The National Patient-Centered Clinical Research Network (PCORnet) Bariatric Study Cohort: Rationale, Methods, and Baseline Characteristics.

BACKGROUND: Although bariatric procedures are commonly performed in clinical practice, long-term data on the comparative effectiveness and safety of different procedures on sustained weight loss, comorbidities, and adverse effects are limited, especially in important patient subgroups (eg, individuals with diabetes, older patients, adolescents, and minority patients). OBJECTIVE: The objective of this study was to create a population-based cohort of patients who underwent 3 commonly performed bariatric procedures-adjustable gastric band (AGB), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG)-to examine the long-term comparative effectiveness and safety of these procedures in both adults and adolescents. METHODS: We identified adults (20 to 79 years old) and adolescents (12 to 19 years old) who underwent a primary (first observed) AGB, RYGB, or SG procedure between January 1, 2005 and September 30, 2015 from 42 health systems participating in the Clinical Data Research Networks within the National Patient-Centered Clinical Research Network (PCORnet). We extracted information on patient demographics, encounters with healthcare providers, diagnoses recorded and procedures performed during these encounters, vital signs, and laboratory test results from patients' electronic health records (EHRs). The outcomes of interest included weight change, incidence of major surgery-related adverse events, and diabetes remission and relapse, collected for up to 10 years after the initial bariatric procedure. RESULTS: A total of 65,093 adults and 777 adolescents met the eligibility criteria of the study. The adult subcohort had a mean age of 45 years and was predominantly female (79.30%, 51,619/65,093). Among adult patients with non-missing race or ethnicity information, 72.08% (41,248/57,227) were White, 21.13% (12,094/57,227) were Black, and 20.58% (13,094/63,637) were Hispanic. The average highest body mass index (BMI) recorded in the year prior to surgery was 49 kg/m2. RYGB was the most common bariatric procedure among adults (49.48%, 32,208/65,093), followed by SG (45.62%, 29,693/65,093) and AGB (4.90%, 3192/65,093). The mean age of the adolescent subcohort was 17 years and 77.5% (602/777) were female. Among adolescent patients with known race or ethnicity information, 67.3% (473/703) were White, 22.6% (159/703) were Black, and 18.0% (124/689) were Hispanic. The average highest recorded BMI in the year preceding surgery was 53 kg/m2. The majority of the adolescent patients received SG (60.4%, 469/777), followed by RYGB (30.8%, 239/777) and AGB (8.9%, 69/777). A BMI measurement (proxy for follow-up) was available in 84.31% (44,978/53,351), 68.09% (20,783/30,521), and 68.56% (7159/10,442) of the eligible adult patients at 1, 3, and 5 years of follow-up, respectively. The corresponding proportion was 82.0% (524/639), 49.9% (174/349), and 38.8% (47/121) in the adolescent subcohort. CONCLUSIONS: Our study cohort is one of the largest cohorts of patients with bariatric procedures in the United States. Patients are geographically and demographically diverse, which improves the generalizability of the research findings and allows examination of treatment effect heterogeneity. Ongoing and planned investigations will provide real-world evidence on the long-term benefits and risks of these most commonly used bariatric procedures in current clinical practice.

Highly antibiotic-resistant Acinetobacter baumannii clinical isolates are killed by the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG).

Acinetobacter baumannii is an increasingly common cause of infection in intensive-care units throughout the world, and the occurrence of multiresistant A. baumannii is increasing. The aim of this study was to determine whether a highly purified polyphenol, (-)-epigallocatechin-3-gallate (EGCG), from green tea (Camellia sinesis), had antimicrobial effects against multiresistant clinical isolates of A. baumannii. Standard microplate assays were performed to determine the MIC of EGCG for 21 clinical isolates of A. baumannii. MICs ranged from 0.078 to 0.625 mg/mL, with MIC(50) and MIC(90) of 0.312 mg/mL and 0.625 mg/mL, respectively. All of the isolates of A. baumannii tested were killed by EGCG. In time-kill assays, EGCG resulted in a 3-log reduction in CFU/mL of A. baumannii after 5 h of incubation with the polyphenol. Synergy between the commonly used topical agent 5% mafenide acetate (Sulfamylon) and EGCG was noted for one clinical isolate, and partial synergy was noted for three other isolates. These findings demonstrate that EGCG is an effective bactericidal agent against antibiotic-resistant A. baumannii clinical strains in laboratory settings. EGCG has previously been shown to be safe, and therefore may be an attractive addition for the treatment of cutaneous A. baumannii infections where high concentrations of the drug can be applied to the wound surface.

