Routine ultrasound-guided liver biopsy: a time whose idea has come?

Percutaneous liver biopsy is a commonly performed procedure in modern hepatology. Although it is a safe procedure and performed in most cases on an outpatient basis, complications including mortality have been reported. It is widely perceived that the use of ultrasound guiding for the biopsy produces a decrease in complications and is safer. There is now a trend for more centers to adopt a policy of ultrasound-guided biopsies only. There are, however, no official guidelines that recommend such a policy. This trend for ultrasound guidance of invasive procedures is also becoming apparent in other areas such as the insertion of a central venous line in children. The literature in support of such a position is far from conclusive. Because there are medicolegal and economic implications for the policy of routine ultrasound guiding of biopsies, we suggest that there is a need for the major professional organizations to make a clear declaration on this issue.     

Tissue-specific hemostasis in mice

Blood coagulation is essential to maintain hemostasis in organisms with a vascular network. Formation of a fibrin-rich clot at a site of vessel injury is a highly complex process that is orchestrated by the coagulation protease cascade. This cascade is regulated by 3 major anticoagulant pathways. Removal of a clot is mediated by the fibrinolytic system. Defects in the regulation of clot formation lead to either hemorrhage or thrombosis. Tissue factor, the primary cellular initiator of blood coagulation, is a transmembrane receptor that is expressed in a tissue-specific manner. The 3 major anticoagulants are tissue factor pathway inhibitor, antithrombin, and protein C, the latter requiring a transmembrane receptor called thrombomodulin for its activation. Tissue factor pathway inhibitor and thrombomodulin are expressed by endothelial cells in a tissue-specific manner, whereas antithrombin and protein C circulate in the plasma. Fibrinolysis requires the activation of plasminogen to plasmin, which is mediated by tissue-type plasminogen activator and urokinase-type plasminogen activator. Interestingly, tissue-type plasminogen activator is expressed by a subset of endothelial cells of discrete size and location. These observations, together with the phenotypes of mice that have defects in the procoagulant, anticoagulant, and fibrinolytic pathways, indicate that hemostasis is regulated in a tissue-specific manner.     

A family of tissue-specific resistin-like molecules

We have identified a family of resistin-like molecules (RELMs) in rodents and humans. Resistin is a hormone produced by fat cells. RELMalpha is a secreted protein that has a restricted tissue distribution with highest levels in adipose tissue. Another family member, RELMbeta, is a secreted protein expressed only in the gastrointestinal tract, particularly the colon, in both mouse and human. RELMbeta gene expression is highest in proliferative epithelial cells and is markedly increased in tumors, suggesting a role in intestinal proliferation. Resistin and the RELMs share a cysteine composition and other signature features. Thus, the RELMs together with resistin comprise a class of tissue-specific signaling molecules.     

Importance of Internal Variability in Clinical Trials of Cardiovascular Disease

A well conducted randomised controlled trial (RCT) is extremely important in the field of cardiovascular medicine. At the same time, it is equally important to understand the strengths and limitations of any RCT, and internal variability is a concept in clinical trials that is poorly understood. Variability in a clinical trial may be introduced at an individual level or during measurement, sampling, or conduct of the trial. It is not the same as internal validity, which is a broader concept of accuracy; to be valid, a study should minimise variability and have sound methodology. There are various steps that may be followed to minimise the internal variability in a clinical trial. One aspect of great importance is the adjudication process, which should be done meticulously and is often a step that is overlooked. It is important to standardise each step as much as possible, to ensure consistency and reduce noise at all levels. The concepts discussed in this review may serve as a roadmap to limit the influence of internal variability and maximise internal validity of RCT results.     

