bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Barrett’s Esophagus
Authors: Younes Ziad , Duncan Mark D , Harmon John W
Published: May 2016

There have been major recent advances in the understanding of the
pathogenesis and epidemiology of Barrett’s esophagus and adenocarcinoma
of the esophagus. The advent of potent acid suppression
with proton pump inhibitors and safe, minimally invasive antireflux
procedures has made alleviating symptoms and eliminating peptic
complications achievable goals for the vast majority of patients. Endoscopic
surveillance of Barrett’s esophagus is considered the standard
of care and is widely used in clinical practice. Neither medical
nor surgical antireflux procedures, however, result in the regression
of Barrett’s esophagus in any consistent manner. Thermal and
chemical endoscopic ablation techniques show promise in both the
management of high grade dysplasia and the reversal of Barrett’s
esophagus, but these techniques are still of unproven benefit, and
can be costly and risky. Therefore, prospective and controlled studies
with long term follow‐up are needed before incorporating ablative
techniques into routine clinical practice. Management of high
grade dysplasia remains controversial. Alternative management
strategies include surveillance, resection or ablation, tailored to the
individual patient and the available expertise. Targets for future research
include defining appropriate surveillance intervals; finding
biological markers that identify patients at higher risk of progressing
to cancer; defining the cancer risk and the appropriate management
of patients with short segment Barrett’s esophagus; understanding
the natural history of dysplasia and comparing alternatives for the
management of high grade dysplasia; and studying whether surgical
management can delay or prevent the progression to dysplasia and
adenocarcinoma.
Update on Peripheral Arterial Vasodilation, Ascites and Hepatorenal Syndrome in Cirrhosis
Authors: Knotek Mladen , Rogachev Boris , Schrier Robert W
Published: May 2016

In
cirrhosis of the liver, according to the peripheral arterial vasodilation
hypothesis, relative underfilling of the arterial tree triggers a
neurohumoral response (activation of renin‐angiotensinaldosterone
system, sympathetic nervous system, nonosmotic release
of vasopressin) aimed at restoring circulatory integrity by
promoting renal sodium and water retention. Evidence has accumulated
for a major role of increased vascular production of nitric
oxide as the primary cause of arterial vasodilation in cirrhosis. Ascites
is a common complication in cirrhosis. Treatment of ascites
consists of a low salt diet with diuretics, and paracentesis together
with plasma volume expanders in diuretic‐resistant patients. Progression
of cirrhosis may result in hepatorenal syndrome, a state of
functional renal failure that carries an ominous prognosis. Orthotopic
liver transplantation has remained the only curative treatment
for patients with advanced liver disease; other modalities
such as transjugular intrahepatic portosystemic shunt or vasopressin
analogues may serve as a bridge to transplantation. Another
complication of decompensated cirrhosis is spontaneous
bacterial peritonitis, the incidence of which can be reduced by primary
or secondary antibiotic prophylaxis by using orally active antibiotics.
A Canadian Isolate of Hepatitis D (delta) Virus
Authors: Poisson Véronique , Ménard Daniel B , Frost Éric , Perreault Jean-Pierre
Published: May 2016

HepatitisD(delta) virus (HDV) is an infectious agent that propagates in hepatocytes only in the presence of hepatitis B virus, causing fulminant or chronic hepatitis with liver cirrhosis. HDV is a 36 nm particle that includes a circular RNA genome of 1.7 kilobases with an extensive internal complementary that allows it to fold into a rod-like structure. The relationships among genotypes, sequence variability, geographical distribution and disease severity of HDV remain unknown. Consequently, in the present study, the complete nucleotide sequence of anHDVisolated from a Canadian patient was determined. The viral RNA from serum was amplified using reverse transcription coupled to polymerase chain reaction amplification. The resulting complementary DNA was cloned and sequenced. Sequence analysis revealed that this new isolate contained 1672 nucleotides corresponding to genotype 1, which has a worldwide distribution. Sequencing of four independent clones revealed 17 substitutions, corresponding to an overall sequence variability of 1%. Surprisingly, seven mutations were found in the 48-nucleotide region located between the two highly conserved self-catalytic motifs. This is the first demonstration that many substitutions are identified in this region of HDV, and prompts the present authors to define it as a hypervariable region.
Long Term Follow-Up of Patients with Chronic Hepatitis C Treated with Alpha Interferon
Authors: Collier Jane D , Adams Paul A , Feinman Victor , Ghent Cameron , Witt-Sullivan Helga , Minuk Gerald , Krajden Mel , Heathcote Jenny
Published: May 2016

