As the number of patients receiving total joint replacements continues to rise,considerable attention has been directed towards the early detection and prevention of postoperative complications.While D-dimer has long ...As the number of patients receiving total joint replacements continues to rise,considerable attention has been directed towards the early detection and prevention of postoperative complications.While D-dimer has long been studied as a diagnostic tool in venous thromboembolism(VTE),this assay has recently received considerable attention in the diagnosis of periprosthetic joint infection(PJI).D-dimer values are substantially elevated in the acute postoperative period after total joint arthroplasty,with levels often exceeding the standard institutional cutoff for VTE(500µg/L).The utility of D-dimer in detecting VTE after total joint replacement is currently limited,and more research to assess its value in the setting of contemporary prophylaxis protocols is warranted.Recent literature supports D-dimer as a good to excellent biomarker for the diagnosis of chronic PJI,especially when using serum sample technique.Providers should exercise caution when interpreting D-dimer levels in patients with inflammatory and hypercoagulability disorders,as the diagnostic value is decreased.The updated 2018 Musculoskeletal Infection Society criteria,which includes D-dimer levels>860µg/L as a minor criterion,may be the most accurate for diagnosing chronic PJI to date.Larger prospective trials with transparent lab testing protocols are needed to establish best assay practices and optimal cutoff values for D-dimer in the diagnosis of PJI.This review summarizes the most current literature on the value of D-dimer in total joint arthroplasty and elucidates areas for future progress.展开更多
AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in...AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice. METHODS: Mice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX) inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion. RESULTS: A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-α levels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure. CONCLUSION: Allopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generationof superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.展开更多
Background and Objective Lung cancer has the fastest increasing rate of morbidity and mortality all over the world and appears to be one of the most dangerous malignant tumors
Background and objective Lung cancer has not only become the most frequent malignant cancer which is increasing fastest among all the tumors, but also become the rst killer
Abdominal pain with elevated transaminases from inferior vena cava(IVC) obstruction is a relatively common reason for referral and further workup by a hepatologist. The differential for the cause of IVC obstruction is...Abdominal pain with elevated transaminases from inferior vena cava(IVC) obstruction is a relatively common reason for referral and further workup by a hepatologist. The differential for the cause of IVC obstruction is extensive, and the most common etiologies include clotting disorders or recent trauma. In some situations the common etiologies have been ruled out, and the underlying process for the patient's symptoms is still not explained. We present one unique case of abdominal pain and hepatomegaly secondary to IVC constriction from extrinsic compression of the diaphragm. Based on this patient's presentation, we urge that physicians be cognizant of the IVC diameter and consider extrinsic compression as a contributor to the patient's symptoms. If IVC compression from the diaphragm is confirmed, early referral to vascular surgery is strongly advised for further surgical intervention.展开更多
Near zero stroke rates can be achieved in carotid endarterectomy (CEA) surgery with selective shunting and electrophysiological neuromonitoring.though false negative rates as high as 40% have been reported.We sought...Near zero stroke rates can be achieved in carotid endarterectomy (CEA) surgery with selective shunting and electrophysiological neuromonitoring.though false negative rates as high as 40% have been reported.We sought to determine if improved training for interpretation of the monitoring signals can advance the efficacy of selective shunting with electrophysiological monitoring across multiple centers,and determine if other factors could contribute to the differences in reports.Processed and raw beta band (12.5-30 Hz) electroencephalogram (EEG) and median and tibial nerve somatosensory evoked potentials (SSEP) were monitored in 668 CEA cases at six surgical centers.A decrease in amplitude of 50% or more in any EEG or SSEP channel was the criteria for shunting or initiating a neuroprotective protocol.A reduction of 50% or greater in the beta band of the EEG or amplitude of the SSEP was observed in 150 cases.No patient showed signs of a cerebral infarct after surgery.Selective shunting based on EEG and SSEP monitoring can reduce CEA intraoperative stroke rate to a near zero level if trained personnel adopted standardized protocols.We also found that the rapid administration of a protective stroke protocol by attending anesthesiologists was an important aspect of this success rate.展开更多
