Background: Cause-of-death rankings are often used for planning or evaluating health policy measures. In the European Union, some countries produce cause-of-death statistics by a manual coding of death certificates, w...Background: Cause-of-death rankings are often used for planning or evaluating health policy measures. In the European Union, some countries produce cause-of-death statistics by a manual coding of death certificates, while other countries use an automated coding system. The outcome of these two different methods in terms of the selected underlying cause of death for statistics may vary considerably. Therefore, this study explores the effect of coding method on the ranking of countries by major causes of death. Method: Age and sex standardized rates were extracted for 33 European (related) countries from the cause-of-death registry of the European Statistical Office (Eurostat). Wilcoxon’s rank sum test was applied to the ranking of countries by major causes of death. Results: Statistically significant differences due to coding method were identified for dementia, stroke and pneumonia. These differences could be explained by a different selection of dementia or pneumonia as underlying cause of death and by a different certification practice for stroke. Conclusion: Coding method should be taken into account when constructing or interpreting rankings of countries by cause of death.展开更多
Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1(PD-1) and program death-ligand 1(PD-L1) will lead the...Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1(PD-1) and program death-ligand 1(PD-L1) will lead the activated T cell to a state of anergy. PD-L1 is upregulated on a wide range of cancer cells. Anti-PD-1 and anti-PD-L1 monoclonal antibodies(m Abs), called immune checkpoint inhibitors(ICIs), have consequently been designed to restore T cell activity. Accumulating data are in favor of an association between PD-L1 expression in tumors and response to treatment. A PD-L1 expression is present in 30% to 50% of digestive cancers. Multiple anti-PD-1(nivolumab, pembrolizumab) and anti-PD-L1 m Abs(MPDL3280A, Medi4736) are under evaluation in digestive cancers. Preliminary results in metastatic gastric cancer with pembrolizumab are highly promising and phase Ⅱ will start soon. In metastatic colorectal cancer(CRC), a phase Ⅲ trial of MPDL3280 A as maintenance therapy will shortly be initiated. Trials are also ongoing in metastatic CRC with high immune T cell infiltration(i.e., microsatellite instability). Major challenges are ahead in order to determine how, when and for which patients we should use these ICIs. New radiologic criteria to evaluate tumor response to ICIs are awaiting prospective validation. The optimal therapeutic sequence and association with cytotoxic chemotherapy needs to be established. Finally, biomarker identification will be crucial to selection ofpatients likely to benefit from ICIs.展开更多
Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen ...Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by aug- menting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were col- lected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ±0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P〈0.05). And there was no significant difference between DBD group and DBCD group (P〉0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.展开更多
Objective: To evaluate the population attributable risks (PARs) between cigarette smoking and deaths of all causes, all cancers, lung cancer and other chronic diseases in urban Shanghai. Methods: In total, 61,480 ...Objective: To evaluate the population attributable risks (PARs) between cigarette smoking and deaths of all causes, all cancers, lung cancer and other chronic diseases in urban Shanghai. Methods: In total, 61,480 men aged 40-74 years from 2002 to 2006 and 74,941 women aged 40-70 years from 1997 to 2000 were recruited to undergo baseline surveys in urban Shanghai, with response rates of 74.0% and 92.3%, respectively. A Cox proportional hazards regression model was used to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) of deaths associated with cigarette smoking. PARs and 95 % CIs for deaths were estimated from smoking exposure rates and the estimated RRs. Results: Cigarette smoking was responsible for 23.9% (95% CI: 19.4-28.3%) and 2.4% (95% Ch 1.6- 3.2%) of all deaths in men and women, respectively, in our study population. Respiratory disease had the highest PAR in men [37.5% (95% CI: 21.5-51.6%)], followed by cancer [31.3% (95% Ch 24.6-37.7%)] and cardiovascular disease (CVD) [24.1% (95% CI: 16.7-31.2%)]. While the top three PARs were 12.7% (95% CI: 6.1-19.3%), 4.0% (95% CI: 2.4-5.6%), and 1.1% (95% CI: 0.0-2.3%), for respiratory disease, CVD, and cancer, respectively in women. For deaths of lung cancer, the PAR of smoking was 68.4% (95% CI: 58.2- 76.5%) in men. Conclusions: In urban Shanghai, 23.9% and 2.4% of all deaths in men and women could have been prevented if no people had smoked in the area. Effective control programs against cigarette smoking should be strongly advocated to reduce the increasing smoking-related death burden.展开更多
Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroes...Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer.展开更多
Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses...Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.展开更多
BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, t...BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, the role of PD-1/PD-L1 pathway in gastric neuroendocrine carcinomas(G-NECs) remains unknown.AIM To investigate the expression of PD-1/PD-L1 and role of PD-1/PD-L1 pathway in G-NECs, which occur rarely but are highly malignant and clinically defiant.METHODS We investigated the expression of PD-L1 on tumor cells and PD-1^+, CD8^+, and FOXP3^+ T cell infiltration by immunohistochemistry in 43 resected G-NEC tissue specimens. The copy number alterations of PD-L1 were assessed by qRT-PCR.RESULTS Most of the G-NECs tumor cells exhibited a near-uniform expression pattern of PD-L1, while some showed a tumor-stromal interface enhanced pattern. Of the 43G-NECs, 21(48.8%) were classified as a high PD-L1 expression group, and the high expression of PD-L1 was associated with poor overall survival(OS). The high expression of PD-L1 was correlated with abundant PD-1^+ tumor infiltrating lymphocytes(TILs) instead of CD8^+ TILs and FOXP3^+ regulatory T cells(Tregs).Our analysis also suggested that the infiltration of CD8^+ TILs tended to be a favorable factor for OS, although the difference did not reach the statistical significance(P = 0.065). Meanwhile, PD-L1 was significantly overexpressed in cases with copy number gain as compared with those without.CONCLUSION Our data demonstrated for the first time that high expression of PD-L1 in GNECs is associated with a poor prognosis, while the high expression may be due to the copy number variation of PD-L1 gene or stimulation of TILs. These results provide a basis for the immunotherapy targeting PD-1/PD-L1 pathway in GNECs.展开更多
Objectives: The aim of the study was to examine the process of community maternal, neonatal deaths and still births notification within the Bangladesh government health structure using the Maternal and Neonatal Death ...Objectives: The aim of the study was to examine the process of community maternal, neonatal deaths and still births notification within the Bangladesh government health structure using the Maternal and Neonatal Death Review (MNDR) system. The study also explored the feasibility and acceptance of community death notification in the MNDR system. Methods: The study was under-taken in the Thakurgaon district of Bangladesh during 2010. During the study a mix of both qualitative and quantitative information was collected. A review of the documentation process of community death notification was undertaken and focus group discussions (FGDs) with community members, health care providers and managers in a sub-district were conducted, with in-depth interviews (IDIs) with district heath and family planning managers. Quantitative data were collected from community death notifications in the district during January to December 2010. Results: The death notification process was implemented by the government health care system within the Thakurgaon district. Field level health and family planning staff collected maternal and neonatal death information, recorded the death on the notification form and reported back to the Upazila (sub-district of the district) focal point at the Upazila health complex (primary health care centre). Community people were encouraged to share their death information to field level health staff. The health and family planning managers in the district periodically discussed the maternal and neonatal deaths and prepared remedial action plans in high death notified areas. In 2010, 59 maternal deaths, 739 neonatal deaths and 633 still births were reported in Thakurgaon district. District health and family planning departments performed community death notification as part of their routine daily work and integrated these procedures with other field level activities. Conclusion: Community death notification under the MNDR system was found to be achievable and acceptable at the district level using the existing government health system. The simple death notification process used to capture community level maternal, neonatal deaths and still births provides a guide for planning corrective actions for better health outcomes for the community.展开更多
A review of the literature suggests that errors in death certification are common. We reviewed the published literature to clarify what is known and what remains to be learned before evidence-based changes in medical ...A review of the literature suggests that errors in death certification are common. We reviewed the published literature to clarify what is known and what remains to be learned before evidence-based changes in medical education can be recommended. We searched the National Library of Medicine’s PubMed database for articles that addressed death certificate accuracy and identified 159 articles of interest published from 1996 to 2010. Among these 159 articles, we found 83 that were relevant to our goals and objectives. Cause of death certification has been shown to be problematic and several interventions have been shown to improve its accuracy, especially if the intervention is interactive. However these studies have focused on short term gains rather than on long term retention and performance, leaving a significant data gap. We suggest a study design that could address this data gap.展开更多
This paper combines the analytical explanation of Dickinson's death-themed poems with her life experience of religion and death experience to reveal her positive attitude towards life and death.
