Recently Graduated Medical Students Lack Exposure to and Comfort with Chronic Liver Diseases

Digestive Diseases and Sciences - The prevalence of chronic liver disease (CLD) is rising, but it remains unclear if medical school curricula are emphasizing CLD to reflect its growing...     

Exogenous and Endogenous Triggers Differentially Stimulate Pigr Expression and Antibacterial Secretory Immunity in the Murine Respiratory Tract

Purpose

Transport of secretory immunoglobulin A (SIgA) through the airway epithelial cell barrier into the mucosal lumen by the polymeric immunoglobulin receptor (pIgR) is an important mechanism of respiratory mucosal host defense. Identification of immunomodulating substances that regulate secretory immunity might have therapeutic implications with regard to an improved immune exclusion.

Thus, we sought to analyze secretory immunity under homeostatic and immunomodulating conditions in different compartments of the murine upper and lower respiratory tract (URT&LRT).

Methods

Pigr gene expression in lung, trachea, and nasal-associated lymphoid tissue (NALT) of germ-free mice, specific pathogen-free mice, mice with an undefined microbiome, as well as LPS- and IFN-γ-treated mice was determined by quantitative real-time PCR. IgA levels in bronchoalveolar lavage (BAL), nasal lavage (NAL), and serum were determined by ELISA. LPS- and IFN-γ-treated mice were colonized with Streptococcus pneumoniae and bacterial CFUs were determined in URT and LRT.

Results

Respiratory Pigr expression and IgA levels were dependent on the degree of exposure to environmental microbial stimuli. While immunostimulation with LPS and IFN-γ differentially impacts respiratory Pigr expression and IgA in URT vs. LRT, only prophylactic IFN-γ treatment reduces nasal colonization with S. pneumoniae.

Conclusion

Airway-associated secretory immunity can be partly modulated by exposure to microbial ligands and proinflammatory stimuli. Prophylactic IFN-γ-treatment modestly improves antibacterial immunity in the URT, but this does not appear to be mediated by SIgA or pIgR.

     

Identifying Patients with Group 3 Pulmonary Hypertension Associated with COPD or ILD Using an Administrative Claims Database

Lung - Group 3 pulmonary hypertension (PH) describes a subpopulation of patients with PH due to chronic lung disease and/or hypoxia, with chronic obstructive pulmonary disease (COPD) and...     

Examination of anticoagulation prescription among elderly patients with atrial fibrillation after in-hospital fall

Journal of Thrombosis and Thrombolysis - Mechanical fall is common among elders and has been associated with a lack of anticoagulant therapy among patients with atrial fibrillation (AF). However,...     

Is Frailty a Predictor of Outcomes in Elderly Inpatients with Acute Kidney Injury? A Prospective Cohort Study

Background

Frailty and acute kidney injury are independently associated with an increased risk of morbidity and mortality. The degree of frailty can be assessed by the Clinical Frailty Score (CFS). This study assessed whether an individual's CFS was associated with acute kidney injury in acute elderly medical admissions and recorded the short-term outcomes.

Self-expandable metallic stents for malignant duodenal obstruction caused by biliary tract cancer

BACKGROUND: Malignant duodenal obstruction is a common event in patients with advanced biliary tract cancer. Because bypass surgery is accompanied by significant morbidity, self-expandable metallic stents have emerged as a possible alternative for palliation. METHODS: Twenty patients with biliary tract cancer (7 gallbladder, 13 Klatskin tumors) and duodenal obstruction were treated with metallic stents at a single institution between 1999 and 2001. Survival, morbidity, and stent function were studied prospectively. The ability to eat was assessed by using a scoring system. RESULTS: Stent placement was technically successful in all patients. An additional stent was required in 6 cases (4 occlusions, 2 dislocations). Median survival was 20.5 weeks; there was no treatment-related death. Twenty-eight biliary stent exchanges were performed in 13 (65%) patients. Erosive reflux esophagitis improved in 11 of 12 (92%) cases. After 4 weeks, all 17 surviving patients tolerated soft or solid food, whereas 13 of 17 (77%) tolerated a more solid diet (p < 0.001, gastric outlet obstruction scoring system). Twelve of 17 (71%) patients gained a median of 1.5 kg of body weight (p = 0.001). The median Karnofsky scale increased from 50% to 60% in 13 of 17 (77%) patients. CONCLUSIONS: Self-expandable metallic stents are a safe, efficacious, and minimally invasive treatment option for palliation of patients with duodenal obstruction from biliary tract cancer. Technical complications can be managed endoscopically and the bile duct remains accessible for endoluminal treatment.     

Selective targeted delivery of TNFalpha to tumor blood vessels

We sought to enhance the selective toxicity of tumor necrosis factor alpha (TNFalpha) to permit its systemic use in cancer therapy. Because ligand-targeted therapeutics have proven successful in improving the selective toxicity of drugs, we prepared a fusion protein (L19mTNFalpha) composed of mouse TNFalpha and a high-affinity antibody fragment (L19 scFv) to the extradomain B (ED-B) domain of fibronectin, a marker of angiogenesis. L19mTNFalpha was expressed in mammalian cells, purified, and characterized. L19mTNFalpha was an immunoreactive and biologically active homotrimer. Radiolabeled L19mTNFalpha selectively targeted tumor neovasculature in tumor-bearing mice, where it accumulated selectively and persistently (tumor-to-blood ratio of the percentage of injected dose per gram [%ID/g] of 700, 48 hours from injection). L19mTNFalpha showed a greater anticancer therapeutic activity than both mTNFalpha and TN11mTNFalpha, a control fusion protein in which an antibody fragment, irrelevant in the tumor model used, substituted for L19. This activity was further dramatically enhanced by its combination with melphalan or the recently reported fusion protein L19-IL2. In conclusion, L19mTNFalpha allows concentrating therapeutically active doses of TNFalpha at the tumor level, thus opening new possibilities for the systemic use of TNFalpha in cancer therapy.     

Treatment of renal diseases with plasma exchange: a single center experience

Over the last decades, plasma exchange (PE) has been applied in the treatment of over 150 different diseases including nephrological, hematological, neurological, and rheumatological. Clinical benefit has been demonstrated in only about 40 of them and the best results were achieved in diseases with pathogenic autoimmune mechanisms. We used PE most frequently in patients with immune and autoimmune nephropathies aiming to decrease pathologically elevated antibody levels, autoantibodies and immune complexes. PE was applied in 40 patients with chronic glomerulonephritis, 29 patients with lupus nephritis, and 9 patients with Schoenlein‐Henoch nephritis. After 3 to 4 PE sessions, continuous immunosuppressive drug therapy was initiated. Significant reduction of antibody titers and immune complexes was achieved. PE was also applied in 45 plasmacytoma patients with nephropathy to reduce plasma viscosity and slow down the progression of myeloma nephropathy. The result was a significant reduction of pathologically elevated plasma viscosity and a detoxification effect. In our clinic plasma exchange procedures were performed by either centrifugal method with Haemonetics M‐30 device or by plasma filtration. An average of 1316 mL plasma was removed during a PE session. For substitution purposes donor plasma and saline solutions were used. Clinical remission was achieved in 61.3% of all patients without slowing the progression of renal failure, however.