Predictors of hospital transfer and associated risks of mortality in acute pancreatitis

BackgroundThere is limited research in prognosticators of hospital transfer in acute pancreatitis (AP). Hence, we sought to determine the predictors of hospital transfer from small/medium-sized hospitals and outcomes following transfer to large acute-care hospitals.MethodsUsing the 2010–2013 Nationwide Inpatient Sample (NIS), patients ≥18 years of age with a primary diagnosis of AP were identified. Hospital size was classified using standard NIS Definitions. Multivariable analyses were performed for predictors of “transfer-out” from small/medium-sized hospitals and mortality in large acute-care hospitals.ResultsAmong 381,818 patients admitted with AP to small/medium-sized hospitals, 13,947 (4%) were transferred out to another acute-care hospital. Multivariable analysis revealed that older patients (OR = 1.04; 95%CI 1.03–1.06), men (OR = 1.15; 95%CI 1.06–1.24), lower income quartiles (OR = 1.54; 95%CI 1.35–1.76), admission to a non-teaching hospital (OR = 3.38; 95%CI 3.00–3.80), gallstone pancreatitis (OR = 3.32; 95%CI 2.90–3.79), pancreatic surgery (OR = 3.14; 95%CI 1.76–5.58), and severe AP (OR = 3.07; 95%CI 2.78–3.38) were predictors of “transfer-out”. ERCP (OR = 0.53; 95%CI 0.43–0.66) and cholecystectomy (OR = 0.14; 95%CI 0.12–0.18) were associated with decreased odds of “transfer-out”.Among 507,619 patients admitted with AP to large hospitals, 31,058 (6.1%) were “transferred-in” from other hospitals. The mortality rate for patients “transferred-in” was higher than those directly admitted (2.54% vs. 0.91%, p < 0.001). Multivariable analysis revealed that being “transferred-in” from other hospitals was an independent predictor of mortality (OR = 1.47; 95% CI 1.22–1.77).ConclusionsPatients with AP transferred into large acute-care hospitals had a higher mortality than those directly admitted likely secondary to more severe disease. Early implementation of published clinical guidelines, triage, and prompt transfer of high-risk patients may potentially offset these negative outcomes.     

Sinus of valsalva aneurysms involving both coronary ostia

Sinus of Valsalva aneurysms are a rare cause of angina or myocardial infarction. We describe a patient with unstable angina and massive unruptured aneurysms of both coronary sinuses causing severe distortion of both coronary ostia, to our knowledge not previously reported. This unusual patient underwent aortic valve replacement, ascending aortic repair, and coronary artery bypass. At 11-year follow-up, she had developed severe mitral stenosis and prosthetic aortic valve stenosis. Review of the literature reveals 30 reported cases of Sinus of Valsalva aneurysm complicated by coronary insufficiency or infarction, involving either the left (20 cases) or the right coronary sinus (10 cases). We emphasize the poor outcome of these patients, especially if treated conservatively. © 1993 Wiley-Liss, Inc.     

Initial results of a new procedure for treatment of malignant obstruction of the left colon

PURPOSE: This study was undertaken to analyze the results obtained in 38 unselected patients using a new and original procedure for treatment of malignant obstructions of the left colon. METHOD: This procedure involves three phases: 1) resolution of the obstruction by means of a stem placed at the site of the tumor; 2) recovery of the general state of the patient, study of the extent of disease, and mechanical preparation of the colon; 3) regulated and final surgery (if this is not suitable, the stent may be used as definitive palliative treatment). RESULTS: In 35 patients (92 percent), the obstruction was resolved with the stent. In 22 patients the three phases were completed, and in 13 patients the stent constituted definitive palliative treatment. Only one patient (2.6 percent) died after resection of the tumor. CONCLUSION: This procedure offers a new, safe, and efficacious option for treatment of neoplastic colorectal obstructions.     