Objective: To study causes of maternal mortality according to reports of maternal death audits in the University Teaching Hospital Bogodogo (UTH-B) of Ouagadougou, Burkina Faso. Materials and Method: This was a prospe...Objective: To study causes of maternal mortality according to reports of maternal death audits in the University Teaching Hospital Bogodogo (UTH-B) of Ouagadougou, Burkina Faso. Materials and Method: This was a prospective study that took place over a year from 1 January to 31 December 2017.? It concerned maternal deaths that occurred during this period in the obstetrics and gynecology department of the University Teaching Hospital Bogodogo (UTH-B). All maternal deaths were systematically audited by the audit committee;interviews with providers and families were sometimes conducted. The record books of all patients were analyzed by the audit committee;if necessary, interviews were conducted with care providers and families. The main information collected were recorded on individual files, entered and analyzed using the software Epi-info 7. Result: During the study period, we recorded 32 maternal deaths i.e., 587 per 100,000 live births. Deceased women under age 20 were the most numerous, followed by women aged 20 to 24. The death occurred in most cases in the puerperium in 69.80% of cases. Complications of pregnancy were the most incriminated causes in maternal deaths. Bleeding was the leading cause, accounting for 34.3%. They are followed by hypertensive disorders of pregnancy (21.8%) and infections (18.8%). In the contributing factors, resource factors were incriminated in 56.2% of cases, social factors in 43.7% of cases and medical factors in 25.4% of cases. Death was non-preventable in 76.2% of cases compared to 23.8% of preventable deaths. Conclusion: Maternal mortality is a major public health problem at the maternity hospital of the university hospital Yalgado Ouedraogo. Hemorrhage is the first cause of death. Hypertensive diseases are more and more worrying. Solutions must be found to improve the practice of audits in the obstetrics and gynecology department of UTH-B.展开更多
In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is...In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is considered to be an effective treatment for advanced HCC.Immune checkpoint inhibitors targeting programmed cell death 1(PD-1)/programmed cell death ligand 1(PDL1)are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced HCC.However,treating advanced HCC is still a great challenge,and the need for new treatments remains urgent.This review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC.展开更多
Objective: To investigate the epidemiological characteristics and relative factor about hospital death in patients with road traffic trauma. Methods: The age, sex, road-use category, sites of injury, injury severity s...Objective: To investigate the epidemiological characteristics and relative factor about hospital death in patients with road traffic trauma. Methods: The age, sex, road-use category, sites of injury, injury severity scale of 159 hospital death cases in 2436 cases with road traffic trauma were observed, and the relation between the causes of death and time elapsed after injury was also studied with likelihood ratio Chi-square test.展开更多
AIM: To evaluate the accuracy of a tool developed to predict timing of death following withdrawal of life support in children. METHODS: Pertinent variables for all pediatric deaths(age ≤ 21 years) from 1/2009 to 6/20...AIM: To evaluate the accuracy of a tool developed to predict timing of death following withdrawal of life support in children. METHODS: Pertinent variables for all pediatric deaths(age ≤ 21 years) from 1/2009 to 6/2014 in our pediatric intensive care unit(PICU) were extracted through a detailed review of the medical records. As originally described, a recently developed tool that predicts timing of death in children following withdrawal of life support(dallas predictor tool [DPT]) was used to calculate individual scores for each patient. Individual scores were calculated for prediction of death within 30 min(DPT30) and within 60 min(DPT60). For various resulting DPT30 and DPT60 scores, sensitivity, specificity and area under the receiver operating characteristic curve were calculated.RESULTS: There were 8829 PICU admissions resulting in 132(1.5%) deaths. Death followed withdrawal of life support in 70 patients(53%). After excluding subjects with insufficient data to calculate DPT scores, 62 subjects were analyzed. Average age of patients was 5.3 years(SD: 6.9), median time to death after withdrawal oflife support was 25 min(range; 7 min to 16 h 54 min). Respiratory failure, shock and sepsis were the most common diagnoses. Thirty-seven patients(59.6%) died within 30 min of withdrawal of life support and 52(83.8%) died within 60 min. DPT30 scores ranged from-17 to 16. A DPT30 score ≥-3 was most predictive of death within that time period, with sensitivity = 0.76, specificity = 0.52, AUC = 0.69 and an overall classification accuracy = 66.1%. DPT60 scores ranged from-21 to 28. A DPT60 score ≥-9 was most predictive of death within that time period, with sensitivity = 0.75, specificity = 0.80, AUC = 0.85 and an overall classification accuracy = 75.8%.CONCLUSION: In this external cohort, the DPT is clinically relevant in predicting time from withdrawal of life support to death. In our patients, the DPT is more useful in predicting death within 60 min of withdrawal of life support than within 30 min. Furthermore, our analysis suggests optimal cut-off scores. Additional calibration and modifications of this important tool could help guide the intensive care team and families considering DCD.展开更多