Interferon alpha (IFN) treatment for chronic hepatitis C induces a sustained biochemical and virological response at six months after completing 24 weeks of therapy in approximately 10% of patients. The long term durability of this ‘sustained’ response is still controversial. The aim of this multicentre study was to assess the long term virological response in patients considered to have achieved a sustained biochemical response six months after completing IFN treatment. The majority (36 of 41) of the sustained responders identified had been treated for six months with IFN therapy. Twenty-nine of the 41 patients (70%) had undetectable hepatitis C virus (HCV) RNA after a mean follow-up of 38 months after cessation of treatment (range six to 92 months). All but one of those 29 individuals had normal serum alanine aminotransferase (ALT) levels. Of the 16 patients (out of 41) who had been tested for HCV RNA six months after treatment, HCV RNA remained undetectable in 14 (88%) at final follow-up. Serum ALT values in the 11 of 12 patients whose HCV RNA was positive at final follow-up were lower than pretreatment values, and in six cases were within the normal range. The long term sustained virological response in those considered a ‘sustained responder’ six months after receiving only six months of IFN is high. Measurement of ALT is an unreliable marker of sustained response to therapy.
Primary Gastric Lymphoma of MALT: Considerations of Pathogenesis, Diagnosis and Therapy
Authors: Fischbach Wolfgang
Published: May 2016

Primary gastric
lymphoma of mucosa‐associated lymphoid tissue (MALT) is a distinct
entity with its own histological classification. Epidemiological,
histomorphological, molecular biological and experimental
data clearly underline that infection of the gastric mucosa by Helicobacter
pylori plays an important role in both the development
and progression of MALT lymphoma. Considering the histological
grade of malignancy and dissemination (stage) of the disease as
decisive prognostic factors, and therapeutic determinants, endoscopic
bioptical diagnosis and endoscopic ultrasound are of particular
importance. In cases of localized (stage 1), low grade
lymphoma, eradication of H pylori offers a promising and fascinating
therapeutic option. Surgical resection, radiotherapy or chemotherapy,
and their combination, have proven to be effective treatment
modalities. There is a need to clarify whether operative or
conservative therapeutic strategies should be favoured in the future.
Maintenance Therapy in Crohn's Disease
Authors: Steinhart Hillary
Published: May 2016

Symptoms of active
Crohn’s disease may respond to one or more of a number of
classes of drug therapies. These include systemic glucocorticoids,
budesonide, sulphasalazine, mesalazine (5-aminosalicylates), immunosuppressive
agents and antibiotics. More recently, a chimeric
mouse-human antibody to tumour necrosis factor
(infliximab) has been shown to induce clinical remission and endoscopic
improvement in patients with moderately active Crohn’s
disease refractory to other therapies. Despite this wide range of existing
therapies and the potential of emerging biological therapies,
recurrent Crohn’s disease continues to be a major impediment to
the fulfilment of a normal lifestyle and optimal quality of life for
patients with Crohn’s disease. Many drugs known to be effective
for the treatment of active disease have been tried as maintenance
therapy to prevent disease relapse or recurrence following medical
or surgical therapy. The available evidence suggests that most of
these drugs are not as useful in maintaining remission as they are in
inducing it. Systemic glucocorticoids, budesonide, mesalazine
(5-aminosalicylates), sulphasalazine and antibiotics are all associated
with either marginal therapeutic gain in the setting of
maintenance therapy or unacceptable long term toxicity. The
immunosuppressive agents azathioprine, 6-mercaptopurine and
methotrexate have been shown to have a beneficial effect in maintaining
remission and may be helpful as steroid-sparing agents.
Repeated infusions of antitumour necrosis factor antibody maintain
the improvements observed after one or two initial infusions.
The relative long term safety, efficacy and cost
effectiveness of the various choices of maintenance therapy remain
to be determined.
Intensive Care Management of Patients with Acute Liver Failure with Emphasis on Systemic Hemodynamic Instability and Cerebral Edema: A Critical Appraisal of Pathophysiology
Authors: Larsen Fin Stolze , Hansen Bent Adel , Blei Andres T
Published: May 2016

Acute liver failure (ALF) is a devastating disease
leading to multiorgan dysfunction. The most dramatic impact of
ALF is on the brain, as hepatic encephalopathy and intracranial
hypertension (IH) develop. IH is associated with systemic hemodynamic
instability, alterations in the regulation of cerebral blood
flow and the development of cerebral edema. This review focuses
on the pathophysiology of IH with special emphasis on cerebral
blood flow and the development of cerebral edema. Based on these
considerations, both traditional and new treatments for the management
of IH in the future are discussed.
Clinical Experience with Artificial Liver Support Systems
Authors: Ting Paul P , Demetriou Achilles A
Published: May 2016

Fulminant hepatic failure is a devastating disease that,
despite recent therapeutic advances, continues to be associated
with high morbidity and mortality. Orthotopic liver transplantation
has emerged as the sole modality of treatment that significantly
improves survival. However, the critical shortage of donors precludes
timely transplantation for all patients. Consequently, almost
half of all patients with fulminant hepatic failure die before a graft
becomes available. This has generated interest in developing a system
that would support patients until either native liver regeneration
occurs or an optimal donor liver can be found. Investigators
have used biological, artificial and bioartificial techniques in an attempt
to improve survival in liver failure. This article reviews the
history, the current state of the art and future directions of artificial
liver support.
Steroid-Dependent Crohn’s Disease
Authors: Sandborn William J
Published: May 2016