The natural history of periodontal disease in man. Risk factors for progression of attachment loss in individuals receiving no oral health care.

BACKGROUND: Few investigations have reported on risk factors for periodontal attachment loss over time in subjects with no home or professional dental care. The purpose of this report was to identify potential risk factors for progression of periodontal attachment loss among male Sri Lankan tea laborers who participated in a 20-year investigation of the natural history of periodontal disease. METHODS: Data for this report were obtained from the 154 subjects who participated in the 1970 baseline and the final 1990 examinations and included data from their interim examinations performed in 1971, 1973, 1977, 1982, and 1985. Oral health assessments included: 1) attachment levels in millimeters on mesial and mesio-buccal surfaces of all but third molar teeth; 2) plaque index (PI); 3) gingival index (GI); 4) calculus index (CI); 5) caries index (DMFS); and 6) presence or absence of teeth. Other variables included age, history of smoking, and/or use of betel nut. Statistical analyses used multivariate repeated measures analysis of variance (ANOVA). RESULTS: The final adjusted model indicated that attachment loss increased significantly with age (X2 = 74.0; df = 1), GI (X2 = 45.5; df = 1), CI (X2 = 52.7; df = 1) and follow-up time (X2 = 219.8; df = 6, P<0.0001 for all variables). CONCLUSIONS: Age, GI, CI, and time were significantly associated with mean attachment loss over 20 years. Neither PI, history of smoking, or history of betel nut use were significantly associated with attachment loss over time.

Survival of enterococci and staphylococci on hospital fabrics and plastic.

The transfer of gram-positive bacteria, particularly multiresistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), among patients is a growing concern. One critical aspect of bacterial transfer is the ability of the microorganism to survive on various common hospital surfaces. The purpose of this study was to determine the survival of 22 gram-positive bacteria (vancomycin-sensitive and -resistant enterococci and methicillin-sensitive and -resistant staphylococci) on five common hospital materials: smooth 100% cotton (clothing), 100% cotton terry (towels), 60% cotton-40% polyester blend (scrub suits and lab coats), 100% polyester (privacy drapes), and 100% polypropylene plastic (splash aprons). Swatches were inoculated with 10(4) to 10(5) CFU of a microorganism, assayed daily by placing the swatches in nutritive media, and examining for growth after 48 h. All isolates survived for at least 1 day, and some survived for more than 90 days on the various materials. Smaller inocula (10(2)) survived for shorter times but still generally for days. Antibiotic sensitivity had no consistent effect on survival. The long survival of these bacteria, including MRSA and VRE, on commonly used hospital fabrics, such as scrub suits, lab coats, and hospital privacy drapes, underscores the need for meticulous contact control procedures and careful disinfection to limit the spread of these bacteria.

Ultrafast inactivation causes inward rectification in a voltage-gated K(+) channel from Caenorhabditis elegans.

