Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract. While a cure remains elusive, both can be treated with medications that induce and maintain remission....Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract. While a cure remains elusive, both can be treated with medications that induce and maintain remission. With the recent advent of therapies that inhibit tumor necrosis factor (TNF) alpha the overlap in medical therapies for UC and CD has become greater. Although 5-ASA agents have been a mainstay in the treatment of both CD and UC, the data for their efficacy in patients with CD, particularly as maintenance therapy, are equivocal. Antibiotics may have a limited role in the treatment of colonic CD. Steroids continue to be the first choice to treat active disease not responsive to other more conservative therapy; non- systemic steroids such as oral and rectal budesonide for ileal and right-sided CD and distal UC respectively are also effective in mild-moderate disease. 6-mercaptopurine (6-MP) and its prodrug azathioprine are steroid-sparing immunomodulators effective in the maintenance of remission of both CD and UC, while methotrexate may be used in both induction and maintenance of CD. Infliximab and adalimumab are anti-TNF agents approved in the US and Europe for the treatment of Crohn's disease, and infliximab is also approved for the treatment of UC.展开更多
BACKGROUND Hepatitis B virus(HBV) is a cause of hepatocellular carcinoma(HCC). Interestingly, this process is not necessarily mediated through cirrhosis and may in fact involve oncogenic processes. Prior studies have ...BACKGROUND Hepatitis B virus(HBV) is a cause of hepatocellular carcinoma(HCC). Interestingly, this process is not necessarily mediated through cirrhosis and may in fact involve oncogenic processes. Prior studies have suggested specific oncogenic gene expression pathways were affected by viral regulatory proteins. Thus, identifying these genes and associated pathways could highlight predictive factors for HCC transformation and has implications in early diagnosis and treatment.AIM To elucidate HBV oncogenesis in HCC and identify potential therapeutic targets.METHODS We employed our Search, Tag, Analyze, Resource platform to conduct a meta-analysis of public data from National Center for Biotechnology Information’s Gene Expression Omnibus. We performed meta-analysis consisting of 155 tumor samples compared against 185 adjacent nontumor samples and analyzed results with ingenuity pathway analysis.RESULTS Our analysis revealed liver X receptors/retinoid X receptor(RXR) activation and farnesoid X receptor/RXR activation as top canonical pathways amongst others. Top upstream regulators identified included the Ras family gene rab-like protein 6(RABL6). The role of RABL6 in oncogenesis is beginning to unfold but its specific role in HBV-related HCC remains undefined. Our causal analysis suggests RABL6 mediates pathogenesis of HBV-related HCC through promotion of genes related to cell division, epigenetic regulation, and Akt signaling. We conducted survival analysis that demonstrated increased mortality with higher RABL6 expression. Additionally, homeobox A10(HOXA10) was a top upstream regulator and was strongly upregulated in our analysis. HOXA10 has recently been demonstrated to contribute to HCC pathogenesis in vitro. Our causal analysis suggests an in vivo role through downregulation of tumor suppressors and other mechanisms.CONCLUSION This meta-analysis describes possible roles of RABL6 and HOXA10 in the pathogenesis of HBV-related HCC. RABL6 and HOXA10 represent potential therapeutic targets and warrant further investigation.展开更多
AIM: To describe the clinicopathologic features of concurrent polyomavirus nephropathy(PVN) and endarteritis due to rejection in renal allografts.METHODS: We searched our electronic records database for cases with tra...AIM: To describe the clinicopathologic features of concurrent polyomavirus nephropathy(PVN) and endarteritis due to rejection in renal allografts.METHODS: We searched our electronic records database for cases with transplant kidney biopsies demonstrating features of both PVN and acute rejection(AR). PVN was defined by the presence of typical viral cytopathic effect on routine sections and positive polyomavirus SV40 large-T antigen immunohistochemistry. AR was identified by endarteritis(v1 by Banff criteria). All cases were subjected to chart review in order to determine clinical presentation, treatment course and outcomes. Outcomes were recorded with a length of follow-up of at least one year or time to nephrectomy. RESULTS: Of 