Placebo controlled trials have demonstrated that a tapering course of corticosteroids is an effective therapy for active Crohn’s disease. A populationbased study of 109 patients with Crohn’s disease undergoing their first course of corticosteroids showed that, at the end of one year, 44% of patients were steroid responsive, 36% were steroid dependent and 20% were steroid refractory. Side effects occur frequently during a four-month tapering course of corticosteroids, including moon face, acne, infection, ecchymoses, hypertension, hirsutism, petechial bleeding and striae. More serious side effects occur with long term use, including hypertension, diabetes, infection, osteonecrosis, osteoporosis, myopathy, cataracts, glaucoma and psychosis. Low dose corticosteroids, alternate-day corticosteroids and mesalamine (5-aminosalicylate) are not effective steroid-sparing agents in patients with Crohn’s disease. Controlled ileal release budesonide, 6 mg/day, is an effective steroid-sparing agent, but it does result in some decrease in adrenal function. Azathioprine, 6-mercaptopurine and methotrexate are all effective steroidsparing agents, as is the humanized, anti-tumour necrosis factor monoclonal antibody, CDP571. A preliminary, uncontrolled study has suggested that the mouse/human chimeric monoclonal antibody infliximab may also be steroid sparing. Surgical resection is an effective strategy to reduce steroid use in the short to intermediate term, but postoperative reoccurrence of Crohn’s disease occurs frequently. Given the morbidity associated with prolonged corticosteroid use, medical and surgical treatment strategies to reduce steroid use should be employed routinely.
New Imaging Techniques in the Evaluation of Gastrointestinal Diseases
Authors: Tafazoli Faranak , Taylor Jana , McFarland Elizabeth G , Gianfelice David , Lepanto Luigi , Reinhold Caroline
Published: May 2016

This article provides an overview of recently developed,
noninvasive imaging modalities for the evaluation of gastrointestinal
disease processes. The advent of spiral computed
tomography, magnetic resonance cholangiopancreatography and
conventional magnetic resonance imaging has facilitated the
noninvasive assessment of pancreaticobiliary disease. Magnetic
resonance cholangiopancreatography provides projectional images
of the biliary tree and pancreatic duct, similar to those
achieved by direct cholangiography, without the need to administer
contrast medium. Spiral computed tomographic colonography
provides virtual colonoscopic images of the colonic mucosa, allowing
the detection of polyps without the risk associated with
colonoscopy.
Ineffectiveness of hepatitis B vaccination in cirrhotic patients waiting for liver transplantation
Authors: Villeneuve Edith , Vincelette Jean , Villeneuve Jean-Pierre
Published: May 2016

Cirrhotic patients who undergo liver transplantation are at risk of acquiring de novo hepatitis B virus (HBV) infection at the time of transplantation. It is common practice to immunize these patients against HBV, but the efficacy of vaccination is uncertain. The response to vaccination with a recombinant HBV vaccine was examined in 49 patients with cirrhosis before liver transplantation. Patients received three doses (20 µg) of Engerix-B (SmithKline Beecham) at zero, one and two months before transplantation, and their response was measured on the day of liver transplantation (9.3±1.2 months after the initial dose of vaccine). Results were compared with those reported in healthy adults vaccinated according to the same schedule. Fourteen of 49 cirrhotic patients (28%) developed antibodies to hepatitis B surface antigen (anti-HBs) levels of more than 10 U/L after vaccination compared with 97% of healthy controls. Four patients (8%) had anti-HBs levels of more than 100 U/L compared with 83% in healthy individuals. Mean anti-HBs titre in the 14 responders was 62 U/L compared with 348 U/L in controls. No factor was identified that predicted response to vaccination. One of 49 patients acquired de novo HBV infection at the time of liver transplantation. Current HBV vaccination of cirrhotic patients waiting for liver transplantation is ineffective, and new strategies need to be developed to increase the response rate.
Hepatitis C
Authors: Lavanchy Daniel , Gavinio Pilar
Published: May 2016

Hepatitis C has been identified as the most common cause of post-transfusion hepatitis worldwide, accounting for approximately 90% of this disease in Japan, the United States and Western Europe. Hepatitis C is a major global public health problem. New infections continue to occur, and the source of infection includes transfusion of blood or blood products from unscreened donors; transfusion of blood products that have not undergone viral inactivation; parenteral exposure to blood through use of contaminated and inadequately sterilized instruments and needles used in medical, dental and ‘traditional’ medicine; procedures such as hemodialysis; high risk sexual practices; household or sexual contacts of hepatitis C virus (HCV)-infected persons; and infants of HCV-infected mothers. In many countries, the relative contribution of the various sources of infection has not been defined with population-based epidemiological studies. Such studies are necessary to enable countries to prioritize their preventive measures and to make the most appropriate use of available resources. Given the substantial morbidity and mortality attributable to HCV-related chronic liver disease, each country, irrespective of economic status, should develop a plan of HCVrelated public health activities for the prevention of newHCVinfections and the treatment of established chronic infections.
Neonatal Cholestasis: A Red Alert for the Jaundiced Newborn
Authors: Pashankar Dinesh , Schreiber Richard A
Published: May 2016

