New therapeutic approaches to hepatitis C virus

Year 201X will see a huge battle against hepatitis C virus (HCV) infection. HCV, a leading cause of end stage diseases and hepatocellular malignancies, is a negative legacy of the past in many regions worldwide, and has long been refractory to conventional treatments. The most effective peginterferons and ribavirin-based antiviral therapies can eliminate the virus in only half of patients treated, and the treatments are often poorly tolerated. Recently, the development of an HCV cell culture system has become a turning point of basic research. At present, novel therapeutic agents with different mechanisms of action are under development or on clinical trials. Some of these drugs have been proven to be effective when used with the conventional treatments, and may constitute antiviral therapies without being used in combination with interferons. This article reviews the current status of preclinical drug development, ongoing clinical trials, and near future perspectives in the field of HCV therapeutics.     

Bacteriology of hospital-acquired pneumonia

Hospital-acquired pneumonia was studied prospectively for 3 1/2 years in a 549-bed facility with acute medical-surgical care wards, convalescent wards, and a chronic care unit. Bacteriological studies were limited to transtracheal aspirates, pleural fluid, and blood cultures. The predominant isolates in 159 patients were gram-negative bacilli (47%), anaerobic bacteria (35%), Staphylococcus aureus (31%), and Streptococcus pneumoniae (26%). Nearly half of all specimens yielded a polymicrobial flora with more than one potential pathogen. Distribution of pathogens was similar with analysis of all patients, including patients with a monomicrobial infection and patients with bacteremic pneumonia. The prevalence of cases and distribution of bacteria were similar for patients located on acute medical-surgical wards and those in the nursing home care unit. Nosocomial pneumonia was judged directly responsible for lethal outcome in 19% of patients and a contributing factor to death in another 13%.     

医疗保健相关性肺炎的经验性治疗

医疗保健相关性肺炎(HCAP)是美国胸科学会与感染病学会(ATS/IDSA)2005年发布的成人医院获得性肺炎(HAP)、呼吸机相关性肺炎(VAP)和医疗保健相关性肺炎治疗指南中提出的新概念。本文主要从治疗场所的选择、治疗策略以及初始经验性抗菌药物选择等方面简要综述了HCAP的经验性治疗推荐,并介绍几种可能会成为治疗HCAP的新选择的抗菌药物,以期为临床医生治疗HCAP患者提供有益的借鉴。     

New therapeutic approaches to treat medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) accounts for up to 8% of all thyroid cancers. Although primary surgery is curative in the vast majority of patients treated at an early stage, disease can persist or recur with deleterious effects on quality of life. Local and distant metastases can occur and are the major causes of mortality. Reoperation, embolization, and perhaps radiotherapy can improve the outcome for some patients who are not cured by primary surgery, but there is a need for novel treatments. No comprehensive clinical trial data are available on conventional cytotoxic agents for the treatment of MTC. Patients with distant metastases, in particular, might benefit from several novel compounds directed against angiogenesis and molecular targets in tumor cells, such as products of the proto-oncogene RET and mutants of it, and other signaling components. Well-conducted clinical trials are needed to assess and optimize these treatment strategies, and this article outlines how such trials should be conducted. Although RET mutations are common in hereditary MTC and can occur in some cases of sporadic MTC, knowledge of other molecular defects associated with the development of MTC should reveal new targets for therapy.     

New diagnostic approaches to the hospitalized patient with pneumonia

The accurate diagnosis of pneumonia remains a formidable challenge in clinical medicine. The use of sputum, blood, and pleural fluid cultures provides a diagnosis in less than 50% of patients. A number of invasive techniques have recently been applied to the diagnosis of pneumonia. The methods are uniformly designed to separate upper respiratory saprophytic bacterial populations from the organisms responsible for the lower respiratory infection. Preeminent among these techniques is the use of fiberoptic bronchoscopy coupled with quantitative bacterial culture and immunofluorescence demonstration of antibody-coated bacteria. The methodology and results of this technique are described in detail in this paper. Recent clinical experience using transtracheal aspiration, percutaneous needle aspiration of the lung, and open lung biopsy are also reviewed.     