Purpose: To investigate the efficacy of a new algorithm to increase the volume of tissue ablation via gradual ramp-up of power using an internally cooled electrode for ablating hepatomas 3 cm or less. Materials and Me...Purpose: To investigate the efficacy of a new algorithm to increase the volume of tissue ablation via gradual ramp-up of power using an internally cooled electrode for ablating hepatomas 3 cm or less. Materials and Methods: 44 patients with 62 hepatomas were treated from March 4, 2004 to May 24, 2009. Ablation with a gradual ramp-up of power was performed using a single needle with an internally cooled electrode. Evaluation for tumor response was performed with 4-phase CT at 24 hours and 3 months. All immediate and follow-up complications were recorded. Results: Complete tumor ablation was achieved in 86%. The ablation volumes were 16 cm3 +/- 12 cm3 for tumors 3 +/- 12 cm3 for tumors 2 - 3 cm. Out of 68 total ablation sessions, there were 2 major complications (pleural effusions) requiring intervention (thoracentesis). Conclusion: Compared with existing techniques using a constant full-power setting, ablation of small hepatomas using an algorithm of gradual ramp-up of power provides comparable rate of complete tumor ablation, adequate ablation volumes, and a low rate of complications that require treatment.展开更多
While advanced technology,increased medical knowledge and improved surgical technique has improved patient outcomes in total joint arthroplasty,prosthetic joint infection still remains one of the leading causes of inc...While advanced technology,increased medical knowledge and improved surgical technique has improved patient outcomes in total joint arthroplasty,prosthetic joint infection still remains one of the leading causes of increased healthcare costs,medical resources and societal burdens in orthopaedic care.Two stage arthroplasty revision remains the gold standard for treatment of prosthetic joint infection.Proponents of single stage revision arthroplasty for infection argue that it results in lower healthcare costs while improving patient reported functional outcomes and with equivalent success rates.Here we review the history of single stage revision arthroplasty,discuss the key principles,highlight the indications and contraindications,and review the reported outcomes with a focus on future developments of single stage revision arthroplasty for hip and knee periprosthetic joint infections.展开更多
Background: We hypothesized: 1) resected pulmonary typical carcinoid (TC) will show a favorable clinical pattern compared to other bronchopulmonary neuroendocrine tumors (BPNETs);and 2) Atypical carcinoid (AC) and lar...Background: We hypothesized: 1) resected pulmonary typical carcinoid (TC) will show a favorable clinical pattern compared to other bronchopulmonary neuroendocrine tumors (BPNETs);and 2) Atypical carcinoid (AC) and large-cell neuroendocrine carcinoma (LCNEC) patients will have similar outcomes. Methods: The Surveillance Epidemiology and End Result database was queried to compare demographics and tumor specific variables in patients undergoing resection for TC, AC, LCNEC and small cell lung cancer (SCLC) from 2001 to 2006. Results: Similar to LCNEC, AC patients had greater incidence of histologic positive lymph nodes compared to TC (P < 0.001). Survival analysis showed a mean survival of 40.0 ± 1.9 months for SCLC, 46.2 ± 2.2 months for LCNEC, 58.3 ± 2.3 months for AC, and 70.2 ± 0.2 months for TC tumors. TC patients demonstrated favorable survival, and SCLC patients poorer survival, compared to AC and LNEC patients (P < 0.01). Conclusion: AC tumors are a BPNET histology that exhibits clinical behavior distinct from TC. AC tumors should be staged, and treated with stage appropriate therapeutic strategies similar to other non-small cell lung cancers.展开更多
Hepatic fibrosis is a wound healing response, involving pathways of inflammation and fibrogenesis. In response to various insults, such as alcohol, ischemia, viral agents, and medications or hepatotoxins, hepatocyte d...Hepatic fibrosis is a wound healing response, involving pathways of inflammation and fibrogenesis. In response to various insults, such as alcohol, ischemia, viral agents, and medications or hepatotoxins, hepatocyte damage will cause the release of cytokines and other soluble factors by Kupffer cells and other cell types in the liver. These factors lead to activation of hepatic stellate cells, which synthesize large amounts of extracellular matrix components. With chronic injury and fibrosis, liver architecture and metabolism are disrupted, eventually manifesting as cirrhosis and its complications. In addition to eliminating etiology, such as antiviral therapy and pharmacological intervention, it is encouraging that novel strategies are being developed to directly address hepatic injury and fibrosis at the subcellular and molecular levels. With improvement in understanding these mechanisms and pathways, key steps in injury, signaling, activation, and gene expression are being targeted by molecular modalities and other molecular or gene therapy approaches. This article intends to provide an update in terms of the current status of molecular therapy for hepatic injury and fibrosis and how far we are from clinical utilization of these new therapeutic modalities.展开更多
