The relationship and epidemiology of acute terminal ileitis and Crohn's disease

The frequency of admission for acute terminal ileitis, Crohn's disease, and acute mesenteric lymphadenitis has been compared from the years 1951 to 1970, and the long-term results of operation for acute terminal ileitis in 1951-1965 have been examined.Whereas the admission rates for both acute terminal ileitis and Crohn's disease rose during the review period, that for acute lymphadenitis tended to fall slightly. Sixty-eight of 72 patients operated upon by appendicectomy who had acute terminal ileitis were followed up. One of these, with small intestinal stenosis at the initial operation, proved to have histological evidence of Crohn's disease, and a further nine have since developed unequivocal evidence of the disease. A cutaneous fistula developed in only one patient after appendicectomy. It is concluded that appendicectomy can safely be performed in acute terminal ileitis provided that the caecum is not inflamed and that Crohn's disease seldom develops as a sequel.     

Chronic pharmacological preconditioning against ischemia

Despite decades of research and thousands of experimental publications, acute preconditioning strategies have yet to be implemented in clinical practice. While some have attributed this to a failure of the experimental studies to mimic the clinical environment, others have suggested that acute preconditioning strategies themselves may possess physiological limitations. In particular, there is evidence to suggest a reduced efficacy of acute preconditioning in the aged heart and in disease states, such as diabetes, hypertension, hyperlipidemia, and atherosclerosis. In addition, pharmacologic agent commonly used in clinical practice, such as sulfonylureas and non-steroidal anti-inflammatory agents may interfere with acute preconditioning signaling pathways. Such considerations may preclude the translation of acute preconditioning strategies to the clinical setting. This has led some to shift attention to alternate strategies of cardioprotection, one such strategy being the possibility of generating a prolonged state of cardioprotection. Although preliminary, studies to date have suggested that sustained preconditioning strategies may not be associated with the same drawbacks as acute preconditioning. Further, cardioprotective signaling pathways that elicit the sustained preconditioning response may be distinct from acute signaling pathways, which permit pharmacologic targeting of these pathways in the future. Additionally, sustained preconditioning strategies may be clinically applicable in the setting of acute myocardial infarction, a setting where acute preconditioning strategies are inherently limited. This review will briefly discuss the current data regarding sustained preconditioning strategies, including those in humans, and discuss the goal of future studies in this setting.     

Severe acute respiratory syndrome: an update

PURPOSE OF REVIEW: An international outbreak of severe acute respiratory syndrome, a recently recognized syndrome caused by the newly identified severe acute respiratory syndrome-associated coronavirus, began in November 2002 and ended in July 2003. Since then, a large body of research on the syndrome has been published; the most updated developments are summarized here. RECENT FINDINGS: Recent findings suggest that animal severe acute respiratory syndrome-like coronaviruses may have been transmitted to humans without detection for years before the recent outbreak, and that such transmission may be continuing today. The 2002-2003 outbreak probably originated from similar animal-to-human transmission, but selection and purification of the animal severe acute respiratory syndrome-like virus appears to have occurred, creating the more virulent severe acute respiratory syndrome-associated coronavirus. Recent studies have documented that severe acute respiratory syndrome-associated coronavirus is primarily transmitted via contact and/or respiratory droplets and that the combination of standard, contact, and droplet precautions is generally effective for its control. It has been shown that severe acute respiratory syndrome-associated coronavirus is typically relatively inefficiently transmitted, with the notable exception of transmission during superspreading events. Insights into the pathogenesis of severe acute respiratory syndrome have been made: one study suggests that human leukocyte antigen HLA-B*4601 is a possible risk factor for more severe disease, while another identifies angiotensin-converting enzyme 2 as a cellular receptor for severe acute respiratory syndrome-associated coronavirus. Promising treatments have been identified, including interferons, an anti-spike monoclonal antibody, and fusion inhibitors. In addition, many promising vaccines are currently in development. SUMMARY: New findings regarding severe acute respiratory syndrome are continuing to be discovered at an unprecedented pace, permitting a better understanding of the disease and enabling better preparation for its possible return.     