New therapeutic approaches for spondyloarthritis

PURPOSE OF REVIEW: Tumor necrosis factor alpha antagonists are effective for signs and symptoms of ankylosing spondylitis. Recent studies have evaluated the efficacy of these agents for structural disease modification. We critically review recent radiographic data suggesting that tumor necrosis factor alpha inhibition may have structure-modifying effects in ankylosing spondylitis, and may thereby alter the disease course. RECENT FINDINGS: Recent studies employing MRI suggest that therapy with tumor necrosis factor alpha antagonists significantly reduces spinal inflammation in active ankylosing spondylitis when compared to placebo; there was no comparable improvement in the severity of chronic stigmata, such as syndesmyophytes and vertebral bridging. These studies were of relatively short duration and small size. SUMMARY: Despite insufficient evidence to conclude definitively that tumor necrosis factor alpha-antagonist therapy provides durable and effective structure modification in ankylosing spondylitis, the data strongly suggest a benefit, at least in the short term. In the future, MRI data coupled with clinical outcomes in larger cohorts followed for longer durations may result in a paradigm shift for ankylosing spondylitis treatment similar to that undergone for rheumatoid arthritis, where patients with ankylosing spondylitis are offered therapy early in the disease course to arrest and prevent structural disease progression.     

Antimicrobial treatment of hospital-acquired pneumonia

This article highlights the importance of providing adequate empirical antibiotic therapy for hospital-acquired pneumonia and avoiding the excessive use of antibiotics. To meet these goals, a strategy for the management of suspected ventilator-associated pneumonia should include obtaining reliable pulmonary specimens for direct microscope examination and cultures before new antibiotics are administered.     

Antimicrobial treatment of hospital-acquired pneumonia

Rapid identification of infected patients and accurate selection of antimicrobial agents for initial treatment of hospital-acquired pneumonia represent important clinical goals, because it seems that better treatment of this infection might have a major impact on hospital-associated mortality and morbidity. Persistently high mortalities for pneumonia in the critical care unit argue, however, for a continued reassessment of the current modalities of therapy and definition of better protocols. More active and less toxic antibacterial agents are still needed. It should be emphasized that in the event that one or several specific etiologic agents are identified by a reliable technique, the choice of antimicrobial drugs is much easier, because the optimal treatment may be selected in light of the susceptibility pattern of the causative pathogens without resorting to broad-spectrum drugs or risking inappropriate treatment. Great efforts should be placed to obtain reliable pulmonary specimens for direct microscopic examination and cultures in each patient clinically suspected of having developed nosocomial pneumonia before new antibiotics are administered.     

Antibacterial therapy of hospital-acquired pneumonia

Antibacterial therapy of hospital-acquired pneumonia
The committee for The Japanese Respiratory Society guidelines in management of respiratory infections. Respirology 2004; 9: S16–S24     

Nonpharmacological prevention of hospital-acquired pneumonia

Hospital-acquired pneumonia (HAP) is the most common nosocomial infection occurring among mechanically ventilated patients. The benefits associated with the systematic prevention of HAP include fewer infections with high-risk antibiotic-resistant bacteria, lower rates of hospital mortality, reduced medical care costs, and shorter hospital lengths of stay. Unfortunately, many hospitals do not have an organized approach to the prevention of HAP. This review will describe the nonpharmacological approaches available for the prevention of HAP. It should help clinicians to design their own strategies for the prevention of this important hospital-acquired infection.     

New therapeutic approaches in pulmonary embolism

Pulmonary embolism as a part of venous thromboembolic disease has a broad spectrum of clinical presentations from minimal disease to life-threatening right heart failure. Therapy has to be guided by the risk associated with the individual clinical state of the patient. As long as hemodynamics are entirely stable, anticoagulation is given in order to prevent early or late recurrence, thereby allowing for endogeneous thrombolysis and recovery. In hemodynamically instable patients, i.e. patients under cardiopulmonary resuscitation or in shock, there is the need for a rapid reduction of thrombus mass in order to restore right ventricular function. Systemic thrombolysis is the most feasible modality to reduce the thrombus burden of the pulmonary circulation in the short term. For hemodynamically stable patients with right ventricular dysfunction as assessed by echocardiography, there is still some controversy as to whether thrombolysis improves the long-term outcome. At the least, thrombolysis may positively modify the short-term course of acute disease in patients with an extremely low risk of bleeding. When the acute phase has been overcome, secondary prophylaxis with vitamin K antagonists has to be given. The duration of secondary prophylaxis requires an individual assessment of both the risk of recurrence and the risk of bleeding. In the near future, new anticoagulant drugs such as direct thrombin and factor Xa inhibitors will offer new treatment modalities for the acute phase as well as for secondary prophylaxis.