Neonatal jaundice may indicate cholestasis rather
than a benign, physiological condition. Any four‐week‐old newborn
with persistent jaundice should have a fractionated bilirubin
screen to determine whether the hyperbilirubinemia is unconjugated.
Conjugated hyperbilirubinemia, a hallmark of neonatal
cholestasis, is pathological and requires further investigation.
These infants need prompt diagnosis, early intervention and careful
follow‐up to ensure continued growth and development. Recent
progress in the physiology of bile flow is reviewed, and the
evaluation and management of neonatal cholestasis are summarized.
Further advances in delineating the cellular and molecular
processes that regulate bile acid metabolism in both health and
disease will lead to a greater understanding of the conditions causing
neonatal cholestasis. Unravelling the etiopathogenesis of
these neonatal cholestatic disorders will allow the development of
novel diagnostic and therapeutic interventions that ultimately
will effectuate the prognosis for these young patients.
Clinical Biology and Potential Use of Thrombopoietin
Authors: Basser Russell
Published: May 2016

The discovery
of platelet growth factors raised expectations that an effective
method for abrogating thrombocytopenia would soon be available
in the clinic. The cytokines initially described were pleiotropic in
nature, and stimulation of platelet production was generally modest.
However, one of these agents, interleukin‐11, was successfully
shown to reduce the incidence of severe thrombocytopenia in patients
receiving dose‐intensive chemotherapy, and has now received
approval from the United States Food and Drug Administration
for this purpose. Initial clinical trials of thrombopoietin,
the central regulator of megakaryocytopoiesis and thrombopoiesis,
and its analogues showed these agents to be the most potent
stimulators of thrombopoiesis and to be associated with few adverse
effects. They have also been shown to enhance platelet recovery
after chemotherapy, but early results from trials investigating
their ability to prevent severe thrombocytopenia associated
with the treatment of leukemia and bone marrow transplantation
have been disappointing. In addition, subcutaneous administration
of one of these agents, megakaryocyte growth and development
factor, has been shown to induce the formation of antibodies
that neutralize native thrombopoietin and cause thrombocytopenia.
Platelet growth factors remain promising therapeutic
agents; however, there are a number of obstacles to overcome before
they find general use in the clinic.
Long Term Safety of Infliximab
Authors: Schaible Thomas F
Published: May 2016

Infliximab is a chimeric anti-tumour necrosis factor-alpha monoclonal antibody that has been studied for the treatment of Crohn’s disease and rheumatoid arthritis. In several placebo controlled, randomized clinical trials and open trials, 771 patients have been given infliximab (a further 192 received placebo). Follow-up for safety has included the time of study (12 weeks after the last infusion), plus three additional years. Acute infusion reactions (headache, fever, chills, urticaria, chest pain) were seen in17% of patients receiving infliximab compared with 7% of those receiving placebo. While infections were reported more frequently overall in the patients given infliximab (26% over 27 weeks of follow-up versus 16% of placebo-treated patients over 20 weeks of follow-up), there was no increased risk of serious infections. There was no difference in the overall mortality rate between the groups. While low titres of autoantibodies developed in less than 10% of patients, drug-induced lupus was seen in less than 1%, with these cases resolving upon discontinuation of the drug. Overall, infliximab showed an acceptable safety profile.
Diagnosis and Management of Chronic Hepatitis C
Authors: Pár Alajos
Published: May 2016

This mini-review is devoted to the main questions of diagnosis, treatment and prevention of chronic hepatitis C (CHC). Diagnosis of CHC is based on virological, biochemical and histological findings. The etiology of CHC should be proven by the presence of antibody to hepatitis C virus (anti-HCV) and detection of viral nucleic acid (HCV RNA), using qualitative and quantitative polymerase chain reaction or branched chainDNAtechniques. Serum aminotransferase levels can reflect the biochemical activity of liver disease, while biopsy is very important in the grading and staging of the pathological process. The generally accepted treatment ofCHCis interferon (IFN); however, recently, the combination of IFN with the oral nucleoside analogue ribavirin has become the therapy of choice, not only for relapsers but also for naive patients. Prevention of hepatitis C by vaccination is not yet available. Screening blood donors and members of high risk groups, as well as ensuring good public health measures, are imperative to inhibit the spread of HCV.
The Role of Surgery in the Management of Acute Pancreatitis
Authors: Gloor Beat , Uhl Waldemar , Müller Christophe A , Büchler Markus W
Published: May 2016

The clinical course of an episode
of acute pancreatitis varies from a mild, transitory form to a
severe necrotizing form characterized by multisystem organ failure
and mortality in 20% to 40% of cases. Mild pancreatitis does
not need specialized treatment, and surgery is necessary only to
treat underlying mechanical factors such as gallstones or tumours
at the papilla of Vater. On the other hand, patients with severe
necrotizing pancreatitis need to be identified as early as possible
after the onset of symptoms to start intensive care treatment. In
this subgroup of patients, approximately 15% to 20% of all patients
with acute pancreatitis, stratification according to infection
status is crucial. Patients with infected necrosis must
undergo surgical intervention, which consists of an organpreserving
necrosectomy followed by postoperative lavage
and/or drainage to evacuate necrotic debris, which appears during
the further course of the condition. Primary intensive care
treatment, including antibiotic treatment, delays the need for
surgery in most patients until the third or fourth week after the
onset of symptoms. At that time, necrosectomy is technically
easier to perform and the bleeding risk is reduced, compared with
necrosectomy earlier in the disease course. In patients with sterile
necrosis, the available data strongly support a conservative
approach (ie, intensive care unit treatment). Surgery is rarely
necessary in these patients.
Patients with Chronic Hepatitis C - Who Should Not Be Treated?
Authors: Schüler Andreas , Manns Michael Peter
Published: May 2016