AIM:To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease(WD)patients.METHODS:We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent mu...AIM:To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease(WD)patients.METHODS:We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent multiple follow-up liver biopsies.Demographic,clinical and laboratory data were gathered and all patients underwent an initial biopsy and at least one repeat biopsy.RESULTS:Time to repeat biopsy ranged from 2 to 12 years.Six patients(non-progressors)showed stable hepatic histology or improvement.In one case,we observed improvement of fibrosis from stage 2 to 0.Six patients(progressors)had worsening of fibrosis.There was no significant correlation between the histological findings and serum aminotransferases or copper me-tabolism parameters.The hepatic copper concentration reached normal levels in only two patients:one from the non-progressors and one from the progressors group.The estimated rate of progression of hepatic fibrosis in the entire group was 0 units per year in the time frame between the first and the second liver biopsy(4 years),and 0.25 between the second and the third(3 years).In the progressors group,the rate of progression of liver fibrosis was estimated at 0.11 fibrosis units per year between the first and second biopsy and,0.6 fibrosis units between the second and third biopsy.CONCLUSION:The inability of clinical tools to detect fibrosis progression in WD suggests that a liver biopsy with hepatic copper quantification every 3 years should be considered.展开更多
Laparoscopic liver resection (LLR) for the treatment of benign and malignant liver lesions is often performed at specialized centers. Technological advances, such as laparoscopic ultrasonography and electrosurgical to...Laparoscopic liver resection (LLR) for the treatment of benign and malignant liver lesions is often performed at specialized centers. Technological advances, such as laparoscopic ultrasonography and electrosurgical tools, have afforded surgeons simultaneous improvements in surgical technique. The utilization of minimally invasive techniques for liver resection has been reported to reduce operative time, decrease blood loss, and shorten length of hospital stay with equivalent postoperative mortality and morbidity rates compared to open liver resection (OLR). Non-anatomic liver resection and left lateral sectionectomy are now routinely performed laparoscopically at many institutions. Furthermore, major hepatic resections are performed by pure laparoscopy, hand-assisted technique, and the hybrid method. In addition, robotic surgery and single port surgery are revealing early promising results. The consensus recommendation for the treatment of benign liver disease and malignant lesions remains unchanged when considering a laparoscopic approach, except when comorbidities and anatomic limitations of the liver lesion preclude this technique. Disease free and survival rates after LLR for hepatocellular carcinoma and metastatic colon cancer correspond to OLR. Patient selection is a significant factor for these favorable outcomes. The limitations include LLR of superior and posterior liver lesions; however, adjustments in technique may now consider a laparoscopic approach as a viable option. As growing data continue to reveal the feasibility and efficacy of laparoscopic liver surgery, this skill is increasingly being adopted by hepatobiliary surgeons. Although the full scope of laparoscopic liver surgery remains infrequently used by many general surgeons, this technique will become a standard in the treatment of liver diseases as studies continue to show favorable outcomes.展开更多
Endoscopic ultrasound(EUS)is a minimally invasive diagnostic and therapeutic modality with a number of established as well as evolving uses in patients with chronic liver disease.Compared to other diagnostic tools suc...Endoscopic ultrasound(EUS)is a minimally invasive diagnostic and therapeutic modality with a number of established as well as evolving uses in patients with chronic liver disease.Compared to other diagnostic tools such as cross-sectional imaging or conventional endoscopy,EUS has been shown to increase diagnostic sensitivity and therapeutic success for many clinical scenarios and applications with a low rate of adverse events.In this review,we discuss and focus on the current and growing role of EUS in the evaluation and/or treatment of hepatobiliary masses,hepatic parenchymal disease,portal hypertension,esophageal and other varices,and indeterminate biliary strictures.展开更多