The exp-2 gene in the nematode Caenorhabditis elegans influences the shape and duration of the action potential of pharyngeal muscle cells. Several loss-of-function mutations in exp-2 lead to broadening of the action potential and to a concomitant slowing of the pumping action of the pharynx. In contrast, a gain-of-function mutation leads to narrow action potentials and shallow pumping. We cloned and functionally characterized the exp-2 gene. The exp-2 gene is homologous to genes of the family of voltage-gated K(+) channels (Kv type). The Xenopus oocyte-expressed EXP-2 channel, although structurally closely related to Kv-type channels, is functionally distinct and very similar to the human ether-à-gogo-related gene (HERG) K(+) channel. In response to depolarization, EXP-2 activates slowly and inactivates very rapidly. On repolarization, recovery from inactivation is also rapid and strongly voltage-dependent. These kinetic properties make the Kv-type EXP-2 channel an inward rectifier that resembles the structurally unrelated HERG channel. Apart from many similarities to HERG, however, the molecular mechanism of fast inactivation appears to be different. Moreover, the single-channel conductance is 5- to 10-fold larger than that of HERG and most Kv-type K(+) channels. It appears that the inward rectification mechanism by rapid inactivation has evolved independently in two distinct classes of structurally unrelated, voltage-gated K(+) channels.

Trends in the incidence of lip, oral, and pharyngeal cancer: Connecticut, 1935-94.

Using Connecticut Tumor Registry data we explored trends in age-adjusted (AARs) and age-specific (ASRs) incidence rates for lip, oral, and pharyngeal cancer over the 60-year period 1935-94. Particular attention was given to findings from the most recent series of 5-year periods that have not been previously analyzed. There was a long-term decline in lip cancer AARs by period, and ASRs generally fell over time and with successive birth cohorts. This notable decrease in rates continued through 1990-94 and with the more recent cohorts, particularly among males. Oral cancer AARs for males peaked in the early 1960s and the late 1970s while rates for pharyngeal cancer increased into the late 1970s. For each of these sites, rates began to decline in 1980-84 and have continued to fall into the first half of the 1990s. Among females AARs for oral and pharyngeal cancer increased more than threefold between 1935-39 and 1980-84; however, encouragingly, and in sharp contrast to the earlier trend, rates fell during the most recent 10-year period. ASRs for oral and pharyngeal cancer were increasing by the birth cohort of 1900 and tended to increase through the cohort of 1920 for males and the cohorts of 1920-30 for females. ASRs for subsequent cohorts have remained relatively unchanged or decreased modestly. It is doubtful that the observed trends in lip, oral and pharyngeal cancer incidence are primarily artifactual, but more likely represent secular changes in exposure to environmental risk factors.

Role of potassium channels in amyloid-induced cell death.

Basal forebrain cholinergic neurons are severely depleted early in Alzheimer's disease and appear particularly susceptible to amyloid beta-peptide (A beta) toxicity in vivo. To model this effect in vitro, a cholinergic septal cell line (SN56) was exposed to A beta. SN56 cells exhibited a tetraethylammonium (TEA)-sensitive outward K+ current with delayed rectifier characteristics. Increases of 64% (+/-19; p < 0.02) and 44% (+/-12; p < 0.02) in K+ current density were noted 6-12 and 12-18 h following the addition of A beta to SN56 cell cultures, respectively. Morphological observation and staining for cell viability showed that 25 +/- 4 and 39 +/- 4% of SN56 cells were dead after 48- and 96-h exposures to A beta, respectively. Perfusion of SN56 cells with 10-20 mM TEA blocked 71 +/- 6 to 92 +/- 2% of the outward currents, widened action potentials, elevated [Ca2+]i, and inhibited 89 +/- 14 and 68 +/- 14% of the A beta toxicity. High [K+]o, which depolarizes cell membranes and increases [Ca2+]i, also protected SN56 cells from A beta toxicity. This effect appeared specific since glucose deprivation of SN56 cells did not alter K+ current density and TEA did not protect these cells from hypoglycemic cell death. Furthermore, A beta was toxic to a dopaminergic cell line (MES23.5) that expressed a K+ current with delayed rectifier characteristics; K+ current density was not altered by A beta and MES23.5 cells were not protected by TEA from A beta toxicity. In contrast, a noncholinergic septal cell line (SN48) that shows minimal outward K+ currents was resistant to the toxicity of A beta. These data suggest that a K+ channel with delayed rectifier characteristics may play an important role in A beta-mediated toxicity for septal cholinergic cells.