A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position

The question whether antidiabetes drugs can cause acute pancreatitis dates back to the 1970s. Recently, old concerns have re‐emerged following claims that use of incretins, a new class of drugs for type 2 diabetes, might increase the relative risk of acute pancreatitis up to 30‐fold. Given that diabetes is per se a potent risk factor for acute pancreatitis and that drug‐related acute pancreatitis is rare and difficult to diagnose, we searched the medical databases for information linking acute pancreatitis and type 2 diabetes drugs. Among the biguanides, both phenformin and metformin (the latter in patients with renal insufficiency) have been cited in case reports as a potential cause of acute pancreatitis. Sulphonylureas, as both entire class and single compound (glibenclamide), have also been found in cohort studies to increase its risk. No direct link was found between pancreatic damage and therapy with metaglinide, acarbose, pramlintide or SGLT‐2 inhibitors. In animal models, thiazolinediones have demonstrated proprieties to attenuate pancreatic damage, opening perspectives for their use in treating acute pancreatitis in humans. Several case reports and the US Food and Drug Administration pharmacovigilance database indicate an association between acute pancreatitis and incretins, dipeptidyl peptidase‐4 (DPP‐4) inhibitors, and GLP‐1 receptor agonists. To date, however, a clear‐cut odds ratio for this association has been reported in only one of eight pharmacoepidemiological studies. Finally, none of the intervention trials investigating these compounds, including two large randomized controlled trials with cardiovascular endpoints, confirmed the purportedly increased risk of acute pancreatitis with incretin use.     

Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia is the major pediatric cancer in developed countries. To date most association studies of acute lymphoblastic leukemia have been based on the candidate gene approach and have evaluated a restricted number of polymorphisms. Such studies have served to highlight difficulties in conducting statistically and methodologically rigorous investigations into acute lymphoblastic leukemia risk. Recent genome-wide association studies of childhood acute lymphoblastic leukemia have provided robust evidence that common variation at four genetic loci confers a modest increase in risk. The accumulated experience to date and relative lack of success of initial efforts to identify novel acute lymphoblastic leukemia predisposition loci emphasize the need for alternative study designs and methods. The International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium includes 12 research groups in Europe, Asia, the Middle East and the Americas engaged in studying the genetics of acute lymphoblastic leukemia. The initial goal of this consortium is to identify and characterize low-penetrance susceptibility variants for acute lymphoblastic leukemia through association-based analyses. Efforts to develop genome-wide association studies of acute lymphoblastic leukemia, in terms of both sample size and single nucleotide polymorphism coverage, and to increase the number of single nucleotide polymorphisms taken forward to large-scale replication should lead to the identification of additional novel risk variants for acute lymphoblastic leukemia. Ethnic differences in the risk of acute lymphoblastic leukemia are well recognized and thus in assessing the interplay between inherited and non-genetic risk factors, analyses using different population cohorts with different incidence rates are likely to be highly informative. Given that the frequency of many acute lymphoblastic leukemia subgroups is small, identifying differential effects will realistically only be possible through multi-center pooled analyses. Here, we review the rationale for identifying genetic risk variants for acute lymphoblastic leukemia and our proposed strategy for establishing the International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium.     

Acute Hepatic Porphyria

The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting.     

Gender differences and the outcome of interventions for acute coronary syndromes

Differences in the overall mortality for acute infarction in women vs men have been appreciated for some time. Some of these differences are based on the age at the time of presentation of women compared with men. Excess mortality in women is most clear at the younger end of the age spectrum. More careful examination of the data has shown differences based on factors such as greater delays in presentation in women, real biases in the types of healthcare provider, and selection of diagnostic and therapeutic interventions for women compared with men. Recently, the mode of presentation has emerged as a major defining point. Women present more frequently with unstable angina or non-Q-wave infarction and have lesser mortality with these syndromes compared with men. Thus, the overall outcomes of acute coronary syndromes vary substantially from the differences in outcome for acute Q-wave infarction alone. New data have emerged regarding differences in treatment outcome for acute infarction. Women have derived lesser benefit from thrombolytic therapy and still respond to percutaneous transluminal coronary angioplasty more favorably than thrombolytic therapy for acute infarction. Women seem to have less benefit from stent use compared with angioplasty alone for acute infarction. Although increasing scrutiny has shed a great deal of light on some of these gender differences in outcomes from acute coronary syndromes, a real difference in mortality for younger women remains unexplained. The basis for real differences in outcome with the use of various therapies for acute infarction, such as thrombolysis and stent use, are also not well elucidated.     

