Diagnostic Yield of Endoscopic Ultrasound in Common Bile Duct Dilation: A Real Breakthrough.

BACKGROUND: Endoscopic ultrasound (EUS) is important for the evaluation of patients with common bile duct (CBD) dilation. AIMS: The purpose of this study was to evaluate the diagnostic performance of EUS for CBD dilation in patients with negative initial studies. METHODS: This was a retrospective cohort study that included patients who underwent EUS for CBD dilation (≥ 7 mm if intact anatomy or ≥ 10 mm if prior cholecystectomy) in the absence of pathology on previous ultrasonography (US), computed tomography (CT), and/or magnetic resonance cholangiopancreatography (MRCP). RESULTS: A total of 109 patients were included, among whom 41 had a positive EUS: 33 choledocholithiasis (30.3%), 6 chronic pancreatitis (5.5%), and 2 ampullary cancer (1.8%). If the EUS was negative, no pathology was found during 1-year follow-up. Older age was associated with positive EUS (79 versus 71 years, p = 0.030). Patients with jaundice, cholelithiasis, and altered liver biochemistry were 16.2 (p = 0.002), 3.1 (p = 0.024), and 2.9 (p = 0.009) times more likely to have positive EUS, respectively. A total of 53 patients had a negative MRCP (48.6%); those with biliary abdominal pain and jaundice were 15.5 (p < 0.001) and 20.0 (p = 0.007) times more likely to have positive EUS, respectively. Considering asymptomatic patients with normal liver tests, CBD diameter ≥ 10 mm in US and ≥ 11 mm in CT can predict a positive EUS (AUC 0.754, p = 0.047 and AUC 0.734, p = 0.048). CONCLUSIONS: EUS is a useful diagnostic method for patients with unexplained CBD dilation, even if negative MRCP, and especially in patients with older age, abdominal pain, jaundice, cholelithiasis, and/or altered liver biochemistry. CBD diameter in US and CT had a moderate discriminative ability in predicting positive EUS in asymptomatic patients without altered liver biochemistry.

Ultrasonographic scores for ileal Crohn's disease assessment: Better, worse or the same as contrast-enhanced ultrasound?

BACKGROUND: Intestinal ultrasound (IUS) is an increasingly used non-invasive tool to evaluate Crohn's disease (CD) activity. Recently, two IUS scores that evaluate inflammatory activity have emerged: the Simple Ultrasound Activity Score for CD (SUS-CD) and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS). We aimed to compare the accuracy of SUS-CD, IBUS-SAS and contrast-enhanced ultrasound (CEUS) in predicting inflammatory activity in the terminal ileum in ileocolonoscopy in CD patients. METHODS: Retrospective study including all consecutive CD patients submitted to IUS with CEUS directed to the terminal ileum performed by a single operator between April 2016 and March 2020. Segmental SUS-CD and IBUS-SAS were calculated. A time-intensity curve of the contrast bowel wall enhancement was created with measurement of peak intensity using CEUS. The CD endoscopic activity in ileocolonoscopy was graded by Simple Endoscopic Score for CD (SES-CD) as inactive (SES-CD < 7) or active (SES-CD ≥ 7). RESULTS: Fifty patients were included, 54.0% were female, with mean age of 34 ± 12 years, and most had isolated ileal disease (60.0%), and a nonstricturing, nonpenetrating behaviour (44.0%). Most of the patients (60.0%) had active endoscopic disease (SES-CD ≥ 7). SUS-CD and IBUS-SAS were not different between patients with active or inactive endoscopic disease (p = 0.15; 0.57, respectively), having a poor accuracy to correlate endoscopic activity (area under de curve (AUC) 0.62; 0.55, respectively). Peak intensity in CEUS was significantly different in patients with active or inactive endoscopic disease (p = 0.004), having a good accuracy to correlate endoscopic activity (AUC 0.80). CONCLUSION: Unlike CEUS, SUS-CD and IBUS-SAS were not able to accurately correlate endoscopic activity in terminal ileum in CD. Therefore, CEUS is a non-invasive emerging method that should be increasingly integrated in the ultrasonographic evaluation of CD patients.