The purpose of this study was to explore and describe the experiences of community stakeholders on reporting community maternal deaths to relevant authorities in Mangochi District of Malawi. The study employed qualita...The purpose of this study was to explore and describe the experiences of community stakeholders on reporting community maternal deaths to relevant authorities in Mangochi District of Malawi. The study employed qualitative hermeneutic phenomenology approach to data collection, analysis and interpretation. It was conducted in three health zones of Mangochi district which are Monkey-bay, Mangochi boma and Namwera zones. Purposive sampling was used to select major community stakeholders on issues of safe motherhood and these were;Village heads, Health Surveillance Assistants (HSAs), safe motherhood volunteers and members of village health committees (VHCs). A total of eighteen in-depth interviews and three focus group discussions were conducted. Descriptive statistics were computed for the demographic variables and the qualitative data were analysed using modified Colaizzi (1978) method based on Heideggerian and Gademerian philosophy. Findings showed that community maternal deaths were not always reported because there were no records in the district. Most participants lacked knowledge on the process and their role in reporting community maternal deaths despite knowing the importance of reporting such deaths. However, findings indicated a positive perception of participants towards reporting community maternal deaths to authorities. The study recommends that health education be offered to community members and Health Surveillance Assistants regarding reporting maternal deaths to improve the situation.展开更多
文摘Background: Cause-of-death rankings are often used for planning or evaluating health policy measures. In the European Union, some countries produce cause-of-death statistics by a manual coding of death certificates, while other countries use an automated coding system. The outcome of these two different methods in terms of the selected underlying cause of death for statistics may vary considerably. Therefore, this study explores the effect of coding method on the ranking of countries by major causes of death. Method: Age and sex standardized rates were extracted for 33 European (related) countries from the cause-of-death registry of the European Statistical Office (Eurostat). Wilcoxon’s rank sum test was applied to the ranking of countries by major causes of death. Results: Statistically significant differences due to coding method were identified for dementia, stroke and pneumonia. These differences could be explained by a different selection of dementia or pneumonia as underlying cause of death and by a different certification practice for stroke. Conclusion: Coding method should be taken into account when constructing or interpreting rankings of countries by cause of death.
文摘Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1(PD-1) and program death-ligand 1(PD-L1) will lead the activated T cell to a state of anergy. PD-L1 is upregulated on a wide range of cancer cells. Anti-PD-1 and anti-PD-L1 monoclonal antibodies(m Abs), called immune checkpoint inhibitors(ICIs), have consequently been designed to restore T cell activity. Accumulating data are in favor of an association between PD-L1 expression in tumors and response to treatment. A PD-L1 expression is present in 30% to 50% of digestive cancers. Multiple anti-PD-1(nivolumab, pembrolizumab) and anti-PD-L1 m Abs(MPDL3280A, Medi4736) are under evaluation in digestive cancers. Preliminary results in metastatic gastric cancer with pembrolizumab are highly promising and phase Ⅱ will start soon. In metastatic colorectal cancer(CRC), a phase Ⅲ trial of MPDL3280 A as maintenance therapy will shortly be initiated. Trials are also ongoing in metastatic CRC with high immune T cell infiltration(i.e., microsatellite instability). Major challenges are ahead in order to determine how, when and for which patients we should use these ICIs. New radiologic criteria to evaluate tumor response to ICIs are awaiting prospective validation. The optimal therapeutic sequence and association with cytotoxic chemotherapy needs to be established. Finally, biomarker identification will be crucial to selection ofpatients likely to benefit from ICIs.
