Factors involved in health-related transitions after curative resection for pancreatic cancer. 10-Years experience: A multi state model

Background: Pancreatic cancer is one of the least common tumours, nevertheless it is one of the most lethal. This lethality is mainly due to the fact that the vast majority of patients are diagnosed in an advanced stage. The purpose of this study was to investigate how different covariates affect the transition to death or discharge with and without complications after pancreatic resection. Methods: We analyse the impact of different factors on transitions after pancreatic resection based on a multi state model. Results: Transitions of interest include the transition to death/discharge with/without complications after pancreatic resection. We consider presence of comorbidities, higher age (>60), gender-male, lower hospital volume (<10 cases per year), type of surgery, localization of tumour and transfusion received as covariates with a potentially negative effect on the transition intensities to death with or without complications. Conclusions: The multi-state model allows for a very detailed analysis of the impact of covariates on each transition, since effects of covariates may change depending on the current state of the patient, thus helping surgeons and patients throughout the surgical process and counselling patients if needed.     

Valor pronóstico del diagnóstico principal en ancianos ingresados en una unidad geriátrica de agudos al alta y al año

ObjectiveTo analyse the relationship between the primary diagnosis on admission to an Acute Geriatric Unit (AGU) and the risk of hospital mortality and one year after dischargeMaterial and methodsA longitudinal study was conducted on patients admitted to the Central Hospital AGU Red Cross in Madrid in 2009. The admission diagnosis was grouped by Diagnosis Related Groups (DRGs). The date of death was collected from the medical charts and the National Death Index Ministry of Health report. The main outcome of study was the association between diagnoses on admission and functional impairment at discharge (measured as a loss of 10 or more points between the Barthel Index at discharge and that on admission), mortality during hospitalization, at 3 months and one year after discharge. The multivariate analysis was adjusted for age, sex, comorbidity, functional and cognitive status, and serum albumin.ResultsThe study included1147 patients, with a mean age of 86.7 years (SD ± 6.7), and 66% were women. During admission, 10.1% of patients died and 36.6% had functional impairment at discharge. After discharge, 25.5% died at 3 months, and 42.2% at one year. The distribution of the primary diagnoses at admission (between parentheses hospital mortality and at year) were heart failure, 21.4% (8.1% and 37.4%), pneumonia,13.3% (12.3% and 46.4%), and aspiration pneumonia, 4.7% (27.5%, y 71%), respiratory diseases,13.3% (6.6% and 38.2%), urinary infection,10.2% (5.1% and 42.7%), and stroke (excluding AIT), 9.9% (13.3% and 46.9%). In the multivariate analysis, only admissions due to aspiration pneumonia were independently associated with increased risk of hospital mortality (odds ratio, 2.23; 95% CI = 1.13 to 44.42), and stroke with increased risk of functional impairment at discharge (odds ratio, 6.01; 95% CI = 3.42-10.57). No diagnosis was independently associated with increased risk of death at 3 months and at yearConclusionsAdmission from aspiration pneumonia carries an increased risk of death in elderly patients hospitalised for acute medical conditions. After discharge, the risk of death must be attributed to factors other than the admission diagnosis     

Fatal opioid overdoses during and shortly after hospital admissions in England: A case-crossover study

BackgroundHospital patients who use illicit opioids such as heroin may use drugs during an admission or leave the hospital in order to use drugs. There have been reports of patients found dead from drug poisoning on the hospital premises or shortly after leaving the hospital. This study examines whether hospital admission and discharge are associated with increased risk of opioid-related death.Methods and findingsWe conducted a case-crossover study of opioid-related deaths in England. Our study included 13,609 deaths between January 1, 2010 and December 31, 2019 among individuals aged 18 to 64. For each death, we sampled 5 control days from the period 730 to 28 days before death. We used data from the national Hospital Episode Statistics database to determine the time proximity of deaths and control days to hospital admissions. We estimated the association between hospital admission and opioid-related death using conditional logistic regression, with a reference category of time neither admitted to the hospital nor within 14 days of discharge. A total of 236/13,609 deaths (1.7%) occurred following drug use while admitted to the hospital. The risk during hospital admissions was similar or lower than periods neither admitted to the hospital nor recently discharged, with odds ratios 1.03 (95% CI 0.87 to 1.21; p = 0.75) for the first 14 days of an admission and 0.41 (95% CI 0.30 to 0.56; p < 0.001) for days 15 onwards. 1,088/13,609 deaths (8.0%) occurred in the 14 days after discharge. The risk of opioid-related death increased in this period, with odds ratios of 4.39 (95% CI 3.75 to 5.14; p < 0.001) on days 1 to 2 after discharge and 2.09 (95% CI 1.92 to 2.28; p < 0.001) on days 3 to 14. 11,629/13,609 deaths (85.5%) did not occur close to a hospital admission, and the remaining 656/13,609 deaths (4.8%) occurred in hospital following admission due to drug poisoning. Risk was greater for patients discharged from psychiatric admissions, those who left the hospital against medical advice, and those leaving the hospital after admissions of 7 days or more. The main limitation of the method is that it does not control for time-varying health or drug use within individuals; therefore, hospital admissions coinciding with high-risk periods may in part explain the results.ConclusionsDischarge from the hospital is associated with an acute increase in the risk of opioid-related death, and 1 in 14 opioid-related deaths in England happens in the 2 weeks after the hospital discharge. This supports interventions that prevent early discharge and improve linkage with community drug treatment and harm reduction services.