The decision to treat a patient with chronic hepatitis C (CHC) is based on what is known about the risk factors for developing liver cirrhosis or hepatocellular carcinoma, as well as on conditions that contraindicate therapy or impair therapy effectiveness. Several factors, including age, treatment side effects, disease severity, concurrent diseases and life conditions, may render treatment decisions more difficult. This review focuses on identifying CHC patients who should not receive treatment.
Sex‐Related Liver Injury Due to Alcohol Involves Activation of Kupffer Cells by Endotoxin
Authors: Thurman Ronald G
Published: May 2016

Females have a greater susceptibility
to ethanol‐induced liver injury than males. Females who
drink ethanol regularly and have been overweight for 10 years or
more are at greater risk for both hepatitis and cirrhosis than males,
and females develop ethanol‐induced liver injury more rapidly and
with less ethanol than males. Female rats on an enteral ethanol protocol
exhibit injury more quickly than males and have widespread
fatty changes over a larger portion of the liver lobule. Moreover,
levels of plasma endotoxin, intracellular adhesion molecule‐1, free
radical adducts, infiltrating neutrophils and nuclear factor kappa B
are doubled in female rat livers compared with male rat livers after enteral
ethanol treatment. Additionally, estrogen treatment in vivo increases
the sensitivity of hepatic macrophages or Kupffer cells to
endotoxin. Evidence has been presented that Kupffer cells are pivotal
in the development of ethanol‐induced liver injury. Destroying Kupffer
cells with gadolinium chloride or decreasing bacterial endotoxin
by sterilizing the gut with antibiotics inhibits early inflammation due
to ethanol. Similar results have been obtained with anti‐tumour necrosis
factor‐alpha antibody. These data pointed to the hypothesis
that ethanol‐induced liver injury involves elevations in circulating
endotoxin concentrations leading to activation of Kupffer cells,
which causes a hypoxia‐reoxygenation injury. This theory has been
tested using pimonidazole, a 2‐nitroimidazole marker, to quantify hypoxia
in downstream, pericentral regions of the hepatic lobule. After
chronic enteral ethanol treatment, pimonidazole binding doubles.
Enteral ethanol also increases free radicals detected with electron
spin resonance. Radical adducts, with coupling constants such as
alpha‐hydroxyethyl radical, have been shown to arise from ethanol.
Importantly, hypoxia and radical production detected in bile are also
decreased by the destruction of Kupffer cells with gadolinium chloride.
These data support the hypothesis that Kupffer cells contribute
to the vital sex differences in liver injury caused by ethanol.
Hepatocellular Bile Salt Transport: Lessons from Cholestasis
Authors: Trauner Michael , Fickert Peter , Stauber Rudolf E
Published: May 2016

Hepatic uptake and excretion of
bile salts and several nonbile salt organic anions (eg, bilirubin) are
mediated by a distinct set of polarized transport systems at the basolateral
and apical plasma membrane domains of hepatocytes and
bile duct epithelial cells (cholangiocytes). With the increasing
availability of molecular probes for these transporters, evidence
now exists that decreased or even absent expression of hepatobiliary
transport proteins in hepatocytes or cholangiocytes may
explain impaired transport function that results in hyperbilirubinemia
and cholestasis. This review summarizes the molecular defects
in hepatocellular membrane transporters that are associated with
hereditary and acquired forms of cholestatic liver disease.
Medical Management of Chronic Cholestatic Liver Diseases
Authors: Gossard Andrea A , Lindor Keith D
Published: May 2016

The purpose of the present review is to discuss the diagnosis
and management of cholestatic liver diseases. Differential diagnoses
to consider are described, including causes of extrahepatic
biliary obstruction such as gallstones, strictures, extrabiliary malignancies
and pancreatitis. In addition, diseases that cause intrahepatic
cholestasis such as primary biliary cirrhosis, primary
sclerosing cholangitis, hepatocellular diseases and a variety of miscellaneous
causes including drugs that may cause cholestasis are
discussed. Primary biliary cirrhosis and primary sclerosing
cholangitis are reviewed in detail, and management options are
identified. The prognosis of patients with these diseases is discussed,
and the Mayo Mathematical Models in Cholestatic Liver
Disease for both primary biliary cirrhosis and primary sclerosing
cholangitis are provided. Finally, management options for the
complications of cholestasis are provided.
Pregnancy and the Biliary Tract
Authors: Gilat Tuvia , Konikoff Fred
Published: May 2016

Pregnancy induces
many physiological changes, some of which may have pathological
results. In population studies, gallstones were found in
6.5% to 8.4% of nulliparous women, and in 18.4% to 19.3% of
women with two to three or more pregnancies. In women followed
throughout pregnancy, neoformation of gallstones was documented
in 3% to 8.1% depending on the population. Some 20% to 30% of
these gallstones redissolve postpartum. The frequency of biliary colic
during pregnancy is controversial, and the recommended therapeutic
approach during pregnancy is conservative. When essential,
invasive procedures are relatively well tolerated, preferably during
the second trimester. Biliary sludge disappears postpartum in the
great majority. Gallstones and sludge are most likely caused by biliary
stasis, prolonged intestinal transit and increased cholesterol
saturation of bile, which were all demonstrated to occur during
pregnancy.
Iron and Liver Diseases
Authors: Fargion Silvia , Mattioli Michela , Fracanzani Anna Ludovica , Fiorelli Gemino
Published: May 2016