Intrathecal drug delivery in the era of nanomedicine.

Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain barrier to enable drug delivery to the central nervous system (CNS). However, molecules that have been administered by intrathecal injection, which includes intraventricular, intracisternal, or lumbar locations, encounter new barriers within the subarachnoid space. These barriers include relatively high rates of turnover as CSF clears and potentially inadequate delivery to tissue or cellular targets. Nanomedicine could offer a solution. In contrast to the fate of freely administered drugs, nanomedicine systems can navigate the subarachnoid space to sustain delivery of therapeutic molecules, genes, and imaging agents within the CNS. Some evidence suggests that certain nanomedicine agents can reach the parenchyma following intrathecal administration. Here, we will address the preclinical and clinical use of intrathecal nanomedicine, including nanoparticles, microparticles, dendrimers, micelles, liposomes, polyplexes, and other colloidalal materials that function to alter the distribution of molecules in tissue. Our review forms a foundational understanding of drug delivery to the CSF that can be built upon to better engineer nanomedicine for intrathecal treatment of disease.

Tailoring the volatility and stability of oligopeptides.

Amino acids are essential building blocks of life, and fluorinated derivatives have gained interest in chemistry and medicine. Modern mass spectrometry has enabled the study of oligo- and polypeptides as isolated entities in the gas phase, but predominantly as singly or even multiply charged species. While laser desorption of neutral peptides into adiabatically expanding supersonic noble gas jets is possible, UV-VIS spectroscopy, electric or magnetic deflectometry as well as quantum interferometry would profit from the possibility to prepare thermally slow molecular beams. This has typically been precluded by the fragility of the peptide bond and the fact that a peptide would rather 'fry', i.e. denature and fragment than 'fly'. Here, we explore how tailored perfluoroalkyl functionalization can reduce the intermolecular binding and thus increase the volatility of peptides and compare it to previously explored methylation, acylation and amidation of peptides. We show that this strategy is essential and enables the formation of thermal beams of intact neutral tripeptides, whereas only fragments were observed for an extensively fluoroalkyl-decorated nonapeptide. © 2017 The Authors. Journal of Mass Spectrometry Published by John Wiley & Sons Ltd.

Position paper on tuberculosis screening in patients with immune mediated inflammatory diseases candidates for biological therapy.

UNLABELLED: Chronic immunosuppression is a known risk factor for tuberculosis. Our aim was to reach a consensus on screening and prevention of tuberculosis in patients with immune mediated inflammatory diseases candidates to biologic therapy. METHODS: Critical appraisal of the literature and expert opinion on immunosuppressive therapies and risk of tuberculosis. RESULTS AND CONCLUSION: The currently recommended method for screening is the tuberculin skin test and the interferon gamma assay, after exclusion of active tuberculosis. Positively screened patients should be treated for latent tuberculosis infection. Patients may start biological therapy after 1 to 2 months, as long as they are strictly adhering to and tolerating their preventive regimen.

Disinfection of meticillin-resistant Staphylococcus aureus and Staphylococcus epidermidis biofilms using a remote non-thermal gas plasma.

The effective disinfection of hospital surfaces is recognised as an important factor in preventing hospital-acquired infections. The purpose of this study was to quantify the disinfection rate of a novel gas plasma system on clinically relevant biofilms. Clinical isolates of Staphylococcus epidermidis and meticillin-resistant Staphylococcus aureus (MRSA) were grown as biofilms on glass surfaces and tested in a disinfection container remote from the plasma source. The strains used in this study were known to produce substantial quantities of biofilm and average log10 counts were 9.0 and 9.1 cfu/cm(2) for S. epidermidis and MRSA respectively. Counts were reduced by between 4 and 4.5 log10 after 1h of exposure for MRSA and S. epidermidis respectively. More prolonged treatment in the case of MRSA biofilms resulted in a 5.5 log10 reduction after 90 min. Biofilm samples were also placed in medical device packaging bags and similar rates of disinfection were observed.

Inflammatory bowel disease: a patient's and caregiver's perspective.