基金supported by grants from the National High Technology Research and Development Program of China(863 Program)(No.2012AA021008)the Special Fund for Science Research by Ministry of Health(No.201302009)+2 种基金the Key Clinical Specialty Construction Project of National Health and Family Planning Commission of the People’s Republic of Chinathe Science and Technology Planning Key Clinical Project of Guangdong Province(No.2011A030400005)the Key Laboratory Construction Project of Guangdong Province
文摘Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by aug- menting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were col- lected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ±0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P〈0.05). And there was no significant difference between DBD group and DBCD group (P〉0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.
基金supported by the funds of Key Discipline and Specialty Foundation of Shanghai Municipal Commission of Health and Family Planningthe National Key Basic Research Program "973 project" (2015CB554000)grants from US National Institutes of Health (R37 CA070867, R01 CA82729, UM1CA173640, and UM1 CA182910)
文摘Objective: To evaluate the population attributable risks (PARs) between cigarette smoking and deaths of all causes, all cancers, lung cancer and other chronic diseases in urban Shanghai. Methods: In total, 61,480 men aged 40-74 years from 2002 to 2006 and 74,941 women aged 40-70 years from 1997 to 2000 were recruited to undergo baseline surveys in urban Shanghai, with response rates of 74.0% and 92.3%, respectively. A Cox proportional hazards regression model was used to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) of deaths associated with cigarette smoking. PARs and 95 % CIs for deaths were estimated from smoking exposure rates and the estimated RRs. Results: Cigarette smoking was responsible for 23.9% (95% CI: 19.4-28.3%) and 2.4% (95% Ch 1.6- 3.2%) of all deaths in men and women, respectively, in our study population. Respiratory disease had the highest PAR in men [37.5% (95% CI: 21.5-51.6%)], followed by cancer [31.3% (95% Ch 24.6-37.7%)] and cardiovascular disease (CVD) [24.1% (95% CI: 16.7-31.2%)]. While the top three PARs were 12.7% (95% CI: 6.1-19.3%), 4.0% (95% CI: 2.4-5.6%), and 1.1% (95% CI: 0.0-2.3%), for respiratory disease, CVD, and cancer, respectively in women. For deaths of lung cancer, the PAR of smoking was 68.4% (95% CI: 58.2- 76.5%) in men. Conclusions: In urban Shanghai, 23.9% and 2.4% of all deaths in men and women could have been prevented if no people had smoked in the area. Effective control programs against cigarette smoking should be strongly advocated to reduce the increasing smoking-related death burden.
文摘Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer.
文摘Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.
基金Supported by Municipal Commission of Health and Family Planning of Shanghai,China(No.20174Y0243 to Liu DJ,No.20154Y0163 to Chen XJ)Cultivating Funds of Renji Hospital,School of Medicine,Shanghai Jiao Tong University,China(No.PYXJS 16-002 to Liu W)
文摘BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, the role of PD-1/PD-L1 pathway in gastric neuroendocrine carcinomas(G-NECs) remains unknown.AIM To investigate the expression of PD-1/PD-L1 and role of PD-1/PD-L1 pathway in G-NECs, which occur rarely but are highly malignant and clinically defiant.METHODS We investigated the expression of PD-L1 on tumor cells and PD-1^+, CD8^+, and FOXP3^+ T cell infiltration by immunohistochemistry in 43 resected G-NEC tissue specimens. The copy number alterations of PD-L1 were assessed by qRT-PCR.RESULTS Most of the G-NECs tumor cells exhibited a near-uniform expression pattern of PD-L1, while some showed a tumor-stromal interface enhanced pattern. Of the 43G-NECs, 21(48.8%) were classified as a high PD-L1 expression group, and the high expression of PD-L1 was associated with poor overall survival(OS). The high expression of PD-L1 was correlated with abundant PD-1^+ tumor infiltrating lymphocytes(TILs) instead of CD8^+ TILs and FOXP3^+ regulatory T cells(Tregs).Our analysis also suggested that the infiltration of CD8^+ TILs tended to be a favorable factor for OS, although the difference did not reach the statistical significance(P = 0.065). Meanwhile, PD-L1 was significantly overexpressed in cases with copy number gain as compared with those without.CONCLUSION Our data demonstrated for the first time that high expression of PD-L1 in GNECs is associated with a poor prognosis, while the high expression may be due to the copy number variation of PD-L1 gene or stimulation of TILs. These results provide a basis for the immunotherapy targeting PD-1/PD-L1 pathway in GNECs.