A
mild to moderate iron excess is found in patients with liver diseases
apparently unrelated to genetic hemochromatosis. Iron appears to
affect the natural history of hepatitis C virus‐related chronic liver
diseases, alcoholic liver disease and nonalcoholic steatohepatitis
by leading to a more severe fibrosis and thus aiding the evolution
to cirrhosis.Ahigher frequency of mutations of the HFE gene, the
gene responsible for hereditary hemochromatosis, is found in patients
with liver diseases and increased liver iron than in normal
patients. Patients with excess iron are potentially at a higher risk
of developing hepatocellular carcinoma. Iron depletion therapy
could interfere with fibrosis development and possibly reduce the
risk of liver cancer occurrence.
Management of Perianal Crohn's Disease
Authors: Rutgeerts Paul
Published: May 2016

Perianal inflammation is a disabling manifestation of Crohn’s disease. The primary lesions found in perianal Crohn’s disease evolve in parallel with the disease elsewhere in the bowel. Although the spontaneous resolution of anal lesions is observed in up to half of patients, the penetrating nature of the disease may lead to secondary lesions including complex fistulae. In some patients, this, in turn, results in the gradual destruction of the sphincter apparatus and anal incontinence. These patients, after years of suffering, often require proctectomy. Control of activity, overall, is the first step in the management of perianal Crohn’s disease. Sepsis should be controlled by the drainage of abscesses and by long term use of setons. Although antibiotics and standard immunosuppression often improve perianal fistulae, their action is usually slow and incomplete. Management of perianal Crohn’s disease has changed thoroughly in the past two years since the introduction of monoclonal antibodies to tumour necrosis factor (infliximab). Complete arrest of the drainage of fistulae was obtained in 46% of patients after the administration of 5 to 10 mg/kg of infliximab at weeks 0, 2 and 6, with a median duration of effect of 12 weeks. In these patients, long term management of their bowel disease will likely require the repeated use of infliximab. Studies to evaluate this are underway.
Who Gets Irritable Bowel Syndrome and Does Seeing a Gastroenterologist Affect Its Course?
Authors: Bernstein Charles N
Published: May 2016

A review of studies
involving patients with irritable bowel syndrome is presented.
This review looks at the impact of gastroenterology consultation
on health care utilization patterns and the well‐being of the
patient when followed up over a two‐year period. A structured
gastroenterological consultation between the physician and
patient may decrease the number of office visits for gastrointestinal‐
related problems.
Socioeconomic Impact of Irritable Bowel Syndrome in Canada
Authors: Boivin Michel
Published: May 2016

Irritable bowel syndrome (IBS) is the most common functional
gastroenterological disorder reported to physicians. In Canada,
its prevalence is about 6%. In the United States and the United
Kingdom, the prevalence is estimated to be closer to 15%.
Patients with IBS tend to make extensive use of health care services,
even though a high percentage of them do not seek medical
advice. The costs of IBS are a large expenditure of scarce
resources. These costs can be divided into several categories:
direct, indirect and intangible costs. The direct costs, associated
with the diagnosis and treatment, are largely sustained by the
health care system. The indirect costs are related to the production
losses due to morbidity, and intangible costs are associated
with the pain, suffering and alteration in the patient’s quality of
life. The condition is a diagnosis of exclusion, and treatment,
although beneficial, is rarely curative. The general treatment
approach stresses the importance of a good physician‐patient
relationship. Exploring the nature of the expenses associated
with IBS and understanding how treatment options may affect
these costs are essential to reducing its financial burden.
Irritable Bowel Syndrome: New Approaches to Its Pharmacological Management
Authors: Tougas Gervais
Published: May 2016

The present paper examines
approaches to drug therapy for irritable bowel syndrome (IBS).
Because IBS is associated with multiple symptoms, no single
therapy is effective in all patients. However, issues such as affective
and emotional factors also need to be addressed when treating
patients with IBS. This paper emphasizes the importance of
identifying new pharmaceutical approaches to treat a multitude
of symptoms and obtaining a better understanding of the underlying
mechanisms of IBS.
Community‐Acquired Pneumonia in Children: A Multidisciplinary Consensus Review
Authors: Low Donald E , Kellner James D , Allen Upton , Boucher Francois D , Kovesi Thomas , Riesman John , Davidson Ross , Langley Joanne M
Published: May 2016