Efficacy of a rise in C-reactive protein serum levels as an early indicator of sepsis in burned children.

C-Reactive protein serum levels were measured in 57 pediatric patients with 3% to 92% total body surface area burns to determine whether a defined rise in C-reactive protein serum levels could indicate sepsis earlier in burn patients. A rise in C-reactive protein serum levels was defined as an increase of at least 3 mg/dL for 2 days or 10 mg for 1 day. Increases the first 2 days after the burn or the day after surgery were excluded, since these injuries increase C-reactive protein serum levels. Patients were defined as septic when they were on systemic antibiotics and exhibited at least two of 16 specific clinical parameters. C-Reactive protein serum levels correctly predicted sepsis 82% of the time (efficiency=82%). Nonseptic patients generally did not show increased C-reactive protein serum levels (specificity=69%). When sepsis did occur, it always was preceded by increased C-reactive protein (sensitivity=100%), and the increased C-reactive protein occurred 2.3+/-0.5 days before the patient was deemed septic clinically. Hence, a defined rise in C-reactive protein serum levels can predict sepsis sooner in burned children.

Recombinant neutral endopeptidase decreases oedema in the skin of burned guinea-pigs.

Oedema, due to increased vascular leakage postburn, cases significant problems for burn patients. The purpose of this study was to determine if local application of a recombinant neutral endopeptidase (rNEP) would reduce the increased vascular permeability caused by a burn. In a guinea-pig model, a single treatment of rNEP given immediately postburn significantly decreased burn-induced plasma extravasation. This rNEP effect was dependent upon both the dosage of the peptidase and its enzymatic activity. Additional experiments were consistent with the rNEP acting partly by degrading bradykinin, a mediator of increased vascular permeability postburn. These findings suggest that further study of rNEP as a possible treatment for oedema is warranted.

Circulating levels of tumour necrosis factor, interleukin 6 and proteolytic activity in a murine model of burn and infection.

Cytokines and proteinases have both been implicated as mediators in the inflammatory response associated with trauma and sepsis. Using a burned-infected mouse model, it was previously found that mortality is proportional to the amount of proteolytic activity (PA) in the circulation. However, little is known about circulating cytokine levels in hosts that are both burned and infected. With this mouse model, both tumour necrosis factor (TNF) and interleukin 6 (IL-6) were upregulated by a burn and by an infection. Burn plus infection produced an additive effect on each cytokine, but IL-6 levels correlated better with mortality. Treating mice with the proteinase inhibitor aprotinin immediately preburn and infectious challenge significantly decreased IL-6, PA and mortality. This may be a clinically relevant model for studying mediators in burned and/or septic hosts.

Patients undergoing reconstructive surgery versus unburned children as "controls" in studies of pediatric patients with burns.

A valid control group is an essential part of any patient study. We asked whether burned children returning for reconstructive surgery could be used as "controls" in a study of seven proteolytic elements in the circulation. Functional levels of elastase, plasminogen, prekallikrein, antithrombin, alpha 2-antiplasmin, alpha 2-macroglobulin, and total proteolytic activity in 30 healthy unburned children were compared with levels in 29 patients admitted for reconstructive surgery an average of 7.9 years after burn. The two groups were not statistically different in distributions of sex and race but differed in mean age. Levels of six of the seven parameters were equal in the two groups. However, even when correction for the age difference was done between the groups, alpha 2-macroglobulin in the patients undergoing reconstructive surgery still was significantly less (p < 0.021) than in the unburned group. Therefore caution may be needed when readily available patients undergoing reconstructive surgery are used as "controls" in studies of patients with acute burns.

Molecular analysis and functional expression of the human type E neuronal Ca2+ channel alpha 1 subunit.