A Protocol for the Emergency Treatment of Acute Asthma in Adults

Despite a greater understanding of the pathogenesis of asthma (1) and an enlarging armamentarium of drugs used to treat it, acute exacerbations remain a frequent cause of visits to hospital emergency rooms. Many different therapies have been utilized to treat acute asthma and in recent years a number of investigators have studied various components of the assessment and treatment of acute attacks (2-6). Although our level of sophistication in approaching asthma has increased, no gold standard has evolved for emergency therapy. To a large degree, the personal preference of the treating physician remains the greatest determinant of therapy for acute exacerbations.     

氧化应激与ALI/ARDS的关系

氧化应激状态系指机体在遭受各种有害刺激时,体内总自由基的生成超过抗氧化体系的防御能力,体内氧化与抗氧化体系的失衡,并倾向于氧化,从而导致机体组织损伤.氧化应激引起的肺组织损伤是ALI/ARDS的一种重要形式,氧化应激失衡可能为ALI/ARDS的发病机制之一.大量动物实验及临床试验证实应用抗氧化治疗可明显改善ALI/ARDS的生理参数,对肺损伤有一定的保护作用.     

Coronary Intervention in Patients With Acute Coronary Syndrome: Does Every Culprit Lesion Require Revascularization?

In patients presenting with acute coronary syndromes, 30–60% of patients have multiple significant coronary lesions. Patients presenting with acute coronary syndrome and multivessel disease have a significant increase in the incidence of major cardiovascular morbidity and mortality when compared with patients who have single-vessel disease. Although great progress has been made to reduce the extent of infarction through effective and rapid reperfusion due to faster time to reperfusion, potent antiplatelets, and antithrombotics, there is not much consensus as to how best to treat multivessel disease in patients presenting with acute coronary syndromes. We present a review of the current body of evidence for safety and efficacy of multivessel revascularization in patients presenting with acute coronary syndromes.     

Mixed acute leukaemias

In recent years immunophenotyping and analysis of clonal rearrangement of immunoglobulin and T-cell antigen receptor genes have proved valuable for the diagnosis and classification of leukaemia. These techniques aid in the assignment of cell lineage in cases of acute leukaemia in which the standard FAB criteria of morphology and cytochemistry do not reveal clear lymphoid or myeloid phenotype. These new techniques have also revealed that the leukaemic blasts in a sizable minority of otherwise typical cases of acute leukaemia express 'inappropriate' lineage-associated markers and have been termed mixed acute leukaemias. The spectrum of characteristics encompassed by mixed acute leukaemias ranges from fairly common cases expressing one or two inappropriate markers to the more extreme, rare cases of acute leukaemia termed 'hybrid' in which a truly scrambled picture is seen. A subgroup of these mixed cases have two distinct populations of blasts, e.g. one lymphoid and the other myeloid. These observations raise a number of issues about the cell of origin of these leukaemias and about the mechanisms controlling the developmental regulation of expression of different lineage-associated markers. In addition, accumulating evidence suggests that inappropriate expression of markers may identify sub-groups of both acute myeloid and lymphoblastic leukaemia with an inferior prognosis.     