Experimental Study on Carbonation of Cement-Based Materials in Underground Engineering

The corrosive water environment has a decisive influence on the durability of a diversion tunnel lining. In this paper, the effects of carbonation on cement-based materials in water-immersion and saturated-humidity environments were studied by increasing the CO₂ concentration. The results show that under conditions of water-immersion and saturated humidity, the color of the non-carbonation region is dark, while the carbonation region is gray, and the color boundary is obvious. However, in an atmospheric environment, there is no zone with a dark color and the color boundary is not obvious. In a saturated-humidity environment, the carbonation depth increases over time and changes greatly, and its value is about 16.71 mm at 200 days. While in a water-immersion environment, the carbonation depth varies little with time and the value is only 2.31 mm. The carbonation depths of cement mortar samples in different environments generally follow a linear relationship with the square root of time. The carbonation coefficient in a saturated-humidity environment is more than nine times that in the water-immersion environment. In a water-immersion environment, the carbonation causes a large loss of calcium in cement-based materials, and their Ca/Si ratio obviously decreases. The calcium silicon ratio (Ca/Si) of cement-based materials in a water-immersion environment is 0.11, which is much less than 1.51 in a water-saturated environment and 1.49 in an atmospheric environment. In a saturated-humidity environment, the carbonation only reduces the pH of the pore solution in the carbonation region, and the structural stability of cement-based materials is not degraded. The number of pores of all radii after carbonation in a water-immersion environment exceeds that in a saturated-humidity environment, and the total pore volume and average pore radius in a water-immersion environment are also larger than in a saturated-humidity environment, so the water-immersion environment accelerates the development and expansion of pores. The research results can provide some theoretical and technical support for the design, construction, and safe operation of diversion tunnel linings.     

Vascular calcification: expression patterns of the osteoblast-specific gene core binding factor alpha-1 and the protective factor matrix gla protein in human atherogenesis.

OBJECTIVE: Increasing evidence suggests that vascular calcification is a regulated process. We studied the vascular expression pattern of a key factor in mineralization and a counteracting, protective factor. Based on the phenotype of null mice, Core binding factor alpha-1 (Cbfa-1) plays a pivotal role in bone formation, whereas Matrix Gla Protein (MGP) is a potent inhibitor of vascular calcification. METHODS: We investigated the expression of MGP and Cbfa-1 in cultured, human monocytic cells, endothelial cells and smooth muscle cells (SMC), as well as in normal and atherosclerotic vessel specimens. RESULTS: In cultured cells MGP is expressed in endothelial cells and SMC, whereas Cbfa-1 mRNA is predominantly present in macrophages and to a lesser extent in SMC. In the normal vessel wall MGP expression is high at the luminal side and declines toward the center of the media, whereas Cbfa-1 is absent. Moderate, diffuse calcification of the aorta media was observed only in those regions where MGP is low or absent. In atherosclerotic lesions MGP is expressed in endothelial cells and SMC that form fibrous caps, but is never present in macrophages. Cbfa-1 is synthesized in regions without MGP, it is associated with calcified areas and Cbfa-1 may be considered a marker for osteoprogenitor-like cells in the vessel wall. CONCLUSIONS: Our observations on MGP expression confirm and extend published data and are consistent with a protective function of MGP. Cbfa-1 expression is absent in normal medial SMC and co-localizes with neointimal macrophages and focal calcifications.     

Anger in palliative care: a clinical approach

Anger in patients and families is a common problem in the care of persons with advanced disease. Whereas it is widely accepted that anger may be a justifiable reaction to significant illness and loss, it frequently creates difficulties for the doctors involved in care. In particular, there is often a personal impact on the doctor at whom anger is directed. This paper examines results of qualitative research with palliative care workers in the context of the broader published literature and the authors' clinical experiences. The ability to interact effectively with angry patients is a skill that is often learned with experience and is extremely useful in both transforming the patients' reaction into a more creative emotion and in developing a therapeutic relationship. Despite conscientious efforts, however, a few patients continue to be angry. A practical approach to anger, useful for the clinician directly involved in care, is outlined along with some strategies to adopt in the face of persistent anger.     