Objective: To evaluate the effectiveness of Shenqi Fuzheng Injection (参芪扶正注射液, SFI) combined with chemotherapy for advanced gastric cancer. Methods: Randomized controlled trials (RCTs) from 10 databases w...Objective: To evaluate the effectiveness of Shenqi Fuzheng Injection (参芪扶正注射液, SFI) combined with chemotherapy for advanced gastric cancer. Methods: Randomized controlled trials (RCTs) from 10 databases were searched for this meta-analysis till December 31, 2012 without language restriction. Grey literature and potential unpublished literature was also searched. The key search terms were "chemotherapy", "Shenqi Fuzheng Injection" and "advanced gastric cancer". Criteria were built to select these clinical trials, in which SFI combined with chemotherapy was compared with chemotherapy alone for advanced gastric cancer. The methodological quality of each RCT was assessed using the Cochrane risk of bias tool. RevMan 5.1 software was applied for data analyses. Results: Thirteen RCTs involving 860 patients met the selection criteria (all articles were from Chinese databases). The meta-analysis showed positive results for the use of SFI combined with chemotherapy according to quality of life in terms of the scores when compared with chemotherapy alone. Positive results were also obtained for the combination treatment, in terms of complete remission and partial remission efficacy rate, body weight and decreased adverse events including nausea and vomiting at grade 3-4, oral mucositis at grade 1-2, leucopenia at grade 3-4, and myelo-suppression at grade 1-2. Conclusions: This systematic review found encouraging albeit limited evidence for SFI combined with chemotherapy. However, to obtain stronger evidence without the drawbacks of trial design and the quality of studies, we recommend comparative effectiveness researches to test the effectiveness of combination treatment.展开更多
We demonstrate improved peptide linkers which allow both conjugation to biomolecules such as DNA and self-assembly with luminescent semiconductor quantum dots.A hexahistidine peptidyl sequence was generated by standar...We demonstrate improved peptide linkers which allow both conjugation to biomolecules such as DNA and self-assembly with luminescent semiconductor quantum dots.A hexahistidine peptidyl sequence was generated by standard solid phase peptide synthesis and modified with the succinimidyl ester of iodoacetamide to yield a thiol-reactive iodoacetyl polyhistidine linker.The reactive peptide was conjugated to dye-labeled thiolated DNA which was utilized as a model target biomolecule.Agarose gel electrophoresis and fluorescence resonance energy transfer analysis confirmed that the linker allowed the DNA to self-assemble with quantum dots via metal-affinity driven coordination.In contrast to previous peptidyl linkers that were based on disulfide exchange and were thus labile to reduction,the reactive haloacetyl chemistry demonstrated here results in a more stable thioether bond linking the DNA to the peptide which can withstand strongly reducing environments such as the intracellular cytoplasm.As thiol groups occur naturally in proteins,can be engineered into cloned proteins,inserted into nascent peptides or added to DNA during synthesis,the chemistry demonstrated here can provide a simple method for self-assembling a variety of stable quantum dot bioconjugates.展开更多
文摘As the number of patients receiving total joint replacements continues to rise,considerable attention has been directed towards the early detection and prevention of postoperative complications.While D-dimer has long been studied as a diagnostic tool in venous thromboembolism(VTE),this assay has recently received considerable attention in the diagnosis of periprosthetic joint infection(PJI).D-dimer values are substantially elevated in the acute postoperative period after total joint arthroplasty,with levels often exceeding the standard institutional cutoff for VTE(500µg/L).The utility of D-dimer in detecting VTE after total joint replacement is currently limited,and more research to assess its value in the setting of contemporary prophylaxis protocols is warranted.Recent literature supports D-dimer as a good to excellent biomarker for the diagnosis of chronic PJI,especially when using serum sample technique.Providers should exercise caution when interpreting D-dimer levels in patients with inflammatory and hypercoagulability disorders,as the diagnostic value is decreased.The updated 2018 Musculoskeletal Infection Society criteria,which includes D-dimer levels>860µg/L as a minor criterion,may be the most accurate for diagnosing chronic PJI to date.Larger prospective trials with transparent lab testing protocols are needed to establish best assay practices and optimal cutoff values for D-dimer in the diagnosis of PJI.This review summarizes the most current literature on the value of D-dimer in total joint arthroplasty and elucidates areas for future progress.