In a case-crossover study, Dan Lewer and coauthors investigate factors associated with fatal opioid overdoses during and shortly after hospital admissions in England.     

Estimation of bird distribution based on ring re‐encounters: precision and bias of the division coefficient and its relation to multi‐state models

Capsule The division coefficient is an estimate of the proportion of ringed birds migrating to different destination areas taking into account area‐specific re‐encounter probabilities.

Aims To explore precision and bias of the division coefficient method by a simulation study and to compare the approach with multi‐state models.

Methods In a simulation study true and estimated division coefficients were compared. The division coefficient method was mathematically compared with the multi‐state model.

Results The estimated division coefficients seemed to be unbiased if the assumptions were met. The precision decreased if the bird distribution became similar in both bird groups and when difference between area‐specific re‐encounter probabilities increased. A bootstrap method to assess precision is presented. The estimates from the division coefficient method equal the maximum likelihood estimates in a multi‐state model including only one time interval.

Conclusion Before applying the division coefficient method or a multi‐state model to real data a simulation study should be conducted in order to explore the behaviour of parameter estimation. The division coefficient method with the bootstrap confidence intervals is an easy alternative to a multi‐state model with one time interval when the bird distribution between destination areas (e.g. migratory connectivity) alone is of interest.     

Vaccination against SARS-CoV-2 and risk of hospital admission and death among infected cancer patients: A population-based study in northern Italy

BackgroundThe risks of hospital admission for COVID-19-related conditions and all-cause death of SARS-CoV-2 infected cancer patients were investigated according to vaccination status.MethodsA population-based cohort study was carried out on 9754 infected cancer patients enrolled from January 1, 2021 to June 30, 2022. Subdistribution hazard ratio (SHRs) or hazard ratios (HRs) with 95 % confidence intervals (CI), adjusted for sex, age, comorbidity index, and time since cancer incidence, were computed to assess the risk of COVID-19 hospital admission or death of unvaccinated vs. patients with at least one dose of vaccine (i.e., vaccinated).Results2485 unvaccinated patients (25.5 %) were at a 2.57 elevated risk of hospital admission (95 % CI: 2.13–2.87) and at a 3.50 elevated risk of death (95 % CI: 3.19–3.85), as compared to vaccinated patients. Significantly elevated hospitalizations and death risks emerged for both sexes, across all age groups and time elapsed since cancer diagnosis. For unvaccinated patients, SHRs for hospitalization were particularly elevated in those with solid tumors (SHR = 2.69 vs. 1.66 in patients with hematologic tumors) while HRs for the risk of death were homogeneously distributed. As compared to boosted patients, SHRs for hospitalization and HRs for death increased with decreasing number of doses.ConclusionsStudy findings stress the importance of SARS-CoV-2 vaccines to reduce hospital admission and death risk in cancer patients.     