The purpose of this study was to conduct a survey examining the impact of inflammatory bowel disease (IBD) on patients' and their caregivers' daily activities. Questionnaires were distributed to patients registered in the APDI (Portuguese Association for IBD) database and their respective caregivers in 2007. Of 422 patient respondents, 251 had Crohn's disease (CD) and 171 had ulcerative colitis (UC), with the majority of patients being women (58.1%) and aged over 40 years (37.4%). The number of disease flares experienced by IBD patients was slightly higher for patients with CD than for patients with UC (2.64 vs. 2.34), and surgery was more often required in CD patients as compared to UC patients (42.4 vs. 7%). Sixty percent (60%) of patients reported having no problems with mobility, daily activities, or personal hygiene; however, over half of all patients experienced some pain and anxiety. Adult patients and children and adolescents respectively experienced time off work or school due to their disease but caregivers were not affected in this regard. The caregivers life (N=324) was affected by anxiety, with the major concern reported as the risk of the patient developing cancer. Both IBD patients and caregivers thought that the provision of information on new drugs and contact time with a doctor would have the biggest impact on improving care. The symptoms and complications of IBD have a considerable impact on the lives of patients and their caregivers, and several actions could be taken to improve their care.

Increased fat oxidation and regulation of metabolic genes with ultraendurance exercise.

AIM: Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. METHODS: Data were obtained from 11 competitors of a 4- to 5-day, almost continuous ultraendurance race (seven males, four females; age: 36 +/- 11 years; cycling Vo(2peak): males 57.4 +/- 5.9, females 48.1 +/- 4.0 mL kg(-1) min(-1)). Before and after the race muscle biopsies were obtained from vastus lateralis, respiratory gases were sampled during cycling at 25 and 50% peak aerobic power output, venous samples were obtained, and fat mass was estimated by bioimpedance under standardized conditions. RESULTS: After the race fat mass was decreased by 1.6 +/- 0.4 kg (11%; P < 0.01). Respiratory exchange ratio at the 25 and 50% workloads decreased (P < 0.01) from 0.83 +/- 0.06 and 0.93 +/- 0.03 before, to 0.71 +/- 0.01 and 0.85 +/- 0.02, respectively, after the race. Plasma fatty acids were 3.5 times higher (from 298 +/- 74 to 1407 +/- 118 micromol L(-1); P < 0.01). Muscle glycogen content fell 50% (from 554 +/- 28 to 270 +/- 25 nmol kg(-1) d.w.; n = 7, P < 0.01), whereas the decline in muscle triacylglycerol (from 32 +/- 5 to 22 +/- 3 mmol kg(-1) d.w.; P = 0.14) was not statistically significant. After the race, muscle mRNA content of lipoprotein lipase and glycogen synthase increased (P < 0.05) 3.9- and 1.7-fold, respectively, while forkhead homolog in rhabdomyosarcoma, pyruvate dehydrogenase kinase 4 and vascular endothelial growth factor mRNA tended (P < 0.10) to be higher, whereas muscle peroxisome proliferator-activated receptor gamma co-activator-1beta mRNA tended to be lower (P = 0.06). CONCLUSION: Very prolonged exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes.

Gas-permeable scleral contact lens therapy in ocular surface disease.

PURPOSE: To describe the therapeutic benefits of nonfenestrated gas-permeable scleral contact lenses in the management of patients with ocular surface disease. METHODS: The charts of 49 consecutive patients (76 eyes) with ocular surface disease whose management included the use of gas-permeable scleral contact lenses were reviewed. We also developed a questionnaire to assess the impact of lens wear on subjective aspects of activities of daily living. RESULTS: The mean age of the 49 patients was 44.6 years (range, 3 to 87 years); 31 patients were female and 18 were male. The most common indication for fitting of the lenses was Stevens-Johnson syndrome (54 [71%] of the 76 eyes). Other indications included ocular cicatricial pemphigoid, exposure keratitis, toxic epidermal necrolysis, postherpetic keratitis, congenital deficiency of meibomian glands, superior limbal keratoconjunctivitis, Sjögren syndrome, and inflammatory corneal degeneration. The mean follow-up was 33.6 months (range, 2 to 144 months). Improvement in best-corrected visual acuity (defined as a gain of 2 or more Snellen lines) was observed in 40 (53%) of the eyes. In eight (53%) of the 15 eyes with active corneal epithelial defects at the time of lens fitting, the defects healed, whereas in the remaining seven eyes the corneal epithelial defects remained unchanged. Forty-five (92%) of the 49 patients reported improvement in their quality of life as a result of reduction of photophobia and discomfort. The mean wearing time of the gas-permeable scleral contact lenses was 13.7 hours per day (range, 4 to 18 hours). Many patients had preparatory surgical procedures before lens fitting (for example, punctal occlusion or mucous membrane grafting), and some had visual rehabilitation surgical procedures (for example, keratoplasty and/or cataract surgery) after lens fitting. CONCLUSIONS: Gas-permeable scleral contact lens wear provides an additional effective strategy in the surface management and visual rehabilitation of patients with severe ocular surface disease.

