Characteristics of Participants in the American Urological Association Quality (AQUA) Registry and Early Impact of Participation on Quality of Care.

INTRODUCTION: The American Urological Association Quality Registry (AQUA) is an approved Qualified Clinical Data Repository that was created in 2013 to serve as a platform of quality assessment and improvement. Little is known about how such specialty specific platforms are adopted and used. We describe AQUA participants and report early impact on quality metrics. METHODS: We compared characteristics of practices and urologists participating in AQUA from 2014-2017 to those of the broader urologist workforce as reported in the 2017 American Urological Association Census, and examined pass rates of 4 measures reported to the Centers for Medicare and Medicaid Services after participation in AQUA. RESULTS: Participation increased during the first 4 years and included >125 practices and 1,148 urologists (9.2% of practicing U.S. urologists). Of AQUA participants 97.6% were in private practice, 1.9% were in academic practice and the rest (0.5%) were employed by private or public hospitals, compared to 59.1%, 25.5% and 11.2%, respectively, of urologists nationally. Among AQUA participants 95.9% lived in metropolitan areas, compared to 89.9% of urologists nationally. A total of 17 quality measures were reported to the Centers for Medicare and Medicaid Services through AQUA, of which 4 were urology specific and 13 were crosscutting. The average pass rate across the 4 select urological measures was 31.1% prior to AQUA dashboard access and 48.8% after access was gained, a 56.9% improvement (17.1% absolute difference). CONCLUSIONS: Early participants in AQUA were mostly community practitioners. Participation in AQUA seemed to facilitate quality score improvements, although whether this was due to improved measurement vs clinical care is unknown at this time.

The correlation of adhesions and peritoneal fluid cytokine concentrations: a pilot study.

BACKGROUND: Intra-abdominal adhesion formation and reformation after surgery is a significant cause of morbidity. The greatest problem after the surgical removal of adhesions is their reformation. We examined the concentrations of interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha in the peritoneal fluid throughout the 48 h post-operative period following adhesiolysis, and correlated the results to the extent of adhesion reformation. METHODS: Peritoneal fluid, collected from eight patients following laparoscopy and again at 12, 36 and 48 h after surgery, was analysed using enzyme-linked immunosorbent assay (IL-1 and IL-6) and bioassay (TNF-alpha). At 48 h, a second look laparoscopy was performed to inspect the pelvis for adhesion formation/reformation. RESULTS: Three patients had adhesion reformation >10% at 48 h after surgery. The mean adhesion score 48 h after adhesiolysis was 5 (range 0-17). The mean reduction in adhesion score was 88% (range 83-100%). Newly formed adhesions were filmy, relatively soft and avascular in nature. Adhesion reformation of >10% was associated with (i) high concentrations of IL-6 at 12 h (P < 0.01) and (ii) high concentrations of IL-1 at 48 h (P < 0.001). CONCLUSIONS: Results from this preliminary study suggest that future treatment strategies for adhesion prevention could be aimed at the control of cellular mediators in the peritoneal fluid during the initial adhesion formation period.

IL-1, IL-6 and TNF-alpha concentrations in the peritoneal fluid of women with pelvic adhesions.

BACKGROUND: Pelvic adhesions are a significant cause of morbidity and are associated with infertility and pain. The three pro-inflammatory cytokines interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha are involved in adhesion formation/reformation. METHODS: The concentration of these three cytokines was examined in the peritoneal fluid of women undergoing laparoscopy, in order to examine the factors affecting their concentrations, with specific reference to the presence or absence of adhesions. RESULTS: We found that the concentration of TNF-alpha in the peritoneal fluid was significantly correlated to the menstrual cycle day (P < 0.01), with increasing concentration as the menstrual cycle progressed from the follicular to the luteal phase. In contrast, IL-1 and IL-6 levels did not show any variation throughout the menstrual cycle. Increased TNF-alpha was found in patients with pelvic adhesions compared with those with normal pelvis; the concentration of TNF-alpha was highest in mild compared with severe adhesions. In contrast, IL-1 concentration was higher in the presence of severe adhesions. IL-6 levels were significantly correlated with the grade of endometriosis (P < 0.05), but there were no significant correlations of either TNF-alpha or IL-1 concentrations with the various grades of endometriosis. CONCLUSION: The exact role of TNF-alpha and IL-1 in adhesion formation is still unknown, but the results from this study suggest that their concentration in the peritoneal fluid is associated with the degree of adhesions present.

Peritoneal healing and adhesion formation/reformation.