Reduction in mortality after inappropriate early discharge from intensive care unit: logistic regression triage model

ObjectiveTo develop a predictive model to triage patients for discharge from intensive care units to reduce mortality after discharge.DesignLogistic regression analyses and modelling of data from patients who were discharged from intensive care units.SettingGuy''s hospital intensive care unit and 19 other UK intensive care units from 1989 to 1998.Participants5475 patients for the development of the model and 8449 for validation.ResultsMortality after discharge from intensive care was up to 12.4%. The triage model identified patients at risk from death on the ward with a sensitivity of 65.5% and specificity of 87.6%, and an area under the receiver operating curve of 0.86. Variables in the model were age, end stage disease, length of stay in unit, cardiothoracic surgery, and physiology. In the validation dataset the 34% of the patients identified as at risk had a discharge mortality of 25% compared with a 4% mortality among those not at risk.ConclusionsThe discharge mortality of at risk patients may be reduced by 39% if they remain in intensive care units for another 48 hours. The discharge triage model to identify patients at risk from too early and inappropriate discharge from intensive care may help doctors to make the difficult clinical decision of whom to discharge to make room for a patient requiring urgent admission to the unit. If confirmed, this study has implications on the provision of resources.

What is already known on this topic

In the United Kingdom, the mortality of patients who die on the ward after discharge from intensive care is unacceptably high (9% to 27%)Indirect evidence has shown that this is due to too early and inappropriate discharge from intensive care that has increased over the past 10 years

What this study adds

A triage model identifies patients at risk from inappropriate discharge from intensive careMortality after discharge from intensive care may be reduced by 39% if these patients were to stay in intensive care for another 48 hoursAn estimated 16% more beds are required if mortality after discharge from intensive care is to be reduced     

胰腺癌患者循环肿瘤细胞及TLR4、TLR9、myd88的表达水平与其化疗效果及转移、复发的关系

目的:探讨胰腺癌患者循环肿瘤细胞(CTC)中Toll样受体4(TLR4)、Toll样受体9(TLR9)、髓样分化因子88(myd88)的表达水平与患者化疗效果及转移、复发的关系。方法:将我院2015年6月-2016年6月收治并确诊的48例胰腺癌患者作为试验组,收集患者循环肿瘤细胞(CTC),检测其TLR4、TLR9、myd88信号表达情况,探讨其TLR4、TLR9、myd88信号表达水平与患者化疗效果及转移、复发的关系。结果:48例胰腺癌患者检出CTC 35例,检出率为72.9%。胰腺癌死亡、转移、复发患者TLR4、TLR9、myd88表达水平分别高于其存活、未转移、未复发患者,组间具有统计学差异(P0.05)。胰腺癌化疗效果CR患者TLR4、TLR9、myd88表达水平显著低于其化疗效果PR、SD、PD患者,且四组间差异具有统计学意义(P0.05);TLR4、TLR9、myd88表达水平与被膜受侵犯、淋巴结转移、肿瘤大小、CA199水平呈正相关(P0.05)。结论:胰腺癌患者CTC中TLRs/myd88信号表达水平与患者化疗效果及转移、复发密切相关。     

Inpatient to Outpatient Transfer of Diabetes Care: Planning for an Effective Hospital Discharge

ObjectiveTo review data on diabetes discharge planning, provide a definition of an effective diabetes discharge, and summarize one institution’s diabetes discharge planning processes in a teaching hospital.MethodsWe performed a MEDLINE search of the English-language literature published between January 1998 and December 2007 for articles related to the inpatient to outpatient transition of diabetes care. Regulatory guidelines about discharge planning were reviewed. We also analyzed our institution’s procedures regarding hospital discharge.ResultsWe define an effective diabetes discharge as one where the patient has received the necessary skills training and been provided with a clear and understandable postdischarge plan for diabetes care that has been clearly documented and is accessible by the patient’s outpatient health care team. Diabetes is one of the most common conditions managed in the hospital, yet how to transition a patient with diabetes to the outpatient setting is understudied, and the outcome of patients with diabetes after discharge is unknown. Strategies that can be used to ensure an effective diabetes discharge are early identification of patients in need of education, implementation of a clinical pathway, and clear instructions about medications and follow-up appointments at the time of discharge.ConclusionsEffective transfer of care from the inpatient to the outpatient setting remains a priority in the United States. Studies are needed to better define how best to ensure that patients with diabetes are successfully transitioned to ambulatory care. (Endocr Pract. 2009;15:263-269)     

Multiple causes of death and the epidemiological transition in American Samoa

Abstract

Multiple‐cause mortality data were used to examine changing patterns of mortality between 1950 and 1979 in American Samoa. This period coincided with a transition from infectious to chronic diseases as the primary causes of death. The available data indicate that as mortality rates from infections declined, the first chronic disease to increase in frequency was cancer. The absence of a lag period suggests that increased cancer mortality may be a consequence of life extension in the presence of modernization. In contrast, mortality rates from cardiovascular diseases tended to increase only after a lag period. As mortality from infections declined, ischemic heart disease replaced infections as the leading cause of death, in either a total‐mentions or an underlying‐cause model of mortality. The transition to degenerative disease mortality in American Samoa was neither as rapid nor as simple as a tabulation by underlying cause of death indicates. Patterns of change were interrelated.     

Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: A cohort study using linked primary care,secondary care,and death registration data in the OpenSAFELY platform

BackgroundThere is concern about medium to long-term adverse outcomes following acute Coronavirus Disease 2019 (COVID-19), but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation.Methods and findingsWith the approval of NHS-England, we conducted a cohort study, using linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February to December 2020) and surviving at least 1 week, and (i) demographically matched controls from the 2019 general population; and (ii) people discharged from influenza hospitalisation in 2017 to 2019. We used Cox regression adjusted for age, sex, ethnicity, obesity, smoking status, deprivation, and comorbidities considered potential risk factors for severe COVID-19 outcomes.We included 24,673 postdischarge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls, followed for ≤315 days. COVID-19 patients had median age of 66 years, 13,733 (56%) were male, and 19,061 (77%) were of white ethnicity. Overall risk of hospitalisation or death (30,968 events) was higher in the COVID-19 group than general population controls (fully adjusted hazard ratio [aHR] 2.22, 2.14 to 2.30, p < 0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, p = 0.004). All-cause mortality (7,439 events) was highest in the COVID-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls [p < 0.001] and 1.74, 1.61 to 1.88 versus influenza controls [p < 0.001]). Risks for cause-specific outcomes were higher in COVID-19 survivors than in general population controls and largely similar or lower in COVID-19 compared with influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, p < 0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, p = 0.039); in particular, COVID-19 survivors with preexisting dementia had higher risk of dementia hospitalisation or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, p = 0.002). Limitations of our study were that reasons for hospitalisation or death may have been misclassified in some cases due to inconsistent use of codes, and we did not have data to distinguish COVID-19 variants.ConclusionsIn this study, we observed that people discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations, but COVID-19 patients had higher risks of all-cause mortality, readmission or death due to the initial infection, and dementia death, highlighting the importance of postdischarge monitoring.

Krishnan Bhaskaran and co-workers study health outcomes after admission with COVID-19 and subsequent discharge.     

On the significance of Tim-3 expression in pancreatic cancer

ObjectiveWe aim to explore the connection between Tim-3 expression in both cancerous pancreatic and pericarcinous tissues and the clinicopathological features of pancreatic cancer. We will also preliminarily assess the role and significance of Tim-3 in the diagnosis, treatment, and prognosis of pancreatic cancer.MethodsCancerous pancreatic and pericarcinous tissues from 50 patients with pancreatic cancer and six healthy pancreatic tissues were collected from the pathological specimens of traumatic patients to distinguish Tim-3 expression using immunohistochemistry. Tim-3 expression was observed to be correlated with cell invasion, metastasis, and recurrence of pancreatic cancer.Results1. For the immunohistochemical method, Tim-3 expression in pancreatic cancer tissues was observed to be elevated and statistically significant (P < .01) compared to pericarcinous and normal pancreatic tissues. No statistically significant difference (P > .05) was observed between Tim-3 expression in pericarcinous and normal pancreatic tissues. 2. While Tim-3 expression was observed to be closely related to the history of smoking, fasting blood glucose, tumor size, TNM stage, it was not observed to be related to gender, age, tumor location, pathological type, and degree of tumor differentiation.Conclusion1. Tim-3 expression in pancreatic cancer tissues was high. 2. The high Tim-3 expression in pancreatic cancer tissues may be closely related to cell invasion, metastasis, and the recurrence of pancreatic cancer.     