94 renal allograft recipients who developed PVN over an 11-year period at our institution, we identified 7(7.4%) with viral cytopathic changes, SV40 large T antigen staining, and endarteritis in the same biopsy specimen, indicative of concurrent PVN and AR. Four arose after reduction of immunosuppression(IS)(for treatment of PVN in 3 and tuberculosis in 1), and 3 patients had no decrease of IS before developing simultaneous concurrent disease. Treatment consisted of reduced oral IS and leflunomide for PVN, and antirejection therapy. Three of 4 patients who developed endarteritis in the setting of reduced IS lost their grafts to rejection. All 3 patients with simultaneous PVN and endarteritis cleared viremia and were stable at 1 year of follow up. Patients with endarteritis and PVN arising in a background of reduced IS had more severe rejection and poorer outcome.CONCLUSION: Concurrent PVN and endarteritis may be more frequent than is currently appreciated and may occur with or without prior reduction of IS.展开更多
Staphylococcus aureus has increasingly been recognized as a cause of severe invasive illness. We describe three children who died at our institution after rapidly progressive clinical deterioration from this infection...Staphylococcus aureus has increasingly been recognized as a cause of severe invasive illness. We describe three children who died at our institution after rapidly progressive clinical deterioration from this infection, with necrotizing pneumonia and multiple-organsystem involvement. The identification of bilateral adrenal hemorrhage at autopsy was characteristic of the Waterhouse-Friderichsen syndrome, a constellation of findings usually associated with fulminant meningococcemia. The close genetic relationship among the three responsible isolates of S. aureus, one susceptible to methicillin and two resistant to methicillin, underscores the close relationship between virulent methicillin-suscepti-ble S. aureus and methicillin-resistant S. aureus isolates now circulating in the community.展开更多
Staphylococcus aureus has increasingly been recognized as a cause of severe invasive illness. We describe three children who died at our institution after rapidly progressive clinical deterioration from this infection...Staphylococcus aureus has increasingly been recognized as a cause of severe invasive illness. We describe three children who died at our institution after rapidly progressive clinical deterioration from this infection, with necrotizing pneumonia and multiple-organsystem involvement. The identification of bilateral adrenal hemorrhage at autopsy was characteristic of the Waterhouse-Friderichsen syndrome, a constellation of findings usually associated with fulminant meningococcemia. The close genetic relationship among the three responsible isolates of S. aureus, one susceptible to methicillin and two resistant to methicillin, underscores the close relationship between virulent methicillin-suscepti-ble S. aureus and methicillin-resistant S. aureus isolates now circulating in the community.展开更多
Context: The survival benefit of well-performed cardiopulmonary resuscitation(CPR) is well-documented, but little objective data exist regarding actual CPR quality during cardiac arrest. Recent studies have challenged...Context: The survival benefit of well-performed cardiopulmonary resuscitation(CPR) is well-documented, but little objective data exist regarding actual CPR quality during cardiac arrest. Recent studies have challenged the notion that CPR is uniformly performed according to established international guidelines. Objectives: To measure multiple parameters of in-hospital CPR quality and to determine compliance with published American Heart Association and international guidelines. Design and Setting: A prospective observational study of 67 patients who experienced in-hospital cardiac arrest at the University of Chicago Hospitals, Chicago, Ill, between December 11, 2002, and April 5, 2004. Using a monitor/-defibrillator with novel additional sensing capabilities, the parameters of CPR quality including chest compression rate, compression depth, ventilation rate, and the fraction of arrest time without chest compressions(no-flow fraction) were recorded. Main Outcome Measure: Adherence to American Heart Association and international CPR guidelines. Results: Analysis of the first 5 minutes of each resuscitation by 30-second segments revealed that chest compression rates were less than 90/min in 28.1%of segments. Compression depth was too shallow(defined as< 38 mm) for 37.4%of compressions. Ventilation rates were high, with 60.9%of segments containing a rate of more than 20/min. Additionally, the mean(SD) no-flow fraction was 0.24(0.18). A 10-second pause each minute of arrest would yield a no-flow fraction of 0.17. A total of 27 patients(40.3%) achieved return of spontaneous circulation and 7(10.4%) were discharged from the hospital. Conclusions: In this study of in-hospital cardiac arrest, the quality of multiple parameters of CPR was inconsistent and often did not meet published guideline recommendations, even when performed by well-trained hospital staff. The importance of high-quality CPR suggests the need for rescuer feedback and monitoring of CPR quality during resuscitation efforts.展开更多