Challenges in Acute Ischemic Stroke Clinical Trials

There have been only 3 positive Phase III randomized clinical trials in acute ischemic stroke, all reperfusion therapies (NINDS; PROACT II; ECASS III). The only approved acute stroke therapy is <3-hour IV tPA. Although numerous compounds have shown benefit in animal models of brain infarction, there has never been a positive Phase III randomized clinical trial of a neuroprotectant in acute ischemic stroke. There are many challenges to acute stroke clinical trials but chief among these are the very short therapeutic window (??time is brain??) and the issue of stroke heterogeneity. Stroke is a syndrome and only a very small percentage of all stroke patients present to hospitals in time to consider reperfusion therapy. Many drugs have been rushed to trial prematurely based on inadequate preclinical testing. Many trials have been seriously underpowered due to overly optimistic treatment expectations and the risk of brain hemorrhage has precluded aggressive multimodal treatment strategies. Rather than simply relying on a clock, new imaging methods are being developed to identify patients with ??tissue at risk?? and ??salvageable brain?? regardless of time of stroke onset. The 7 STAIR conferences have been convened to address these and other challenges to acute ischemic stroke trial design and completion.     

Lipid-lowering drugs in lupus: an unexplored therapeutic intervention

Lipid-lowering drugs have been shown to have profound actions beyond modulation of lipid profiles. Statins have been shown to reduce the levels of pro-inflammatory cytokines and markers of acute phase response including C-reactive protein and serum amyloid A. Fibrates have also shown to reduce interleukin-6 levels. Both groups of drugs seem to act through a peroxisomal proliferating activating receptor alpha mechanism to achieve these actions. In lupus, there is profound activation of cytokine production and the acute phase response and a markedly increased risk for the development of atherosclerosis. The role of lipid-lowering drugs in the management of both the acute and chronic sequelae of lupus needs to be explored.     

The haploidentical option for high-risk haematological malignancies

Much progress has been made in the clinical, biological and technical aspects of the T-cell-depleted full-haplotype mismatched transplants for acute leukaemia. Our experience demonstrates that infusing a megadose of extensively T-cell-depleted haematopoietic peripheral blood stem cells after an immuno-myeloablative conditioning regimen in acute leukaemia patients ensures sustained engraftment with minimal GvHD without the need of any post-transplant immunosuppressive treatment. Since our first successful pilot study, our efforts have concentrated on developing new conditioning regimens, optimising the graft processing and improving the post-transplant immunological recovery. The results we have so far achieved in more than 200 high-risk acute leukaemia patients show that haploidentical transplantation is now a clinical reality. Because virtually all patients have a mismatched family member, who is immediately available, mismatched transplantation should be offered as a viable option to high-risk acute leukaemia patients who do not have, or cannot find, a matched donor.     

Chest pain centers: diagnosis of acute coronary syndromes

Chest pain centers in the emergency department have generally been accepted as a safe, cost-effective, and rapid approach to the evaluation, triage, and management of patients with potential acute coronary syndromes. These centers were initially designed to enhance patient care by decreasing time to treatment for acute myocardial infarction (AMI) and rapidly identifying patients with unstable angina. They also included community outreach and educational objectives designed to reduce time from the onset of chest pain to ED presentation. In the past decade, health care financial constraints have created additional impetus to the development of chest pain centers. Cost reduction efforts have occurred to reduce hospitalizations, lengths of stay, and unnecessary treatments and procedures. Practitioners and administrators try to balance these goals with the imperative to provide high-quality patient care. Protocol-driven approaches have been developed for specific disease processes in emergency settings. The chest pain center concept is such an approach for patients with chest pain. Chest pain is the second most common ED presenting complaint and is a symptom related to the leading cause of death in the United States, coronary artery disease (CAD). One third of ED patients with chest pain will eventually have a diagnosis of acute coronary syndrome. Many patients with acute coronary syndromes have atypical presentations that are not diagnosed in the ED with the traditional diagnostic evaluation of a history, physical examination, and 12-lead ECG. If they are not admitted to the hospital for further evaluation, the diagnosis may be missed. The 2% to 5% of AMI patients who are inadvertently released home often have poor outcomes and result in a leading cause of malpractice suits in emergency medicine. More than one half of ED patients with chest pain have clinical findings after their initial evaluation consistent with acute coronary syndromes and are admitted to the hospital. Approximately one half of these patients, after evaluation in the hospital, are found not to have acute coronary syndromes. The cost for these negative inpatient cardiac evaluations has been estimated to be $6 billion in the United States each year. Today, chest pain centers serve as an integral component of many EDs. Their success and safety is the result of a focused, protocol-driven approach directed at the acute coronary syndrome continuum from unstable angina to transmural Q-wave myocardial infarction. New therapies for acute coronary syndromes make ED triage and risk stratification increasingly important. Although different chest pain center protocols have proved effective, all address the diagnosis and rapid treatment of acute myocardial necrosis, rest ischemia, and exercise-induced ischemia. Identifying patients with coronary artery disease in one of these stages in the spectrum of myocardial ischemia is the foundation for a successful chest pain center in the ED.     