Iron deficiency anemia in older adults: A review

Anemia in older adults is a risk factor for numerous negative outcomes. There is no standard definition, but in most studies, anemia is defined as a hemoglobin value <12 g/dL for women and <13 g/dL for men. Absolute iron deficiency anemia is defined as the combination of anemia and the absence of total body iron. Serum ferritin is the most frequently used diagnostic parameter, but its concentration increases with age and in the presence of inflammatory diseases. Other laboratory tests, such as transferrin saturation, soluble transferrin receptor and the soluble transferrin receptor/ferritin index might provide useful information, but there is a wide variety in the cut‐off values and interpretation of the results. Recent research regarding hepcidin as a central regulator of iron homeostasis is promising, but it has not been used yet for the routine diagnosis of iron deficiency anemia. In older iron deficiency anemia patients, an esophagogastroduodenoscopy and colonoscopy should be initiated in order to identify the underlying bleeding cause. CT colonography can replace a colonoscopy, and in specific cases, a video capsule is recommended. It remains crucial to keep in mind which potential benefits might be expected from these investigations in this vulnerable population, taking into account the comorbidity and life expectancy, and one should discuss in advance the possible therapeutic options and complications with the patient, a family member or a proxy. Oral iron administration is the standard treatment, but parenteral iron is a convenient and safe way to provide the total iron dose in one or a few sessions. Geriatr Gerontol Int 2018; 18: 373–379 .     

Microbiota and enteral nutrition

Enteral nutrition is a nutritional therapy that is used in up to 10% of hospitalized patients. It involves a dramatic change in the provision of nutrients to the intestine and this, along with metabolic stress and drugs used, is responsible for a marked dysbiosis. Even though there is a huge level of between-subject variability, this dysbiosis is characterized by a decrease in the dominant flora, an increase in potentially pathogenic microorganisms and a reduction in the number of individual strains. The main characteristic of these changes in the microbiota is diarrhea, which has many consequences in these patients. Saccharomyces boulardii is able to prevent enteral nutrition-associated diarrhea, probably through an increase in short-chain fatty acid production. Alongside its role in the onset and prevention of diarrhea, the microbiota may be involved in energy harvesting and changes in the nutritional status. Manipulations of the microbiota may therefore be a novel way to increase feeding efficiency in tube-fed patients.     

Tissue-type plasminogen activator and neuroserpin: a well-balanced act in the nervous system?

Tissue-type plasmingen activator (tPA) is a highly specific serine proteinase that activates the zymogen plasminogen to the broad-specificity proteinase plasmin. tPA is found in the blood, where its primary function is as a thrombolytic enzyme, as well as in the central nervous system (CNS), where it promotes events associated with synaptic plasticity and cell death in a number of settings, such as cerebral ischemia and seizures. Neuroserpin is a fully inhibitory serine proteinase inhibitor (serpin) that reacts preferentially with tPA, and is located in regions of the brain where either tPA message or tPA protein are also found, suggesting that neuroserpin is the selective inhibitor of tPA in the CNS. There is a growing body of evidence demonstrating the participation of tPA in a number of physiologic and pathologic events in the CNS, and the role of neuroserpin as the natural regulator of tPA's activity in these processes.     

Viable Myocardium: How Much Is Enough?

Left ventricular systolic dysfunction is mainly a result of coronary artery disease (CAD). Decrease in myocardial contractility results as a response to a chronic hypoperfusion state that produces a change in cardiac myocyte metabolism, resulting in a perfusion-contraction mismatch in which function is sacrificed for survival. If revascularization is performed in a timely fashion, metabolism can be restored leading to recovery of function. Through the use of noninvasive imaging modalities, assessing myocardial viability can be easily performed and will aid in selecting those patients who will benefit from revascularization. Viable myocardium can be identified by nuclear modalities that have a high sensitivity but a lower specificity, such as thallium-201 single photon emission computed tomography and positron emission tomography (PET); or by the use of dobutamine stress echocardiogram (DSE), which has a decreased sensitivity but a better specificity. A modality that is increasingly being used with an overall good sensitivity and specificity is contrast-enhanced magnetic resonance imaging. The purpose of this review is to explore the amount of myocardial viability that is relevant to pursue revascularization, since as myocardial function improves there is a decrease in morbidity and mortality from heart failure and arrhythmias.     