Osseous metaplasia in leiomyomas is extremely rare. Here, we report the case of an ossified subcutaneous leiomyoma in a 34-year-old African American man with sickle cell thalassemia who presented with a painful nodule...Osseous metaplasia in leiomyomas is extremely rare. Here, we report the case of an ossified subcutaneous leiomyoma in a 34-year-old African American man with sickle cell thalassemia who presented with a painful nodule of the scapular region, which appeared as a heavily mineralized soft tissue mass on chest radiographs. Histopathologic and immunohistochemical examination of the resected nodule revealed a benign soft tissue leiomyoma composed of intersecting fascicles of spindle cells that strongly expressed smooth muscle actin and caldesmon. Extensive intratumoral calcification and ossification were noticed. Only eight cases of ossified leiomyoma have been reported, of which two arose in the deep soft tissue. Those cases are briefly reviewed and discussed.展开更多
Approximately one third of hepatitis C virus (HCV) genotype 1 patients achieved a sustained virological response (SVR) after 24 weeks of treatment with peginterferon α-2a (40 kd) plus ribavirin in a randomized, multi...Approximately one third of hepatitis C virus (HCV) genotype 1 patients achieved a sustained virological response (SVR) after 24 weeks of treatment with peginterferon α-2a (40 kd) plus ribavirin in a randomized, multinational trial. We aimed to identify factors associated with a rapid virological response (RVR) at week 4 (HCV RNA < 50 IU/mL) and a SVR (HCV RNA < 50 IU/mL at the end of follow-up) in these patients. Stepwise multiple logistic regression analysis was used to explore the prognostic factors for a RVR and SVR in genotype 1 patients treated for 24 weeks. Fifty-one of 216 (24%) genotype 1 patients in the 24-week treatment groups had a RVR. SVR rates were considerably higher in patients without a RVR (89%vs. 19%, respectively). Patients with a baseline HCV RNA of less than 200,000 IU/mL (OR 9.7, 95%CI 4.2-22.5; P < .0001) or 200,000-600,000 IU/mL (OR 3.6, 95%CI 1.5-9.1; P = .0057) were more likely to achieve a RVR than those with HCV RNA greater than 600,000 IU/mL. HCV subtype (1b vs. 1a) was also independently associated with RVR (OR 1.8, 95%CI 0.9-3.7; P = .0954). RVR (OR 23.7 vs. no RVR, 95%CI 9.1-61.7) and baseline HCV RNA less than 200,000 IU/mL (OR 2.7 vs. >600,000 IU/mL, 95%CI 1.1-6.3; P < .026) were significant and independent predictors of SVR in patients treated for 24 weeks. In conclusion, patients infected with HCV genotype 1 and treated with peginterferon α-2a/ ribavirin sustained a RVR 24%of the time. This portends an 89%probability of a SVR after 24 weeks of treatment.展开更多
文摘Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract. While a cure remains elusive, both can be treated with medications that induce and maintain remission. With the recent advent of therapies that inhibit tumor necrosis factor (TNF) alpha the overlap in medical therapies for UC and CD has become greater. Although 5-ASA agents have been a mainstay in the treatment of both CD and UC, the data for their efficacy in patients with CD, particularly as maintenance therapy, are equivocal. Antibiotics may have a limited role in the treatment of colonic CD. Steroids continue to be the first choice to treat active disease not responsive to other more conservative therapy; non- systemic steroids such as oral and rectal budesonide for ileal and right-sided CD and distal UC respectively are also effective in mild-moderate disease. 6-mercaptopurine (6-MP) and its prodrug azathioprine are steroid-sparing immunomodulators effective in the maintenance of remission of both CD and UC, while methotrexate may be used in both induction and maintenance of CD. Infliximab and adalimumab are anti-TNF agents approved in the US and Europe for the treatment of Crohn's disease, and infliximab is also approved for the treatment of UC.