基金The National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), DK069939 the Technology Transfer Grant (TTG) by UC Davis Medical Center to Wu J
文摘AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice. METHODS: Mice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX) inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion. RESULTS: A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-α levels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure. CONCLUSION: Allopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generationof superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30670922)INTERNATION Scienc and Techniquie COOPRATION PROGRAM OF CHINA (ISCP) (to Qinghua ZHOU)(No.2006DFB32330)
文摘Background and Objective Lung cancer has the fastest increasing rate of morbidity and mortality all over the world and appears to be one of the most dangerous malignant tumors
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU) (No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU) (No. 30670922)INTERNATION Scienc and Techniquie COOPRATION PROGRAM OF CHINA (ISCP) (to Qinghua ZHOU)(No.2006DFB32330)
文摘Background and objective Lung cancer has not only become the most frequent malignant cancer which is increasing fastest among all the tumors, but also become the rst killer
文摘Abdominal pain with elevated transaminases from inferior vena cava(IVC) obstruction is a relatively common reason for referral and further workup by a hepatologist. The differential for the cause of IVC obstruction is extensive, and the most common etiologies include clotting disorders or recent trauma. In some situations the common etiologies have been ruled out, and the underlying process for the patient's symptoms is still not explained. We present one unique case of abdominal pain and hepatomegaly secondary to IVC constriction from extrinsic compression of the diaphragm. Based on this patient's presentation, we urge that physicians be cognizant of the IVC diameter and consider extrinsic compression as a contributor to the patient's symptoms. If IVC compression from the diaphragm is confirmed, early referral to vascular surgery is strongly advised for further surgical intervention.
文摘Near zero stroke rates can be achieved in carotid endarterectomy (CEA) surgery with selective shunting and electrophysiological neuromonitoring.though false negative rates as high as 40% have been reported.We sought to determine if improved training for interpretation of the monitoring signals can advance the efficacy of selective shunting with electrophysiological monitoring across multiple centers,and determine if other factors could contribute to the differences in reports.Processed and raw beta band (12.5-30 Hz) electroencephalogram (EEG) and median and tibial nerve somatosensory evoked potentials (SSEP) were monitored in 668 CEA cases at six surgical centers.A decrease in amplitude of 50% or more in any EEG or SSEP channel was the criteria for shunting or initiating a neuroprotective protocol.A reduction of 50% or greater in the beta band of the EEG or amplitude of the SSEP was observed in 150 cases.No patient showed signs of a cerebral infarct after surgery.Selective shunting based on EEG and SSEP monitoring can reduce CEA intraoperative stroke rate to a near zero level if trained personnel adopted standardized protocols.We also found that the rapid administration of a protective stroke protocol by attending anesthesiologists was an important aspect of this success rate.
文摘Purpose: To investigate the efficacy of a new algorithm to increase the volume of tissue ablation via gradual ramp-up of power using an internally cooled electrode for ablating hepatomas 3 cm or less. Materials and Methods: 44 patients with 62 hepatomas were treated from March 4, 2004 to May 24, 2009. Ablation with a gradual ramp-up of power was performed using a single needle with an internally cooled electrode. Evaluation for tumor response was performed with 4-phase CT at 24 hours and 3 months. All immediate and follow-up complications were recorded. Results: Complete tumor ablation was achieved in 86%. The ablation volumes were 16 cm3 +/- 12 cm3 for tumors 3 +/- 12 cm3 for tumors 2 - 3 cm. Out of 68 total ablation sessions, there were 2 major complications (pleural effusions) requiring intervention (thoracentesis). Conclusion: Compared with existing techniques using a constant full-power setting, ablation of small hepatomas using an algorithm of gradual ramp-up of power provides comparable rate of complete tumor ablation, adequate ablation volumes, and a low rate of complications that require treatment.
文摘While advanced technology,increased medical knowledge and improved surgical technique has improved patient outcomes in total joint arthroplasty,prosthetic joint infection still remains one of the leading causes of increased healthcare costs,medical resources and societal burdens in orthopaedic care.Two stage arthroplasty revision remains the gold standard for treatment of prosthetic joint infection.Proponents of single stage revision arthroplasty for infection argue that it results in lower healthcare costs while improving patient reported functional outcomes and with equivalent success rates.Here we review the history of single stage revision arthroplasty,discuss the key principles,highlight the indications and contraindications,and review the reported outcomes with a focus on future developments of single stage revision arthroplasty for hip and knee periprosthetic joint infections.