Specific Recognition of Plasma Membranes by Embryonic Cells

Methods have been developed for preparation of plasma membrane fractions from embryonic neural retina and cerebellum. These membrane fractions are specifically bound by intact cells of the original tissue (homotypic binding) and not by cells from the other tissue (heterotypic binding). Aggregation of neural retina cells and cerebellar cells is prevented by addition of homotypic membranes but not by heterotypic membranes. We conclude that, under our assay conditions, these embryonic cells specifically recognize homotypic membranes, and that the specificity of recognition is the same as in the initial step in the process of cellular aggregation.     

Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure

Chronic nicotine exposure (CNE) alters synaptic transmission in the ventral tegmental area (VTA) in a manner that enhances dopaminergic signaling and promotes nicotine use. The present experiments identify a correlation between enhanced production of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) and diminished release of the inhibitory neurotransmitter GABA in the VTA following CNE. To study the functional role of on-demand 2-AG signaling in GABAergic synapses, we used 1,2,3-triazole urea compounds to selectively inhibit 2-AG biosynthesis by diacylglycerol lipase (DAGL). The potency and selectivity of these inhibitors were established in rats in vitro (rat brain proteome), ex vivo (brain slices), and in vivo (intracerebroventricular administration) using activity-based protein profiling and targeted metabolomics analyses. Inhibition of DAGL (2-AG biosynthesis) rescues nicotine-induced VTA GABA signaling following CNE. Conversely, enhancement of 2-AG signaling in naïve rats by inhibiting 2-AG degradation recapitulates the loss of nicotine-induced GABA signaling evident following CNE. DAGL inhibition reduces nicotine self-administration without disrupting operant responding for a nondrug reinforcer or motor activity. Collectively, these findings provide a detailed characterization of selective inhibitors of rat brain DAGL and demonstrate that excessive 2-AG signaling contributes to a loss of inhibitory GABAergic constraint of VTA excitability following CNE.The mesocorticolimbic dopamine (DA) system provides a critical link between the brain regions that process cognitive information and those controlling motor behavior. Precise control of these ventral tegmental area (VTA) projections facilitates seeking rewarding stimuli, retreating from aversive stimuli, constraint of motivational state, and behavioral flexibility necessary for survival. GABAergic signaling provides robust inhibition that gates VTA DA cell excitability (1, 2), and loss of this inhibition leads to pathological dysregulation of mesocorticolimbic circuitry (3, 4).Endocannabinoids (eCBs) regulate DAergic activity through retrograde signaling from DA cell bodies onto presynaptic cannabinoid type 1 (CB₁) receptors expressed on both inhibitory and excitatory inputs. Although both 2-arachidonoylglycerol (2-AG) and anandamide (AEA) function as endogenous CB₁ agonists in the brain (5–7), these lipids exhibit distinct pharmacological profiles in vivo (8, 9) and mediate differential behavioral effects (10, 11). Endocannabinoids are produced and degraded on-demand, and the primary enzymes responsible for eCB degradation have been well-characterized using selective pharmacological tools that inactivate monoacylglycerol lipase (MAGL) or fatty acid amide hydrolase (FAAH) (11–13). However, a complete evaluation of the influence of eCB signaling in the brain has been hampered by the lack of appropriate corresponding tools for selectively inactivating on-demand eCB biosynthesis.Substantial evidence implicates eCB signaling in the etiology of nicotine addiction, and recent work demonstrates that chronic nicotine exposure (CNE) selectively enhances nicotine-induced increases in VTA 2-AG formation (14). The present study investigated the possible contribution of this effect to aberrant VTA DA cell excitation present following CNE (15). We find that sensitized nicotine-induced 2-AG release (14) strongly correlates with a loss of nicotine-induced GABA release, which may contribute to impaired inhibitory constraint of VTA DA cell excitation following CNE. To test this hypothesis, we characterized a series of selective inhibitors of 2-AG biosynthesis by diacylglycerol lipase α and β (DAGLα and DAGLβ; hereafter referred to as DAGL) (16–18) and 2-AG degradation by α/β-hydrolase domain 6 (ABHD6) and MAGL (11, 12, 19), and used these compounds to investigate the functional impact of enhanced 2-AG recruitment on GABAergic signaling at VTA synapses and nicotine self-administration.     