文摘Objectives: The aim of the study was to examine the process of community maternal, neonatal deaths and still births notification within the Bangladesh government health structure using the Maternal and Neonatal Death Review (MNDR) system. The study also explored the feasibility and acceptance of community death notification in the MNDR system. Methods: The study was under-taken in the Thakurgaon district of Bangladesh during 2010. During the study a mix of both qualitative and quantitative information was collected. A review of the documentation process of community death notification was undertaken and focus group discussions (FGDs) with community members, health care providers and managers in a sub-district were conducted, with in-depth interviews (IDIs) with district heath and family planning managers. Quantitative data were collected from community death notifications in the district during January to December 2010. Results: The death notification process was implemented by the government health care system within the Thakurgaon district. Field level health and family planning staff collected maternal and neonatal death information, recorded the death on the notification form and reported back to the Upazila (sub-district of the district) focal point at the Upazila health complex (primary health care centre). Community people were encouraged to share their death information to field level health staff. The health and family planning managers in the district periodically discussed the maternal and neonatal deaths and prepared remedial action plans in high death notified areas. In 2010, 59 maternal deaths, 739 neonatal deaths and 633 still births were reported in Thakurgaon district. District health and family planning departments performed community death notification as part of their routine daily work and integrated these procedures with other field level activities. Conclusion: Community death notification under the MNDR system was found to be achievable and acceptable at the district level using the existing government health system. The simple death notification process used to capture community level maternal, neonatal deaths and still births provides a guide for planning corrective actions for better health outcomes for the community.
文摘A review of the literature suggests that errors in death certification are common. We reviewed the published literature to clarify what is known and what remains to be learned before evidence-based changes in medical education can be recommended. We searched the National Library of Medicine’s PubMed database for articles that addressed death certificate accuracy and identified 159 articles of interest published from 1996 to 2010. Among these 159 articles, we found 83 that were relevant to our goals and objectives. Cause of death certification has been shown to be problematic and several interventions have been shown to improve its accuracy, especially if the intervention is interactive. However these studies have focused on short term gains rather than on long term retention and performance, leaving a significant data gap. We suggest a study design that could address this data gap.
文摘This paper combines the analytical explanation of Dickinson's death-themed poems with her life experience of religion and death experience to reveal her positive attitude towards life and death.
文摘Objective: To study causes of maternal mortality according to reports of maternal death audits in the University Teaching Hospital Bogodogo (UTH-B) of Ouagadougou, Burkina Faso. Materials and Method: This was a prospective study that took place over a year from 1 January to 31 December 2017.? It concerned maternal deaths that occurred during this period in the obstetrics and gynecology department of the University Teaching Hospital Bogodogo (UTH-B). All maternal deaths were systematically audited by the audit committee;interviews with providers and families were sometimes conducted. The record books of all patients were analyzed by the audit committee;if necessary, interviews were conducted with care providers and families. The main information collected were recorded on individual files, entered and analyzed using the software Epi-info 7. Result: During the study period, we recorded 32 maternal deaths i.e., 587 per 100,000 live births. Deceased women under age 20 were the most numerous, followed by women aged 20 to 24. The death occurred in most cases in the puerperium in 69.80% of cases. Complications of pregnancy were the most incriminated causes in maternal deaths. Bleeding was the leading cause, accounting for 34.3%. They are followed by hypertensive disorders of pregnancy (21.8%) and infections (18.8%). In the contributing factors, resource factors were incriminated in 56.2% of cases, social factors in 43.7% of cases and medical factors in 25.4% of cases. Death was non-preventable in 76.2% of cases compared to 23.8% of preventable deaths. Conclusion: Maternal mortality is a major public health problem at the maternity hospital of the university hospital Yalgado Ouedraogo. Hemorrhage is the first cause of death. Hypertensive diseases are more and more worrying. Solutions must be found to improve the practice of audits in the obstetrics and gynecology department of UTH-B.