Community‐acquired pneumonia (CAP) is common among children and may have viral, bacterial or, occasionally, other causes. The etiology is complex, with age‐related trends, and differs from that in adult CAP, necessitating different management guidelines. There is an absence of current guidelines for the management of pediatric CAP (PCAP) that take into account changing etiologies, antimicrobial‐resistance issues and the use of newly licensed antimicrobials. The present review does not provide specific guidelines, but it reviews the literature and presents currrent approaches to the treatment of PCAP. To compile the review, an expert panel was convened to provide a consensus. The review discusses the etiology, diagnosis and antimicrobial treatment of PCAP as well as indications for referral to a hospital emergency department. The goal of the review is to provide those involved with treatment of PCAP in the community setting with information that can be used to make effective treatment choices.
Clostridium difficile in Clinical Practice: Increasing Rates, More Virulent Organisms and New Therapies on the Horizon
Authors: Louie Thomas J
Published: May 2016

Clostridium difficile‐associated diarrhea has recently come under
increasing scrutiny because of outbreaks of disease in eastern Canada
in association with a hypervirulent ribotype 027 (NAP1) strain.
Hospitals in the United States, the United Kingdom and Europe have
been affected as well. Epidemiological studies are underway to determine
the presence of the more virulent strain of C difficile in hospitals
across Canada. Because this strain is highly quinolone resistant, it is
suspected that overuse of that class of antimicrobial agent may be a
selection factor for this strain. Although C difficile‐associated diarrhea
is usually considered a nosocomial infection, approximately one‐quarter
of cases occur in the community. Recurrence following successful resolution
of diarrhea occurs in one in five patients treated with metronidazole
or vancomycin; relapse is more common in patients needing
retreatment. New therapies that may have equivalent or higher
response rates and lower recurrence rates are being investigated. It is
hoped that these new treatments will be a substantial improvement
over current therapies. In the interim, prudent antimicrobial use and
attention to infection control practices are the main preventive
strategies. Prompt testing for C difficile toxin in patients with diarrhea
after antibiotic exposure, discontinuation of unnecessary antibiotic
therapy and rapid initiation of treatment should minimize complications.
With the appearance of more toxigenic strains of C difficile,
careful monitoring of patients to detect suboptimal clinical response is
necessary.
Canadian Patterns of Antimicrobial Resistance: Overview of Current Trends Related to Hospital Pathogens
Authors: Mazzulli Tony
Published: May 2016

Selection of appropriate empirical antibiotic therapy is dependent on
many factors, not the least of which is an understanding of antimicrobial
resistance rates in the patient population that is undergoing treatment.
Resistance rates may vary by geographical location, institution,
hospital ward or unit, and even body site of infection. The present
paper reviews the currently available Canadian data regarding resistance
rates for some of the most common hospital‐acquired pathogens,
including Escherichia coli, Klebsiella species, Pseudomonas aeruginosa,
Enterobacter species, Staphylococcus aureus and Enterococcus species.
Current data suggest that the rates of extended‐spectrum beta‐lactamases
among E coli and Klebsiella species remain relatively low across
Canada. There are very little data on the epidemiology of ampC
cephalosporinases among Gram‐negative organisms, although combined
American and Canadian data suggest that ceftazidime resistance
rates for Enterobacter species range from 17.1% to 24.8%. The
increased use of fluoroquinolones has led to an increase in resistance
rates among most Gram‐negative organisms. In the late 1990s,
ciprofloxacin resistance rates for P aeruginosa were reported to be
approximately 20%. For the Gram‐positive organisms, methicillin
resistance rates for S aureus have been reported to be as high as 10%
and vancomycin resistance rates for Enterococcus species have been
reported to be less than 1%. Additional data that are representative of
all regions of Canada are needed. Continued surveillance, antibiotic
stewardship, and adherence to good infection prevention and control
measures will lead to a better understanding of the epidemiology of
antimicrobial resistance in Canadian hospitals, as well as help to control
its spread.
General Management Strategies for Efavirenz Therapy and Associated Adverse Events
Authors: Baril Jean-Guy , Rachlis Anita
Published: May 2016

Efavirenz therapy‐related central nervous system symptoms often
occur shortly after initiation of treatment; therefore, the timing of
therapy initiation must be carefully considered so that if side effects do
occur, it is at a time when the patient is not mentally overburdened
and when support is readily available. Current literature contains contradictory
data on the relationship between plasma levels of efavirenz
and the occurrence of neuropsychiatric adverse events; therefore, routine
measurement of plasma concentrations is not recommended
except under certain circumstances. Clinician management of general
neuropsychiatric symptoms comprises four steps: preparation, education,
reassurance and treatment. Among the specific central nervous
system symptoms that are known to occur with efavirenz therapy are
agitation, sleep disturbances, dreams, dizziness, impaired concentration
and depression. There are recommended pharmacological and
nonpharmacological protocols for managing these symptoms. Prompt,
successful management of treatment‐emergent neuropsychiatric symptoms
is important so that the patient may receive the optimal longterm
viral suppression that is possible with efavirenz therapy.
Extended‐Spectrum Beta‐Lactamases
Authors: Forward Kevin R
Published: May 2016

The definition of extended‐spectrum beta‐lactamases (ESBLs) has
expanded rapidly, in terms of both the number and the variety of
enzymes. Bacteria bearing plasmidic ESBLs are spreading widely
throughout the world. In Canada, the problem has grown less rapidly
than in other parts of the world; however, ESBLs still present a significant
impediment to the treatment of serious infections with extendedspectrum
cephalosporins and penicillins. Although SHV‐derived
enzymes were the primary concern in the late 1980s and early 1990s,
these enzymes have been rapidly overtaken by the CTX‐M family of
ESBLs. There is no reason to believe that the problem of ESBLs will
not expand rapidly in the face of intense antimicrobial pressure and
lapses in infection control practices. Control should focus on early
detection, accurate characterization, effective treatment and measures
to prevent further spread.
Managing Psychotropic Drugs with Efavirenz
Authors: Therrien Rachel
Published: May 2016