文摘BACKGROUND Hepatitis B virus(HBV) is a cause of hepatocellular carcinoma(HCC). Interestingly, this process is not necessarily mediated through cirrhosis and may in fact involve oncogenic processes. Prior studies have suggested specific oncogenic gene expression pathways were affected by viral regulatory proteins. Thus, identifying these genes and associated pathways could highlight predictive factors for HCC transformation and has implications in early diagnosis and treatment.AIM To elucidate HBV oncogenesis in HCC and identify potential therapeutic targets.METHODS We employed our Search, Tag, Analyze, Resource platform to conduct a meta-analysis of public data from National Center for Biotechnology Information’s Gene Expression Omnibus. We performed meta-analysis consisting of 155 tumor samples compared against 185 adjacent nontumor samples and analyzed results with ingenuity pathway analysis.RESULTS Our analysis revealed liver X receptors/retinoid X receptor(RXR) activation and farnesoid X receptor/RXR activation as top canonical pathways amongst others. Top upstream regulators identified included the Ras family gene rab-like protein 6(RABL6). The role of RABL6 in oncogenesis is beginning to unfold but its specific role in HBV-related HCC remains undefined. Our causal analysis suggests RABL6 mediates pathogenesis of HBV-related HCC through promotion of genes related to cell division, epigenetic regulation, and Akt signaling. We conducted survival analysis that demonstrated increased mortality with higher RABL6 expression. Additionally, homeobox A10(HOXA10) was a top upstream regulator and was strongly upregulated in our analysis. HOXA10 has recently been demonstrated to contribute to HCC pathogenesis in vitro. Our causal analysis suggests an in vivo role through downregulation of tumor suppressors and other mechanisms.CONCLUSION This meta-analysis describes possible roles of RABL6 and HOXA10 in the pathogenesis of HBV-related HCC. RABL6 and HOXA10 represent potential therapeutic targets and warrant further investigation.
文摘AIM: To describe the clinicopathologic features of concurrent polyomavirus nephropathy(PVN) and endarteritis due to rejection in renal allografts.METHODS: We searched our electronic records database for cases with transplant kidney biopsies demonstrating features of both PVN and acute rejection(AR). PVN was defined by the presence of typical viral cytopathic effect on routine sections and positive polyomavirus SV40 large-T antigen immunohistochemistry. AR was identified by endarteritis(v1 by Banff criteria). All cases were subjected to chart review in order to determine clinical presentation, treatment course and outcomes. Outcomes were recorded with a length of follow-up of at least one year or time to nephrectomy. RESULTS: Of 94 renal allograft recipients who developed PVN over an 11-year period at our institution, we identified 7(7.4%) with viral cytopathic changes, SV40 large T antigen staining, and endarteritis in the same biopsy specimen, indicative of concurrent PVN and AR. Four arose after reduction of immunosuppression(IS)(for treatment of PVN in 3 and tuberculosis in 1), and 3 patients had no decrease of IS before developing simultaneous concurrent disease. Treatment consisted of reduced oral IS and leflunomide for PVN, and antirejection therapy. Three of 4 patients who developed endarteritis in the setting of reduced IS lost their grafts to rejection. All 3 patients with simultaneous PVN and endarteritis cleared viremia and were stable at 1 year of follow up. Patients with endarteritis and PVN arising in a background of reduced IS had more severe rejection and poorer outcome.CONCLUSION: Concurrent PVN and endarteritis may be more frequent than is currently appreciated and may occur with or without prior reduction of IS.
文摘Staphylococcus aureus has increasingly been recognized as a cause of severe invasive illness. We describe three children who died at our institution after rapidly progressive clinical deterioration from this infection, with necrotizing pneumonia and multiple-organsystem involvement. The identification of bilateral adrenal hemorrhage at autopsy was characteristic of the Waterhouse-Friderichsen syndrome, a constellation of findings usually associated with fulminant meningococcemia. The close genetic relationship among the three responsible isolates of S. aureus, one susceptible to methicillin and two resistant to methicillin, underscores the close relationship between virulent methicillin-suscepti-ble S. aureus and methicillin-resistant S. aureus isolates now circulating in the community.
文摘Staphylococcus aureus has increasingly been recognized as a cause of severe invasive illness. We describe three children who died at our institution after rapidly progressive clinical deterioration from this infection, with necrotizing pneumonia and multiple-organsystem involvement. The identification of bilateral adrenal hemorrhage at autopsy was characteristic of the Waterhouse-Friderichsen syndrome, a constellation of findings usually associated with fulminant meningococcemia. The close genetic relationship among the three responsible isolates of S. aureus, one susceptible to methicillin and two resistant to methicillin, underscores the close relationship between virulent methicillin-suscepti-ble S. aureus and methicillin-resistant S. aureus isolates now circulating in the community.