Integration of monoclonal antibodies and immunoconjugates into the treatment of acute myeloid leukemia

PURPOSE OF REVIEW: This review addresses use of monoclonal antibodies and immunoconjugates to treat acute myeloid leukemia. RECENT FINDINGS: Monoclonal antibodies used in acute myeloid leukemia have been directed against the antigens CD33, CD45, and CD66. Unconjugated monoclonal antibodies such as lintuzumab have modest activity against overt acute myeloid leukemia but can eliminate minimal residual disease in acute promyelocytic leukemia. Most experience with immunoconjugates is with gemtuzumab ozogamicin, an anti-CD33 monoclonal antibody linked to the potent antitumor antibiotic calicheamicin. Gemtuzumab ozogamicin has shown activity both singly, particularly in acute promyelocytic leukemia, and combined with conventional cytotoxic chemotherapy. Radiolabeled monoclonal antibodies against CD45 and CD66 have also been used to intensify the conditioning regimen before stem cell transplantation. The most promising results were obtained with radiolabeled anti-CD45 antibodies. Antibodies reactive with CD66 have been used to deliver targeted radiation to hematopoietic tissues in patients with advanced myeloid malignancies. SUMMARY: Both unlabeled monoclonal antibodies and immunoconjugates appear to have a limited role if used as single agents to treat acute myeloid leukemia. These agents hold promise as potentially useful additions to conventional therapy, but the optimal dosing and timing remain to be defined.     

Bacterial analysis of infected pancreatic necrosis and its prevention (Symposium 8: Pancreatobiliary infection (IHPBA))

In severe acute pancreatitis, sepsis mainly due to pancreatic or peripancreatic infection have emerged as the most serious complications and now accounts for more than 80% of deaths. Collective review of organisms associated with secondary pancreatic infection in patients with acute pancreatitis has revealed that most of them are intestinal flora. Several experimental studies including ours have revealed that acute pancreatitis promotes bacterial translocation (BT), which in turn leads to infection of the pancreas and septic complications. Prophylactic antibiotics given intravenously have been demonstrated to be beneficial in reducing the rate of pancreatic infection, but their survival benefit remains unclear. We have demonstrated that continuous regional arterial infusion (CRAI) of an antibiotic is more effective than intravenous administration in preventing pancreatic infection and improving survival, in a canine model of acute necrotizing pancreatitis. Our recent experimental study has revealed that CRAI of an antibiotic via the superior mesenteric artery (SMA) is effective in mitigating intestinal mucosal damage and preventing BT in acute pancreatitis, thereby improving survival. BT aggravates pancreatic necrosis and remote organ damage in acute pancreatitis, and SMA infusion of antibiotics is effective in preventing BT and is practical for clinical use.     

Evolving strategies in the management of acute coronary syndromes with oral antiplatelet agents

The treatment of acute coronary syndromes (ACS) is currently undergoing an interesting evolution due to the introduction of some novel antithrombotic drugs. The available evidence on new oral antiplatelet agents can be summarized as follows: (1) the new drugs (prasugrel and ticagrelor) are faster, more potent, and more predictable than clopidogrel, and thus prasugrel or ticagrelor may replace clopidogrel in most patients with ACS; (2) prasugrel seems to have a more pronounced acute effect, especially in patients with acute ST-elevation myocardial infarction (STEMI), and thus prasugrel may be the preferred drug for STEMI, especially for the acute phase; (3) ticagrelor seems to have better secondary preventive effects in the long term, which may be advantageous for patients with acute non-STEMI; and (4) both new drugs have some contraindications or unpleasant side effects and are both substantially more expensive, which may keep a place in therapy for clopidogrel for selected patients.