate-lowering therapy. Each patient received intravenous saline placebo in addition to conventional therapy. SETTING: Intensive care units of 10 tertiary care hospitals in North America. PATIENTS: One hundred twenty-six patients with lactic acidosis, defined as arterial blood lactate greater than or equal to 5 mmol/L and either arterial pH of less than or equal to 7.35 or base deficit greater than 6 mmol/L. Patients were followed for up to 6 months. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD demographic entry data for 126 patients included: age 56 +/- 17 years, lactate 10.4 +/- 5.5 mmol/L, pH 7.24 +/- 0.14, calculated base deficit 14.1 +/- 5.4, arterial systolic blood pressure 103 +/- 29 mm Hg, Glasgow Coma score 7.9 +/- 4.9, and APACHE II score 19.2 +/- 8.1. Despite fluids and pressors, 32% of patients had systolic blood pressures of less than or equal to 90 mm Hg in association with sepsis (59%), cardiac failure (18%), or hemorrhage (18%). The most common causes of lactic acidosis in the absence of shock were sepsis (49%), liver disease (15%), and respiratory failure (12%). The median survival was 38.5 hours. Survival at 24 hours was 59%. Arterial pH predicted 24-hour survival better than base deficit or bicarbonate level. Percent survival was 41% at 3 days and 17% at 30 days. Only 21% of patients survived to leave the intensive care unit, and 17% were discharged from the hospital. In patients receiving sodium bicarbonate, neither acid-base nor hemodynamic status improved. CONCLUSIONS: In this first prospective study of the clinical course of acute lactic acidosis in adults, nearly all subjects had both hemodynamic and nonhemodynamic (metabolic) underlying causes, many of which independently predicted survival and most of which were refractory to standard care.