Intra-abdominal adhesion formation and reformation after surgery is a cause of significant morbidity, resulting in infertility and pain. The understanding of the pathogenesis of adhesion formation and reformation especially at the cellular and molecular level can help to further develop more effective treatments for the prevention of adhesion formation and reformation. Following an injury to the peritoneum, fibrinolytic activity over the peritoneal surface decreases, leading to changes in the expression and synthesis of various cellular mediators and in the remodelling of the connective tissue. The cellular response to peritoneal injury and adhesion formation and reformation are reviewed. Analysis of the available literature data on the cellular mediators in the peritoneal fluid showed variation in results from different investigators. The potential sources of variability and error are examined. It is still unclear if there is significant individual variation in the peritoneal response to injury.

Splenic B cell lymphoma with lymphocyte clusters in peripheral blood smears.

EDTA induced clumping of lymphoid cells, both benign and malignant, in peripheral blood samples has been reported only rarely. Such clustering presents the laboratory and pathologist with unique difficulties in the accurate diagnosis of these disorders. A case of low grade B cell splenic lymphoma is presented with lymphocyte clumping in smears made from EDTA anticoagulated peripheral blood, the fourth case described in which neoplastic lymphoid cells form clusters in vitro in peripheral blood. The association with splenic lymphomas (three of the four cases) is intriguing but its significance remains uncertain.

The incidence of unexpected antibodies in blood products collected at a military donor center.

The objective of the study was to determine the frequency of unexpected antibodies in a population of Air Force personnel thought to be representative of the population involved in combat situations. Recipients of blood transfusions in combat situations may not be screened for the presence of unexpected (non-A, non-B) antibodies. The records of the Wilford Hall Medical Center/59th Medical Defense Wing Donor Center and Transfusion Medicine Laboratory were reviewed for the calendar years 1995 and 1996 to determine the frequency of unexpected antibodies in this center's donor population, the vast majority of whom are Air Force basic trainees. The frequency of unexpected antibodies in the basic trainee donor population was 4/10,000. Clinically significant antibodies were present in 2/10,000. Because this donor pool probably represents the potential population of combat casualties, this information is reassuring in assessing the risks associated with blood transfusion in combat situations.

Merkel cell carcinoma of the lower lip: a case report and histopathologic study.

Merkel cell carcinoma of the lower lip is a rare clinical entity. It is generally thought to be more aggressive than the more common skin cancers of the lips and oral cavity. The literature reveals that delayed diagnoses and poor survival are common among patients with these malignancies. Recommended treatment is surgical excision with wide margins and treatment of cervical metastases with either surgery or radiotherapy or both. Unlike other malignant neoplasms, the occurrence of Merkel cell carcinoma in a relatively older population makes comorbid conditions a key factor in treatment planning.

Beta-cluster haplotypes, alpha-gene status, and hematological data from SS, SC, and S-beta-thalassemia patients in southern California.

The beta-gene-cluster haplotype and alpha-gene status were determined for 221 patients with sickle cell anemia, 41 with SC disease, and 21 with S-beta-thalassemia. Among SS patients, eleven beta S haplotypes were found in 21 combinations. Three haplotypes--the Benin (Ben) [---+-], the Central African Republic (CAR) [+---+], and the Senegal (Sen) [+- ]--comprise 61%, 21%, and 10% of the chromosomes, respectively. Cleavage at the Xmn I site 5' to the G gamma gene was observed only when the Senegalese arrangement was present. The linear correlation which exists between the absolute value of the G gamma chains and the Hb F for each haplotype combination suggests a feed-back mechanism which controls the G gamma to A gamma ratio and thus the Hb F level (or vice versa). The A gamma T chain was present with specific haplotypes [++-++] and [++-+-]. Heterozygous or homozygous alpha-thalassemia-2 was present in 36% of the SS patients and was randomly distributed among beta S-gene-cluster haplotypes. The variable levels of hemoglobin, MCV, Hb F, G gamma chains, and Hb A2 are in response to the heterogeneous genetic mix of the beta S-gene-cluster haplotypes and alpha-thalassemia-2 in American patients with sickle cell anemia. The influence of alpha-thalassemia-2 on the level of Hb F is dependent on the beta S-cluster haplotype. Hb A2 levels increased with decrease in the number of alpha genes. Among SC and S-beta-thalassemia patients the beta-cluster polymorphisms on the beta S chromosome were those commonly associated with the African origins of beta S haplotype. The haplotype [+--+-] was present on the C chromosome in 90% of the cases. Most beta-thalassemia chromosomes had haplotypes that matched the common African polymorphisms. An alpha-gene deletion was found in 29% of the SC and S-beta-thalassemia patients.