文摘Background: We hypothesized: 1) resected pulmonary typical carcinoid (TC) will show a favorable clinical pattern compared to other bronchopulmonary neuroendocrine tumors (BPNETs);and 2) Atypical carcinoid (AC) and large-cell neuroendocrine carcinoma (LCNEC) patients will have similar outcomes. Methods: The Surveillance Epidemiology and End Result database was queried to compare demographics and tumor specific variables in patients undergoing resection for TC, AC, LCNEC and small cell lung cancer (SCLC) from 2001 to 2006. Results: Similar to LCNEC, AC patients had greater incidence of histologic positive lymph nodes compared to TC (P < 0.001). Survival analysis showed a mean survival of 40.0 ± 1.9 months for SCLC, 46.2 ± 2.2 months for LCNEC, 58.3 ± 2.3 months for AC, and 70.2 ± 0.2 months for TC tumors. TC patients demonstrated favorable survival, and SCLC patients poorer survival, compared to AC and LNEC patients (P < 0.01). Conclusion: AC tumors are a BPNET histology that exhibits clinical behavior distinct from TC. AC tumors should be staged, and treated with stage appropriate therapeutic strategies similar to other non-small cell lung cancers.
基金Supported by NIH grant(DK069939)the Liver Scholar Award by the American Liver Foundation to J.W.
文摘Hepatic fibrosis is a wound healing response, involving pathways of inflammation and fibrogenesis. In response to various insults, such as alcohol, ischemia, viral agents, and medications or hepatotoxins, hepatocyte damage will cause the release of cytokines and other soluble factors by Kupffer cells and other cell types in the liver. These factors lead to activation of hepatic stellate cells, which synthesize large amounts of extracellular matrix components. With chronic injury and fibrosis, liver architecture and metabolism are disrupted, eventually manifesting as cirrhosis and its complications. In addition to eliminating etiology, such as antiviral therapy and pharmacological intervention, it is encouraging that novel strategies are being developed to directly address hepatic injury and fibrosis at the subcellular and molecular levels. With improvement in understanding these mechanisms and pathways, key steps in injury, signaling, activation, and gene expression are being targeted by molecular modalities and other molecular or gene therapy approaches. This article intends to provide an update in terms of the current status of molecular therapy for hepatic injury and fibrosis and how far we are from clinical utilization of these new therapeutic modalities.
文摘AIM:To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease(WD)patients.METHODS:We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent multiple follow-up liver biopsies.Demographic,clinical and laboratory data were gathered and all patients underwent an initial biopsy and at least one repeat biopsy.RESULTS:Time to repeat biopsy ranged from 2 to 12 years.Six patients(non-progressors)showed stable hepatic histology or improvement.In one case,we observed improvement of fibrosis from stage 2 to 0.Six patients(progressors)had worsening of fibrosis.There was no significant correlation between the histological findings and serum aminotransferases or copper me-tabolism parameters.The hepatic copper concentration reached normal levels in only two patients:one from the non-progressors and one from the progressors group.The estimated rate of progression of hepatic fibrosis in the entire group was 0 units per year in the time frame between the first and the second liver biopsy(4 years),and 0.25 between the second and the third(3 years).In the progressors group,the rate of progression of liver fibrosis was estimated at 0.11 fibrosis units per year between the first and second biopsy and,0.6 fibrosis units between the second and third biopsy.CONCLUSION:The inability of clinical tools to detect fibrosis progression in WD suggests that a liver biopsy with hepatic copper quantification every 3 years should be considered.