基金Supported by CAMS Innovation Fund for Medical Science(CIFMS),No.CAMS-2016-I2M-3-025Beijing Hope Run Special Fund of Cancer Foundation of China,No.LC2020L05.
文摘In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is considered to be an effective treatment for advanced HCC.Immune checkpoint inhibitors targeting programmed cell death 1(PD-1)/programmed cell death ligand 1(PDL1)are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced HCC.However,treating advanced HCC is still a great challenge,and the need for new treatments remains urgent.This review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC.
文摘Objective: To investigate the epidemiological characteristics and relative factor about hospital death in patients with road traffic trauma. Methods: The age, sex, road-use category, sites of injury, injury severity scale of 159 hospital death cases in 2436 cases with road traffic trauma were observed, and the relation between the causes of death and time elapsed after injury was also studied with likelihood ratio Chi-square test.
基金Supported by Health Resources and Services Administration,NO.234-2005-37011C
文摘AIM: To evaluate the accuracy of a tool developed to predict timing of death following withdrawal of life support in children. METHODS: Pertinent variables for all pediatric deaths(age ≤ 21 years) from 1/2009 to 6/2014 in our pediatric intensive care unit(PICU) were extracted through a detailed review of the medical records. As originally described, a recently developed tool that predicts timing of death in children following withdrawal of life support(dallas predictor tool [DPT]) was used to calculate individual scores for each patient. Individual scores were calculated for prediction of death within 30 min(DPT30) and within 60 min(DPT60). For various resulting DPT30 and DPT60 scores, sensitivity, specificity and area under the receiver operating characteristic curve were calculated.RESULTS: There were 8829 PICU admissions resulting in 132(1.5%) deaths. Death followed withdrawal of life support in 70 patients(53%). After excluding subjects with insufficient data to calculate DPT scores, 62 subjects were analyzed. Average age of patients was 5.3 years(SD: 6.9), median time to death after withdrawal oflife support was 25 min(range; 7 min to 16 h 54 min). Respiratory failure, shock and sepsis were the most common diagnoses. Thirty-seven patients(59.6%) died within 30 min of withdrawal of life support and 52(83.8%) died within 60 min. DPT30 scores ranged from-17 to 16. A DPT30 score ≥-3 was most predictive of death within that time period, with sensitivity = 0.76, specificity = 0.52, AUC = 0.69 and an overall classification accuracy = 66.1%. DPT60 scores ranged from-21 to 28. A DPT60 score ≥-9 was most predictive of death within that time period, with sensitivity = 0.75, specificity = 0.80, AUC = 0.85 and an overall classification accuracy = 75.8%.CONCLUSION: In this external cohort, the DPT is clinically relevant in predicting time from withdrawal of life support to death. In our patients, the DPT is more useful in predicting death within 60 min of withdrawal of life support than within 30 min. Furthermore, our analysis suggests optimal cut-off scores. Additional calibration and modifications of this important tool could help guide the intensive care team and families considering DCD.
文摘The purpose of this study was to explore and describe the experiences of community stakeholders on reporting community maternal deaths to relevant authorities in Mangochi District of Malawi. The study employed qualitative hermeneutic phenomenology approach to data collection, analysis and interpretation. It was conducted in three health zones of Mangochi district which are Monkey-bay, Mangochi boma and Namwera zones. Purposive sampling was used to select major community stakeholders on issues of safe motherhood and these were;Village heads, Health Surveillance Assistants (HSAs), safe motherhood volunteers and members of village health committees (VHCs). A total of eighteen in-depth interviews and three focus group discussions were conducted. Descriptive statistics were computed for the demographic variables and the qualitative data were analysed using modified Colaizzi (1978) method based on Heideggerian and Gademerian philosophy. Findings showed that community maternal deaths were not always reported because there were no records in the district. Most participants lacked knowledge on the process and their role in reporting community maternal deaths despite knowing the importance of reporting such deaths. However, findings indicated a positive perception of participants towards reporting community maternal deaths to authorities. The study recommends that health education be offered to community members and Health Surveillance Assistants regarding reporting maternal deaths to improve the situation.