Safety and immunogenicity of a fully liquid vaccine containing five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus influenzae type b conjugate vaccines administered at two, four, six and 18 months of age

OBJECTIVE: The safety, immunogenicity and lot consistency of a fully liquid, five-component acellular pertussis combination vaccine, comprised of diphteria, tetanus and acellular pertussis, inactivated polio vaccine, Haemophilus influenzae type b (DTaP-IPV-Hib [Pediacel, sanofi pasteur, Canada]) were assessed and compared with that of Hib vaccine reconstituted with the five-component acellular pertussis combination vaccine (DTaP-IPV//Hib, Pentacel [sanofi pasteur, Canada]). METHODS: Infants were recruited at vaccine study centres in Montreal, Quebec; Simon Fraser Health Region, British Columbia, and southern Alberta after the protocol had been approved by the relevant institutional ethics committees. Written informed consent was obtained from the parents or guardians of all subjects. At two months of age, the infants were randomly assigned to receive one of three consecutive production lots of DTaP-IPV-Hib by intramuscular injection. Reactions to vaccinations were assessed by parental observation and through telephone interviews conducted by study nurses. Blood samples were obtained at two, six, seven, 18 and 19 months of age for measurement of antibodies to vaccine antigens. RESULTS: Most injection site and systemic reactions were mild or moderate, and of brief duration. All infants were protected against tetanus, diphtheria and all three polio serotypes after both primary and booster vaccinations. Antibody responses to pertussis antigens were similar to those observed in Swedish infants, in whom the five-component vaccine was shown to be 85% effective. Proportions of infants with antipolyribosylribitol phosphate antibody of 0.15 mug/mL or greater and 1.0 mug/mL or greater, were 97.9% and 88.9%, respectively, following primary immunization, and 100% and 99% following booster vaccination. Safety and immunogenicity results with both reconstituted and fully liquid combination vaccines were comparable. CONCLUSIONS: The fully liquid combination vaccine was comparable in terms of safety and immunogenicity with the reconstituted combination vaccine.     

Interest of home blood pressure measurements (HBPM) to establish degree of hypertensive control

Aims: To establish the validity and clinical value of home blood pressure measurements (HBPM) in the treatment follow-up of patients with essential hypertension to rule out or to confirm poor control of blood pressure obtained in the doctor's office with a mercury sphygmomanometer. Material and methods: Observational, cross-sectional study was carried out to validate HBPM in treated hypertensive patients poorly controlled by office-based casual blood pressure measurements. Measurements were made on 2 consecutive days with six readings taken per day. To do this, 2 × 2 tables were drawn up to validate the HBPM using ABPM as the reference method. Sensitivity (S), specificity (Sp), positive probability quotient (+PQ) and negative probability quotient (-PQ) were calculated. The study population (n = 149) was selected by consecutive sampling of the hypertensive patients seen in the Vallada Health Centre. Only 124 patients could be evaluated. Results: Values obtained with HBPM were: S 97.3% (95% CI 90.4-99.7%), Sp 62.7% (48.1-75.9%), +PQ 2.61 (1.82-3.73) and -PQ 0.04 (0.01-0.71). Conclusions: Home monitoring of blood pressure is a useful alternative to ABPM to rule out office-based poor control of hypertensive patients, but not to confirm it.     

Dissolution of cholesterol ductal stones in the biliary tree with medium-chain glycerides

In vitro andin vivo experiments were carried out with medium-chain glycerides.In vitro, cholesterol gallstones were rapidly dissolved by medium-chain glycerides; control experiments with saline solution failed to modify the size of the stones.In vivo, medium-chain glycerides were instilled through an, intraductal tube in 12 patients with retained bile duct stones. Perfusions lasted 2–10 days. After perfusion, stones disappeared in six cases, were reduced in size in one case, and remained unchanged in five cases. In five cases, nausea, vomiting, diarrhea, or pain were observed. Medium-chain glyceride infusion rapidly dissolves cholesterol gallstones, but is commonly associated with mild to servre side effects.