A study of the minor peaks in high performance liquid chromatograms of globin chains on reversed phase columns.

The high performance liquid chromatograms of the hemoglobins in a hemolysate show minor peaks on reversed phase columns in addition to the expected major peaks of the alpha, beta, and gamma chains. One of these had previously been identified as the delta chain. The material in the most prominent minor peak which is termed "pre-beta" is indistinguishable from the normal beta chain in amino acid composition, but the difference has not been identified. An analogous pre-delta peak appears when chromatographically isolated Hb A2 is examined, but pre-alpha and pre-gamma peaks have not been observed. One minor peak contains a non-heme protein(s). Glycosylated hemoglobins do not separate from their non-glycosylated counterparts, but acetylated gamma chains appear to do so.

The estimation of Hb A2 in the presence of Hb C or Hb E by reverse phase high performance liquid chromatography.

Although Hb-C may be separated from Hb A2 by some ion exchange methods, most will not separate Hb E and Hb A2. The delta chain can be readily separated from the beta C, beta E and beta O-Arab chains by reverse phase HPLC. Hence, reverse phase HPLC provides a means of quantitatively determining Hb A2 in the presence of Hb C, Hb E, and Hb O-Arab. The procedure, although not highly accurate, does permit the detection of increased Hb A2, for example, in beta-thal heterozygotes and, therefore, is applicable to other conditions (Hb C, Hb E, Hb O-Arab).

Hb Aztec or alpha 2 76 (EF5) Met----Thr beta 2 detection of a silent mutant by high performance liquid chromatography.

High performance liquid chromatography has detected 14 abnormal hematological states in 600 randomly selected samples of blood. Two of these are silent mutations which are not apparent from chromatographic or electrophoretic examination. One of these has the substitution alpha 76 (EF5) Met----Thr and has been named Hb Aztec. The variant was first detected in a 9-day-old baby girl who had inherited it from her mother. This abnormal hemoglobin has no obviously deleterious effect on hematological status or health.

High performance liquid chromatographic separation of the globin chains of non-human hemoglobins.

High performance liquid chromatography has been applied to the separation of the globin chains of 16 non-human species which include common mammalian and avian species. The procedure uses a large-pore C4 column which has been effectively employed for the separation of human globin chains. In many cases, the gradient for human chains with trifluoroacetic acid-water-acetonitrile was satisfactory or required only moderate modification. The separations were excellent for all except dog hemoglobin. Many results substantiate prior published information about heterogeneity, amino acid composition, etc. of the individual hemoglobins. Additional data on some of these hemoglobins have also been obtained, and some previously unstudied hemoglobins have been examined.

Preparation and characterization of pentaammineruthenium-(histidine-83)azurin: thermodynamics of intramolecular electron transfer from ruthenium to copper.

The reaction between a5RuH2O2+ (a is NH3) and Pseudomonas aeruginosa azurin at pH 7, followed by oxidation, yields a5Ru(His-83)3+-azurin(Cu2+) as the major product. Spectroscopic measurements (UV-visible, CD, EPR, and resonance Raman) indicate that the native structure is maintained in the modified protein. The site of ruthenium binding (His-83) was identified by peptide mapping. The a5RuHis/Cu ratio in the modified protein, determined from the EPR spectrum, is 1:1, and the reduction potentials (vs. normal hydrogen electrode, pH 7.0, 25 degrees C) are blue copper (Cu2+/1+), 320 +/- 2 mV; a5Ru(His-83)3+/2+, 50 +/- 10 mV. From measurements of the reduction potentials at several temperatures in the 5-40 degrees C range, delta H degree for intramolecular Ru2+ ----Cu2+ electron transfer was estimated to be -12.4 kcal mol-1 (1 cal = 4.184 J). Analysis of kinetic data in light of the electron transfer exothermicity indicates that the reorganizational enthalpy of the blue copper site can be no larger than 7.1 kcal mol-1.

Speciation in the baboon and its relation to gamma-chain heterogeneity and to the response to induction of HbF by 5-azacytidine.