Hepcidin and cytokines in anaemia

Hepcidin is a cytokine-induced antibacterial protein which is produced in the liver, circulates in the blood, and is excreted in the urine. It is a major regulator of iron balance in the intestinal mucosa, and appears to have a significant role in the pathogenesis of haemochromatosis and related disorders. Hepcidin appears to be a major contributor to the hypoferraemia associated with inflammation. Serum ferritin concentration is strongly correlated with hepcidin protein levels in either urine or serum, and certain patients with hepatic adenomas exhibit a microcytic, hypoferraemic hepcidin-dependent anaemia. For these reasons, it has been proposed that hepcidin is a primary factor in the pathogenesis of the anaemia of chronic disease (ACD), a cytokine-mediated anaemia commonly encountered in clinical practice and characterized by hypoferraemia with adequate reticuloendothelial iron stores. However, the pathogenetic basis of ACD is not entirely due to changes in iron metabolism, but also involves abnormalities in red cell survival and the erythropoietic response to anaemia. In this review, the evidence for involvement of hepcidin as a major mediator of ACD is evaluated. Hepcidin appears to be a major factor in the systemic iron abnormalities seen in ACD; whether it contributes to the other aspects of the pathogenesis of the syndrome requires further investigation.     

Hepcidin and Cytokines in Anaemia

Hepcidin is a cytokine-induced antibacterial protein which is produced in the liver, circulates in the blood, and is excreted in the urine. It is a major regulator of iron balance in the intestinal mucosa, and appears to have a significant role in the pathogenesis of haemochromatosis and related disorders. Hepcidin appears to be a major contributor to the hypoferraemia associated with inflammation. Serum ferritin concentration is strongly correlated with hepcidin protein levels in either urine or serum, and certain patients with hepatic adenomas exhibit a microcytic, hypoferraemic hepcidin-dependent anaemia. For these reasons, it has been proposed that hepcidin is a primary factor in the pathogenesis of the anaemia of chronic disease (ACD), a cytokine-mediated anaemia commonly encountered in clinical practice and characterized by hypoferraemia with adequate reticuloendothelial iron stores. However, the pathogenetic basis of ACD is not entirely due to changes in iron metabolism, but also involves abnormalities in red cell survival and the erythropoietic response to anaemia. In this review, the evidence for involvement of hepcidin as a major mediator of ACD is evaluated. Hepcidin appears to be a major factor in the systemic iron abnormalities seen in ACD; whether it contributes to the other aspects of the pathogenesis of the syndrome requires further investigation.     

Survivin： Potential role in diagnosis, prognosis and targeted therapy of gastric cancer

Survivin is a protein that is highly expressed in a vast number of malignancies,but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells,thus facilitating the growth of these cells. In the case of gastric cancer,survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells,it has been described as an "ideal target" for cancer therapy. Currently,several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis,prognosis and treatment of gastric tumors.     

Local treatment of carcinoma of the rectum

Conclusions Local treatment of carcinomain situ of the rectum is the procedure of choice. It is also preferable when there is a focal malignant change in a polyp with a pedicle that is not invaded by the cancer, and when a sessile carcinoma of low grade is less than 2 cm. in diameter. These indications may be extended in some cases when the general condition of the patient precludes a radical surgical procedure, when the patient, because of a poor mental condition, would not be able to manage the colostomy himself, and when a colostomy is refused. When a carcinoma of the rectum is inoperable, or when there is distant metastasis, local treatment may provide gratifying palliation. Read at the Canberra meeting of the Royal Australasian College of Surgeons. Canberra, Australia, November 28, 1964.     

Central sleep apnea.

The critical issue in considering the diagnosis and management of CSA is to determine the physiologic process underlying the disorder. CSA includes a pathophysiologically and clinically heterogeneous group of disorders that can be divided into two main groups on the basis of the awake PaCO2: a hypercapnic group, in whom the disorder is related to central alveolar hypoventilation or neuromuscular disease, and a nonhypercapnic group, in whom there is no identifiable underlying disorder. The common feature of these two groups is recurrent episodes of central apnea during sleep related to withdrawal of the wakefulness drive to breathing. In the hypercapnic group the clinical history is dominated by recurrent episodes of respiratory failure and its complications, with the sleep disturbance being a secondary feature. CSA in these patients is simply an exaggeration, by sleep, of their hypoventilation disorder. Treatment in most cases involves mechanical assisted ventilation during sleep, which can be very effective in reversing CSA and respiratory failure. In contrast, idiopathic CSA is characterized by a tendency to hyperventilation. This tendency is reinforced during sleep by recurrent arousals, which tend to propagate the CSA. Unlike hypercapnic CSA, idiopathic CSA is a relatively benign condition in which cardiorespiratory failure is not a feature. Treatment of this disorder is problematic, but the use of nocturnal nasal CPAP appears to be quite effective.     