Treatment of persistent corneal epithelial defect with extended wear of a fluid-ventilated gas-permeable scleral contact lens.

PURPOSE: To report treatment of persistent corneal epithelial defects unresponsive to other therapies by extended wear of a fluid-ventilated gas-permeable scleral contact lens. METHODS: In this retrospective study, 14 eyes of 13 consecutive patients referred for the treatment of persistent corneal epithelial defects that failed to heal with conventional therapies or developed epithelial defects after penetrating keratoplasty for persistent corneal epithelial defects were fitted with an extended-wear gas-permeable scleral lens. These included seven eyes of six patients with Stevens-Johnson syndrome and seven eyes of seven patients who did not have Stevens-Johnson syndrome. Twelve eyes had undergone recent penetrating keratoplasty. All 14 eyes were fitted with a gas-permeable scleral contact lens designed to avoid the intrusion of air bubbles under its optic. An antibiotic and corticosteroid were added to the lens fluid reservoir or instilled before each lens insertion in 12 of 14 eyes. The lenses were worn continuously except for brief periods of removal for purposes of cleaning, replacement of the lens fluid reservoir, and examination and photography of the cornea. RESULTS: Five of the seven persistent corneal epithelial defects associated with Stevens-Johnson syndrome healed. The persistent corneal epithelial defects of four of these eyes re-epithelialized within 7 days, and a fifth healed in 27 days of gas-permeable scleral lens extended wear. A sixth persistent corneal epithelial defect that failed to heal initially re-epithelialized after a subsequent penetrating keratoplasty and gas-permeable scleral lens extended wear. The seventh eye healed after 3 days of gas-permeable scleral lens extended wear, but the persistent corneal epithelial defect subsequently recurred. Three of seven non-Stevens-Johnson syndrome persistent corneal epithelial defects re-epithelialized within 36 hours, 6 days, and 36 days, respectively. Of the six (six of 14) persistent corneal epithelial defects that failed to heal with a gas-permeable scleral lens extended wear, one subsequently healed after multiple amniotic membrane grafts. Microbial keratitis occurred in four eyes (four of 14) and graft failure in one eye, all of which required repeat penetrating keratoplasty. CONCLUSION: Extended wear of an appropriately designed gas-permeable scleral contact lens was effective in promoting the healing of persistent corneal epithelial defects in some eyes that failed to heal after other therapeutic measures. Re-epithelialization appears to be aided by a combination of oxygenation, moisture, and protection of the fragile epithelium afforded by the scleral lens. However, microbial keratitis represents a significant risk.

31P-NMR evaluation of postischemia renal ATP and pH levels after ATP-MgCl2 treatment in rabbits.

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy was used to measure adenosine triphosphate (ATP) concentration and pH in vivo in rabbits subjected to a 40-minute period of unilateral renal ischemia to determine the effect of infusing ATP-magnesium chloride (MgCl2, 100 mumol/kg) versus saline at the initiation of reperfusion. Data were compared initially by analysis of variance and then analyzed further using a general linear model with covariate adjustment. ATP-MgCl2-treated animals did not have higher ATP levels during recovery but did have significantly higher renal blood flow (p less than 0.05), a significantly decreased rate of recovery from acidosis (p less than 0.05), and significantly higher urinary output (p less than 0.01) than saline-treated animals during the recovery period. Therefore, treatment with ATP-MgCl2 improves postischemic functional parameters in this model of moderate injury without functioning as a direct source of ATP or its precursors. These data add support to the emerging concept that intracellular acidosis protects cells from reperfusion injury.