文摘Context: The survival benefit of well-performed cardiopulmonary resuscitation(CPR) is well-documented, but little objective data exist regarding actual CPR quality during cardiac arrest. Recent studies have challenged the notion that CPR is uniformly performed according to established international guidelines. Objectives: To measure multiple parameters of in-hospital CPR quality and to determine compliance with published American Heart Association and international guidelines. Design and Setting: A prospective observational study of 67 patients who experienced in-hospital cardiac arrest at the University of Chicago Hospitals, Chicago, Ill, between December 11, 2002, and April 5, 2004. Using a monitor/-defibrillator with novel additional sensing capabilities, the parameters of CPR quality including chest compression rate, compression depth, ventilation rate, and the fraction of arrest time without chest compressions(no-flow fraction) were recorded. Main Outcome Measure: Adherence to American Heart Association and international CPR guidelines. Results: Analysis of the first 5 minutes of each resuscitation by 30-second segments revealed that chest compression rates were less than 90/min in 28.1%of segments. Compression depth was too shallow(defined as< 38 mm) for 37.4%of compressions. Ventilation rates were high, with 60.9%of segments containing a rate of more than 20/min. Additionally, the mean(SD) no-flow fraction was 0.24(0.18). A 10-second pause each minute of arrest would yield a no-flow fraction of 0.17. A total of 27 patients(40.3%) achieved return of spontaneous circulation and 7(10.4%) were discharged from the hospital. Conclusions: In this study of in-hospital cardiac arrest, the quality of multiple parameters of CPR was inconsistent and often did not meet published guideline recommendations, even when performed by well-trained hospital staff. The importance of high-quality CPR suggests the need for rescuer feedback and monitoring of CPR quality during resuscitation efforts.
文摘Osseous metaplasia in leiomyomas is extremely rare. Here, we report the case of an ossified subcutaneous leiomyoma in a 34-year-old African American man with sickle cell thalassemia who presented with a painful nodule of the scapular region, which appeared as a heavily mineralized soft tissue mass on chest radiographs. Histopathologic and immunohistochemical examination of the resected nodule revealed a benign soft tissue leiomyoma composed of intersecting fascicles of spindle cells that strongly expressed smooth muscle actin and caldesmon. Extensive intratumoral calcification and ossification were noticed. Only eight cases of ossified leiomyoma have been reported, of which two arose in the deep soft tissue. Those cases are briefly reviewed and discussed.
文摘Approximately one third of hepatitis C virus (HCV) genotype 1 patients achieved a sustained virological response (SVR) after 24 weeks of treatment with peginterferon α-2a (40 kd) plus ribavirin in a randomized, multinational trial. We aimed to identify factors associated with a rapid virological response (RVR) at week 4 (HCV RNA < 50 IU/mL) and a SVR (HCV RNA < 50 IU/mL at the end of follow-up) in these patients. Stepwise multiple logistic regression analysis was used to explore the prognostic factors for a RVR and SVR in genotype 1 patients treated for 24 weeks. Fifty-one of 216 (24%) genotype 1 patients in the 24-week treatment groups had a RVR. SVR rates were considerably higher in patients without a RVR (89%vs. 19%, respectively). Patients with a baseline HCV RNA of less than 200,000 IU/mL (OR 9.7, 95%CI 4.2-22.5; P < .0001) or 200,000-600,000 IU/mL (OR 3.6, 95%CI 1.5-9.1; P = .0057) were more likely to achieve a RVR than those with HCV RNA greater than 600,000 IU/mL. HCV subtype (1b vs. 1a) was also independently associated with RVR (OR 1.8, 95%CI 0.9-3.7; P = .0954). RVR (OR 23.7 vs. no RVR, 95%CI 9.1-61.7) and baseline HCV RNA less than 200,000 IU/mL (OR 2.7 vs. >600,000 IU/mL, 95%CI 1.1-6.3; P < .026) were significant and independent predictors of SVR in patients treated for 24 weeks. In conclusion, patients infected with HCV genotype 1 and treated with peginterferon α-2a/ ribavirin sustained a RVR 24%of the time. This portends an 89%probability of a SVR after 24 weeks of treatment.