Paragonimiasis: a view from Columbia

Paragonimiasis is a zoonosis caused by adult trematodes of the Paragonimus genus. The infection in humans is a result of a complex transmission cycle that includes two obligate intermediate hosts, a snail and a crustacean or a crayfish, and a definitive mammalian host. It has been shown that 9 of the more than 40 species of Paragonimus described affect humans in over 39 countries in Asia, Africa and America. It is estimated that 20.7 million people have paragonimiasis and it is calculated that 195 million people are at risk of being infected. The illness usually is caused once the parasite has settled in the lung at the site of the main clinical symptoms: cough, thoracic pain and hemoptysis. The diagnosis of paragonimiasis is based on the patient's history, the parasitological findings (ova in sputum and in feces), and the result of radiological and immunological tests. In severe cases, the patient may suffer from life-threatening hemoptysis or pneumothorax. Currently, praziquantel is the drug of choice.     

Glucose regulation and oxidative stress in healthy centenarians

Aging, oxidative stress and insulin resistance are strongly correlated. There is a growing body of evidence showing that aging is associated with a significant rise in oxidative stress mainly due to a decline in anti-oxidant activity and a rise in pro-oxidant factors such as glucose and insulin concentrations. Furthermore, aging is also associated with a progressive rise in insulin resistance which is due to a complex network of environmental, anthropometric and neuro-hormonal factors. It is noteworthy that extreme longevity, e.g. centenarians, is associated with a low degree of oxidative stress and insulin resistance. The causes for such differences between aged subjects and centenarians is not fully understood. It is likely that a specific genetic background might play a role. However, the insulin gene does not seem to be involved for explaining such age-related differences.     

Deletion of a gene encoding an amino acid transporter in the midgut membrane causes resistance to a Bombyx parvo-like virus

Bombyx mori densovirus type 2 (BmDNV-2), a parvo-like virus, replicates only in midgut columnar cells and causes fatal disease. The resistance expressed in some silkworm strains against the virus is determined by a single gene, nsd-2, which is characterized as nonsusceptibility irrespective of the viral dose. However, the responsible gene has been unknown. We isolated the nsd-2 gene by positional cloning. The virus resistance is caused by a 6-kb deletion in the ORF of a gene encoding a 12-pass transmembrane protein, a member of an amino acid transporter family, and expressed only in midgut. Germ-line transformation with a wild-type transgene expressed in the midgut restores susceptibility, showing that the defective membrane protein is responsible for resistance. Cumulatively, our data show that the membrane protein is a functional receptor for BmDNV-2. This is a previously undescribed report of positional cloning of a mutant gene in Bombyx and isolation of an absolute virus resistance gene in insects.     

The delta (delta) gap: an approach to mixed acid-base disorders

The anion gap (AG) is a helpful, yet underused, clinical tool. Not only does the presence of a high AG suggest a certain differential, but knowledge of the relationship between the rise in AG (delta AG) and the fall in bicarbonate (delta HCO3) is important in understanding mixed acid-based disorders. Simple arithmetic converts this relationship into a numerical value, the delta gap (delta gap). The delta gap = delta AG - delta HCO3. If the delta gap is significantly positive (greater than +6), a metabolic alkalosis is usually present because the rise in AG is more than the fall in HCO3. Conversely, if the delta gap is significantly negative (less than -6), then a hyperchloremic acidosis is usually present because the rise in AG is less than the fall in HCO3. Familarity with the relationship between the changes in AG and HCO3 can be useful in unmasking occult metabolic disorders.