No-suture aphakic epikeratoplasty.

BACKGROUND: Use of sutures with aphakic epikeratoplasty is time-consuming during surgery and can create significant hazards for the patient. Thus, a surgical technique for aphakic epikeratoplasty without sutures was developed. METHODS: The conventional procedure was modified to use an oversized lenticule tucked evenly in an expanded lamellar pocket with no anchoring sutures. The technique was performed on one eye of 27 consecutive patients over a 9-month period. RESULTS: After a mean follow up of 14 months, results showed refractive and visual parameters comparable to a sutured technique. A 100% success rate at surgery was obtained using the oversized 9-millimeter lenticule. Five eyes (19.2%) developed a partial lenticule edge dislocation postoperatively. Three of the edge dislocations were reposited at the slit lamp without suturing. One lenticule, manufactured undersize, required primary suturing, leaving 24 of 26 (92.3%) patients healed without sutures. Postoperative spectacle-corrected acuity for the group either improved by one or more Snellen lines or remained unchanged. Two patients had reduced vision: one due to unrelated retinal changes and one due to vernal catarhh resulting in a persistent epithelial defect with subsequent epithelial haze. CONCLUSIONS: A sutureless technique can accomplish visual rehabilitation comparable to the conventional procedure. While the technique is not without complication, significant benefits to the patient include reduced morbidity, eliminating hazards of postoperative suture management, and a simplified surgical procedure.

Epikeratoplasty for keratoglobus associated with blue sclera.

Patients with keratoglobus and blue sclera as part of a generalized connective tissue disorder are at a high risk of developing corneal perforations either spontaneously or after mild trauma. Six patients (6 eyes) between the ages of 2 and 16 years of age (mean, 7.5 years) with keratoglobus, blue sclera, hypermobile joints, and consanguineous parents were treated by epikeratoplasty, using commercially prepared 12.5-mm lenticules. Surgery was performed for tectonic support and/or visual improvement and was successful in five of six patients with a follow-up period of 11 to 27 months (mean, 21 months). One lenticule was removed because the epithelium did not heal. Peripheral interface opacities occurred in three patients.

[Endoscopic sclerosis for hemorrhage caused by peptic ulcer: a real advance]. / Esclerose endoscópica na hemorragia por úlcera péptica: um avanço real.

The new methods of endoscopic hemostasis for bleeding gastric or duodenal ulcers are discussed. These techniques are increasingly important in patients with high risk for surgery. Due to its low cost, technical simplicity and a success rate similar to the other methods, endoscopic sclerosis is probably the first choice therapy for these conditions.

Corneal stromal wound healing in rabbits after 193-nm excimer laser surface ablation.

An argon fluoride excimer laser (193 nm) with a moving slit delivery system was used to perform anterior myopic keratomileusis in both eyes of 24 New Zealand white rabbits. Rabbits were killed immediately after ablation and at intervals up to 100 days. By slit-lamp microscopy, four rabbits at day 100 exhibited four clear corneas and four corneas had central, spotty, subepithelial haze. Light and electron microscopy documented corneal healing. In the early stages a transient acellular zone in the anterior stroma appeared over a period of three weeks, followed by an increased number of fibrocytes. In the corneas with opacification, focal areas of 20-microns-thick subepithelial scarring were present. An unexpected finding was transient damage to posterior stromal keratocytes and endothelial cells. The endothelium produced a layer of granular material that migrated anteriorly across Descemet's membrane. Immunochemistry at day 6 showed a marked staining for collagen IV, proteoglycans, fibronectin, and laminin.

Immunocytochemical localization of vasoactive intestinal polypeptide (VIP) in the brain of the little brown bat (Myotis lucifugus).