文摘Laparoscopic liver resection (LLR) for the treatment of benign and malignant liver lesions is often performed at specialized centers. Technological advances, such as laparoscopic ultrasonography and electrosurgical tools, have afforded surgeons simultaneous improvements in surgical technique. The utilization of minimally invasive techniques for liver resection has been reported to reduce operative time, decrease blood loss, and shorten length of hospital stay with equivalent postoperative mortality and morbidity rates compared to open liver resection (OLR). Non-anatomic liver resection and left lateral sectionectomy are now routinely performed laparoscopically at many institutions. Furthermore, major hepatic resections are performed by pure laparoscopy, hand-assisted technique, and the hybrid method. In addition, robotic surgery and single port surgery are revealing early promising results. The consensus recommendation for the treatment of benign liver disease and malignant lesions remains unchanged when considering a laparoscopic approach, except when comorbidities and anatomic limitations of the liver lesion preclude this technique. Disease free and survival rates after LLR for hepatocellular carcinoma and metastatic colon cancer correspond to OLR. Patient selection is a significant factor for these favorable outcomes. The limitations include LLR of superior and posterior liver lesions; however, adjustments in technique may now consider a laparoscopic approach as a viable option. As growing data continue to reveal the feasibility and efficacy of laparoscopic liver surgery, this skill is increasingly being adopted by hepatobiliary surgeons. Although the full scope of laparoscopic liver surgery remains infrequently used by many general surgeons, this technique will become a standard in the treatment of liver diseases as studies continue to show favorable outcomes.
文摘Endoscopic ultrasound(EUS)is a minimally invasive diagnostic and therapeutic modality with a number of established as well as evolving uses in patients with chronic liver disease.Compared to other diagnostic tools such as cross-sectional imaging or conventional endoscopy,EUS has been shown to increase diagnostic sensitivity and therapeutic success for many clinical scenarios and applications with a low rate of adverse events.In this review,we discuss and focus on the current and growing role of EUS in the evaluation and/or treatment of hepatobiliary masses,hepatic parenchymal disease,portal hypertension,esophageal and other varices,and indeterminate biliary strictures.
文摘Objective: To evaluate the effectiveness of Shenqi Fuzheng Injection (参芪扶正注射液, SFI) combined with chemotherapy for advanced gastric cancer. Methods: Randomized controlled trials (RCTs) from 10 databases were searched for this meta-analysis till December 31, 2012 without language restriction. Grey literature and potential unpublished literature was also searched. The key search terms were "chemotherapy", "Shenqi Fuzheng Injection" and "advanced gastric cancer". Criteria were built to select these clinical trials, in which SFI combined with chemotherapy was compared with chemotherapy alone for advanced gastric cancer. The methodological quality of each RCT was assessed using the Cochrane risk of bias tool. RevMan 5.1 software was applied for data analyses. Results: Thirteen RCTs involving 860 patients met the selection criteria (all articles were from Chinese databases). The meta-analysis showed positive results for the use of SFI combined with chemotherapy according to quality of life in terms of the scores when compared with chemotherapy alone. Positive results were also obtained for the combination treatment, in terms of complete remission and partial remission efficacy rate, body weight and decreased adverse events including nausea and vomiting at grade 3-4, oral mucositis at grade 1-2, leucopenia at grade 3-4, and myelo-suppression at grade 1-2. Conclusions: This systematic review found encouraging albeit limited evidence for SFI combined with chemotherapy. However, to obtain stronger evidence without the drawbacks of trial design and the quality of studies, we recommend comparative effectiveness researches to test the effectiveness of combination treatment.
基金The authors acknowledge Stephen Lee and Ilya Elashvilli of the CB Directorate/Physical S&T Division(DTRA),ONR,NRL,and the NRLNSI for financial support.
文摘We demonstrate improved peptide linkers which allow both conjugation to biomolecules such as DNA and self-assembly with luminescent semiconductor quantum dots.A hexahistidine peptidyl sequence was generated by standard solid phase peptide synthesis and modified with the succinimidyl ester of iodoacetamide to yield a thiol-reactive iodoacetyl polyhistidine linker.The reactive peptide was conjugated to dye-labeled thiolated DNA which was utilized as a model target biomolecule.Agarose gel electrophoresis and fluorescence resonance energy transfer analysis confirmed that the linker allowed the DNA to self-assemble with quantum dots via metal-affinity driven coordination.In contrast to previous peptidyl linkers that were based on disulfide exchange and were thus labile to reduction,the reactive haloacetyl chemistry demonstrated here results in a more stable thioether bond linking the DNA to the peptide which can withstand strongly reducing environments such as the intracellular cytoplasm.As thiol groups occur naturally in proteins,can be engineered into cloned proteins,inserted into nascent peptides or added to DNA during synthesis,the chemistry demonstrated here can provide a simple method for self-assembling a variety of stable quantum dot bioconjugates.