In the baboon (Papio species), the two nonallelic gamma-genes produce gamma-chains that differ at a minimum at residue 75, where isoleucine (I gamma-chain) or valine (V gamma) may be present. This situation obtains in baboons that are sometimes designated as Papio anubis, Papio hamadryas, and Papio papio. However, in Papio cynocephalus, although the I gamma-chains are identical with those in the above mentioned types, the V gamma-chains have the substitutions ala----gly at residue 9 and ala----val at residue 23. The V gamma-chains of P. cynocephalus are called V gamma C to distinguish them from the V gamma A-chains of P. anubis, etc. A single cynocephalus animal has been found to have only normal I gamma-chains and I gamma C-chains (that is, glycine in residue 9, valine in 23, and isoleucine in 75). When HbF is produced in response to stress with 5-azacytidine, P. anubis baboons respond with greater production than do P. cynocephalus, and hybrids fall between. Minimal data on P. hamadryas and P. papio suggest an even lower response than P. cynocephalus. As HbF increases under stress, the ratio of I gamma to V gamma-chains changes from the value in the adult or juvenile baboon toward the ratio in the newborn baboon. However, it does not attain the newborn value. The V gamma A and V gamma C-genes respond differently to stress. In hybrids, the production of V gamma A-chains exceeds that of V gamma C-chains. A controlling factor in cis apparently is present and may be responsible for the species-related extent of total HbF production. It may be concluded that the more primitive the cell in the erythroid maturation series that has been subjected to 5-azacytidine, the more active is the I gamma-gene.

Anisotropic diffusion of oxygen in slices of rat muscle.

The diffusion coefficient of oxygen (D) and the fluorescence quenching coefficient (K') of pyrenebutyric acid (PBA) were measured in sections of rat hamstring muscles. Values of D and K' at temperatures (Tc) of 20, 30, and 40 degrees C were determined and referred to the values in water. In sections cut parallel to the muscle fibers, D = DH2O (0.380 +/- 0.038), whereas in sections cut across the grain of the fibers, D = DH2O (0.985 +/- 0.039). Oxygen diffuses along the length of a muscle fiber over twice as rapidly as it diffuses in directions perpendicular to the long axis of the fiber. This suggests that fibers, myofibrils, or myofilaments offer substantial barriers to the diffusion of oxygen, whereas extracellular space and spaces around fibers or myofibrils or myofilaments offer no more resistance than water to the diffusion of oxygen. Corresponding estimates for K' were K' = K'H2O[0.14 (1 + 0.25 Tc)] and K' = K'H2O[0.21 (1 + 0.25 Tc)] for slices cut parallel to the long axis of muscle fibers and across the long axis, respectively. Standard deviations of K' were 9%.

Changes in the gamma chain heterogeneity of hemoglobin F of the baboon (Papio cynocephalus) postnatally and after partial switching to hemoglobin F production by various stimuli.

The postnatal switch from hemoglobin (Hb) F to Hb A in the baboon (Papio cynocephalus) occurs somewhat more rapidly than in humans. Minor components which are related to Hb F and Hb A are also present and show reciprocal rise and fall. The baboon produces two types of gamma chain presumably from nonallelic genes. These have either an isoleucyl (I gamma) or a valyl (V gamma) residue in position 75. As in the human case with G gamma and A gamma chains, the ratio I gamma to V gamma chains changes during the postnatal switch. Production of Hb F in the baboon may be stimulated by phenylhydrazine or more effectively by 5-azacytidine. With phenylhydrazine, the ratio of I gamma to V gamma chains in the Hb F is the same as in the traces of Hb F in the juvenile or adult baboon. However, with 5-azacytidine, at least some of the Hb F that is produced probably has been synthesized with an I gamma to V gamma ratio that is present prenatally and in the newborn baboon.

Diffusion of oxygen in slices of rat brain.

A new method for the joint determination in tissue slices of the diffusion coefficient of oxygen (D) and the fluorescence-quenching coefficient (K') of pyrenebutyric acid (PBA) is introduced. Values of D and K' in rat brain at temperatures (Tc) from 20 to 40 degrees C were determined and referred to the values in water. D = DH2O (0.72 - 0.0074 Tc) +/- 0.079 X 10(-5) cm2/s for 80-microns slices. D = DH2O (1.01 - 0.0074 Tc) +/- 0.12 X 10(-5) cm2/s for 160-microns slices. K' = K'H2O (0.72 + 0.025 Tc) +/- 0.56 X 10(-4) mmHg-1. The temperature dependence of both these parameters in tissue is different from their temperature dependence, and comparison with parameter values obtained with other methods leads us to conclude that factors affecting the diffusion of oxygen in tissue are heterogenous rather than homogenous. The variation in the different parameters, D and K', probably exceeds a twofold range.