Vasoactive intestinal polypeptide (VIP)-like immunoreactivity has been examined in the brain of the little brown bat, Myotis lucifugus, using light microscopic immunocytochemistry and the indirect antibody enzyme method of Sternberger. Animals were sacrificed at three different and discrete levels of physiological activity: euthermic, hypothermic and hibernating. The density and distribution of immunoreactive neurons and fibres was compared in the three animal groups with the aid of a computerized image analysis system. Our results were compared with those of previous studies in laboratory species such as the rat and cat. Our study has demonstrated marked changes in the density of VIP-immunoreactive fibres and plexuses in the anterior hypothalamic area which correspond to the physiological state of the animal. In addition we have demonstrated the presence of VIP immunoreactive perikarya in a number of previously unreported locations. These include the paraventricular and periventricular hypothalamic nuclei, the linear raphe nucleus, nucleus interfascicularis, and in neurons embedded in the fibres of the dorsal tegmental decussation.

VIP-like immunoreactivity in the anterior hypothalamic area of a hibernating bat varies with physiological state.

Vasoactive intestinal polypeptide (VIP)-like immunoreactivity in the anterior hypothalamic area (AHA) was studied in 15 bats which are seasonal hibernators, using the unlabeled antibody enzyme method of Sternberger. Our results showed that the density of immunoreactive fibers and terminal plexuses in the AHA was greatest in euthermic animals and decreased dramatically when body temperature and cardiac rate were depressed and animals entered hibernation.

Distribution of somatostatinlike immunoreactivity in the brain of the little brown bat (Myotis lucifugus).

The distribution of somatostatinlike immunoreactive (SLI) perikarya, axons, and terminals was mapped in subcortical areas of the brain of the little brown bat, Myotis lucifugus, using light microscopic immunocytochemistry. A preponderance of immunoreactivity was localized in reticular, limbic, and hypothalamic areas including: 1) in the forebrain: the bed nucleus of the stria terminalis; lateral preoptic, dorsal, anterior, lateral and posterior hypothalamic areas; amygdaloid, periventricular, arcuate, supraoptic, suprachiasmatic, ventromedial, dorsomedial, paraventricular, lateral and medial mammillary, and lateral septal nuclei; the nucleus of the diagonal band of Broca and nucleus accumbens septi; 2) in the midbrain: the periaqueductal gray, interpeduncular, dorsal and ventral tegmental, pretectal, and Edinger-Westphal nuclei; and 3) in the hindbrain: the superior central and parabrachial nuclei, nucleus incertus, locus coeruleus, and nucleus reticularis gigantocellularis. Other areas containing SLI included the striatum (caudate nucleus and putamen), zona incerta, infundibulum, supramammillary and premammillary nuclei, medial and dorsal lateral geniculate nuclei, entopeduncular nucleus, lateral habenular nucleus, central medial thalamic nucleus, central tegmental field, linear and dorsal raphe nuclei, nucleus of Darkschewitsch, superior and inferior colliculi, nucleus ruber, substantia nigra, mesencephalic nucleus of V, inferior olivary nucleus, inferior central nucleus, nucleus prepositus, and deep cerebellar nuclei. While these results were similar in some respects to those previously reported in rodents, they also provided interesting contrasts.

Risk factors for intraoperative complications in 1000 extracapsular cataract cases.

A prospective study of the risk factors in extracapsular surgery was carried out between October 1984 and April 1986. One thousand extracapsular cataract extractions were performed by seven physicians. Decreasing pupil size was the only statistically significant risk factor for vitreous loss (P = 0.0002). Zonular breaks occurred more commonly with pseudoexfoliation syndrome (PX) (P less than 0.0001), with decreasing pupil size (P less than 0.0001), and with one surgeon who used the Simcoe aspirating needle (Storz) exclusively (P = 0.0001). It is acknowledged that it is very difficult to standardize what constitutes a small zonular break; hence, the increase in zonular breaks recorded by this surgeon may have been due only to his using less stringent criteria than the others. Capsule breaks had no significant risk factors at the 0.01 level. High myopia, advanced cataract, glaucoma, advanced age, and diabetes mellitus were not found to be risk factors for vitreous loss, zonular breaks, or capsular breaks.