A human brain alpha 1 Ca2+ channel subunit was cloned and expressed in Xenopus laevis oocytes. The open reading frame, encoding 2,312 amino acids, has high homology to the marine ray doe-1, the rat E-type, and the rabbit brain BII alpha 1 subunits. The amino and carboxy termini of this human.E-type alpha 1 subunit (alpha 1E) are most similar to the rabbit BII-1 splice variant, the remainder being colinear with the BII alpha 1 with the exception of two insertions, one of 43 amino acids in the C-terminus and another of 7 amino acids, found also in the rat alpha 1E, between domains II and III. Two potential Ca2+ binding sites are predicted from its primary structure. The expression of inward Ba2+ currents reveals voltage-dependent activation and inactivation measured by the cut-open oocyte vaseline-gap technique, with kinetics that correspond to that of a high-voltage-activated neuronal Ca2+ channel, and pharmacologic properties that resemble those of some low-voltage-activated neuronal Ca2+ currents. The human alpha 1E currents are insensitive to omega-conotoxin-GVIA (1 microM), omega-agatoxin-IVA (200 nM), a synthetic funnel web spider toxin (FTX, 20 microM), and Bay-K8644 (0.5 microM); they are inhibited 20% by high concentrations of methoxyverapamil and diltiazem, 65% by 0.1% crude funnel web spider venom and 100% by Ni2+ (IC50 = 30 nM). Single-channel records show a complex activity pattern with several apparent conductance states, the largest having a conductance of 14 pS.

Biologic response modifier OK-432 pretreatment reduces mortality in burned mice infected with gram-negative bacteria.

When compared with a control group, mice pretreated with the biologic response modifier OK-432 showed increased survival when burned and infected with several strains of Pseudomonas aeruginosa and a Klebsiella pneumoniae isolate. Quantitative microbial counts in the skin, liver, and kidneys of burned mice infected with Pseudomonas aeruginosa showed that although skin counts were not different between control groups pretreated or untreated with OK-432, liver and kidney counts were reduced significantly in the group pretreated with OK-432. We speculate from these results that OK-432 pretreatment may enhance survival by enhancing host clearance of microorganisms entering the circulation from the burn wound. Making mice granulocytopenic by cyclophosphamide treatment or macrophage-deficient/dysfunctional by carrageenan treatment nullified any survival advantage given by OK-432 pretreatment. These results supported our speculation and suggested that both of these cell types were important in the mechanisms of enhanced survival afforded by OK-432 pretreatment.

Hageman factor dependent activation and its relationship to lethal Pseudomonas aeruginosa burn wound infections.

Trauma causes increases in total protease load in the circulation of the traumatized host animal or patient. This increase is due, in part, to Hageman Factor activation followed by down-line cascade system activation. Concomitant with the activation of these systems is a reduced host capacity to resist infection. Infection superimposed on a traumatized host increases the total host protease load even more by additional activation of Hageman Factor and cascade systems.

The uptake and distribution of 14-C-mescaline in different organs of developing rat.

Rats of 1,4,8,12,20, and 60 days postnatal age were injected ip with 14-C-mescaline (50 nCi/g). The levels of mescaline and its deaminated metabolite, 3,4,5-trimethoxyphenylacetic acid, were examined in the brain, liver, heart, spleen, lung, and kidney at 30, 60, 90, and 120 min. Mescaline was rapidly taken up by all the organs examined. In general, the organs of younger rats accumulated much larger amounts than those of adult animals. Brain concentrated the lowest amounts in comparison with other tissues. In the brain, the uptake was the highest in 1-day-old rats and decreased with age. The disappearance of mescaline in various organs was comparatively slower in younger animals than in 20-day or older rats. Rats immediately after birth and uptake was the highest in 1-day-old rats and decreased with age. The disappearance of mescaline in various organs was comparatively slower in younger animals than in 20-day or older rats. Rats immediately after birth and up to 20 days of age metabolized mescaline less efficiently than adults. From the data, it appears that the blood-brain barrier for mescaline develops gradually with age but is not completely impermeable in adults.