Efavirenz is in the non‐nucleoside reverse transcriptase inhibitor category
of HIV antiretroviral medicines. It is an in vivo inducer of the
CYP3A4 isoenzyme within the cytochrome P450 (CYP450) system,
and an in vitro inhibitor of the system’s CYP2C9/2C19, 3A4 and 2B6
isoenzymes; as a result, concentrations of psychotropic drugs can be
increased or decreased depending on the specific enzyme pathway
involved in their metabolism. CYP3A4 is responsible for metabolizing
many benzodiazepines and other psychotropics, as well as selective
serotonin reuptake inhibitors and tricyclic antidepressants. As an
inducer of CYP3A4, efavirenz can increase the rate at which these
agents are metabolized, resulting in administered psychotropic drug
levels that are below their therapeutic thresholds. Conversely,
efavirenz is an inhibitor of CYP2B6, which metabolizes agents such as
bupropion; consequently, bupropion levels in the blood can increase.
Given the existing conflicting data, the clinician may find it impractical
to use an evidence‐based approach when concomitantly prescribing
efavirenz and psychotropic drugs to their HIV patients. Instead, it
may be preferable to use a more pragmatic approach that applies knowledge
of the most current pharmacological and pharmacokinetic data for
psychotropics and non‐nucleoside reverse transcriptase inhibitors,
which may help better predict their potential interactions.
Vancomycin‐Resistant Enterococci: The Value of Infection Control and Antibiotic Control Policy
Authors: Weiss Karl
Published: May 2016

Vancomycin‐resistant enterococci (VRE) represent a major challenge
for the Canadian health care system. The clinical significance of VRE
in the Canadian health care system has increased over the past two
decades, with outbreaks reported in Ontario and Quebec, although
most provinces have been affected. This organism has been a substantial
human and financial burden for Canadian institutions. VRE have
been shown to be associated with an increased mortality, a longer hospital
stay and a much higher overall cost compared with vancomycinsusceptible
strains.
Enterococci are now the third most important nosocomial pathogen
in American intensive care units. The two most common species,
Enterococcus faecalis and Enterococcus faecium, have shown remarkable
adaptability in responding to antibiotics. The arrival of VRE in
Canada has forced hospitals to implement stringent and costly infection
control measures. A multifaceted approach, including antibiotic
restriction and stringent infection control measures, is important in
managing VRE prevalence in Canadian institutions.
Triple Active Antiretroviral Regimen Including Enfuvirtide via the Biojector is Effective and Safe
Authors: Loutfy Mona , Kovacs Colin
Published: May 2016

For full HIV virological suppression, three fully active antiretroviral agents are required. New drug classes should be included to ensure that agents are fully active. The addition of enfuvirtide and efavirenz to the present patient’s new antiretroviral regimen ensured that two fully active agents were in use in the setting of a moderate degree of nucleoside resistance and a high level of protease resistance, and where non-nucleoside reverse transcriptase inhibitors were still fully active. Both viral load and CD4 count responded favourably to this regimen. The patient received support from physicians and clinic staff in the introduction and use of enfuvirtide. To reduce injection site reactions, a needle-free injection system (Biojector) proved effective.
Diffuse Large B Cell Lymphoma Mimicking Granulomatosis with Polyangiitis
Authors: Naffaa Mohammad E. , Rozin Alexander P. , Horowitz Netanel , Ben-Itzhak Ofer , Braun-Moscovici Yolanda , Balbir-Gurman Alexandra
Published: May 2016

In a patient with systemic multiorgan disease with overlapping features, the differential diagnosis included infectious diseases, malignancies, and systemic autoimmune or inflammatory diseases. We present an unusual case of a young male with B cell lymphoma who presented with symptoms mimicking systemic vasculitis and review the existing literature.
Strengthening Mechanisms of Magnesium-Lithium Based Alloys and Composites
Authors: Muga C. O. , Zhang Z. W.
Published: May 2016

Mg-Li based alloys are widely applied in various engineering applications. The strength of these alloys is modified and enhanced by different strengthening mechanisms. The strengthening mechanisms of these alloys and their composites have been extensively studied during the past decades. Important mechanisms applied to strengthening the alloys include precipitation strengthening, solution strengthening, grain and subgrain strengthening, and dislocation density strengthening. Precipitation and solution strengthening mechanisms are strongly dependent on composition of the alloys and thermal treatment processes, whereas grain and subgrain and dislocation density strengthening mechanisms majorly depend on thermomechanical processing. In this paper, recent studies on conventional processes for the strengthening of Mg-Li based alloys are summarized as they are critical during the alloys design and processing. Main strengthening mechanisms are objectively reviewed, focusing on their advantages and drawbacks. These can contribute to enhancing, initiating, and improving future researches for alloys design and suitable processing selection.