Routes to diagnosis and the association with the prognosis in patients with cancer – A nationwide register-based cohort study in Denmark

BackgroundThe prognosis of cancer is related to how the cancer is identified, and where in the healthcare system the patient presents, i.e. routes to diagnosis (RtD). We aimed to describe the RtD for patients diagnosed with cancer in Denmark by using routinely collected register-based data and to investigate the association between RtD and prognosis measured as one-year all-cause mortality.MethodsWe conducted a population-based national cohort study by linking routinely collected Danish registry data. We categorised each patient into one of eight specified RtD based on an algorithm using a stepwise logic decision process. We described the proportions of patients with cancer diagnosed by different RtD. We examined associations between RtD and one-year all-cause mortality using logistic regression models adjusting for sex, age, cancer type, year of diagnosis, region of residence, and comorbidity.ResultsWe included 144,635 cancers diagnosed in 139,023 patients in 2014–2017. The most common RtD were cancer patient pathway from primary care (45.9 %), cancer patient pathway from secondary care (20.0 %), unplanned hospital admission (15.8 %), and population-based screening (7.5 %). The one-year mortality ranged from 1.4 % in screened patients to 53.0 % in patients diagnosed through unplanned hospital admission. Patients with an unplanned admission were more likely to die within the first year after diagnosis (OR = 3.38 (95 %CI: 3.24–3.52)) compared to patients diagnosed through the cancer patient pathway from primary care.ConclusionThe majority of cancer patients were diagnosed through a cancer patient pathway. The RtD were associated with the prognosis, and the prognosis was worst in patients diagnosed through unplanned admission. The study suggests that linking routinely collected registry data could enable a national framework for RtD, which could serve to identify variations across patient-, health-, and system-related and healthcare factors. This information could be used in future research investigating markers for monitoring purposes.     

Autophagy in pancreatic cancer: An emerging mechanism of cell death

Pancreatic cancer, the fourth leading cause of cancer-related death in the United States, is resistant to current chemotherapies. Therefore, identification of different pathways of cell death is important to develop novel therapeutics. Our previous study has shown that triptolide, a diterpene triepoxide, inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo. However, the mechanism by which triptolide kills pancreatic cancer cells was not known, hence, this study aimed at elucidating it. Our study reveals that triptolide kills diverse types of pancreatic cancer cells by two different pathways; it induces caspase-dependent apoptotic death in some cell lines and death via a caspase-independent autophagic pathway in the other cell lines tested. Triptolide-induced autophagy requires autophagy-specific genes, atg5 or beclin 1 and its inhibition results in cell death via the apoptotic pathway, whereas inhibition of both autophagy and apoptosis rescues triptolide-mediated cell death. Our study shows for the first time that induction of autophagy by triptolide has a pro-death role in pancreatic cancer cells. Since triptolide kills diverse pancreatic cancer cells by different mechanisms, it makes an attractive chemotherapeutic agent for future use against a broad spectrum of pancreatic cancers.Key words: pancreatic cancer, triptolide, apoptosis, caspase-3Pancreatic adenocarcinoma is one of the most lethal human malignancies. It is the fourth leading cause of cancer-related death in the United States. The five-year survival rate for pancreatic cancer is estimated to be <5% due to its aggressive growth, metastasis and resistance to radiation and most systemic chemotherapies. Hence, efforts are ongoing to understand the pathobiology of pancreatic cancer to develop innovative and effective therapies against it. A promising candidate for future therapeutic use against pancreatic cancer is a diterpene triepoxide, triptolide. Our previous studies show that triptolide inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo. Since the mechanism by which triptolide kills pancreatic cancer cells was not known, we decided to elucidate it.The K-ras, p53, p16 and DPC4 genes are the most frequently altered genes in pancreatic adenocarcinoma. In this study we have used diverse pancreatic cancer cell lines, MiaPaCa-2, Capan-1, S2-013 and S2-VP10 cells, which have mutations in all the above-mentioned genes and BxPC-3 and Hs766T cells, which have mutations in the p53, p16 and DPC4 genes, but have a wild-type K-ras gene. The treatment of all the cell lines with triptolide results in a significant time- and dose-dependent decrease in cell viability, independent of cell cycle arrest. After treatment with triptolide, only MiaPaCa-2, Capan-1 and BxPC-3 cells show an increase in the apoptosis parameters: cytochrome c release from mitochondria into the cytosol, caspase-3 activation and phosphatidylserine externalization. In contrast to this, S2-013, S2-VP10 and Hs766T cells show an induction of autophagy: an increase in LC3-II levels (by immunoblotting and immufluorescence), increase in acridine orange-positive cells, inhibition of the PtdIns3K/Akt/mTOR pathway and induction of the ERK1/2 pathway. Also, none of the cell lines tested show necrosis as evidenced by the absence of the release of lactate dehydrogenase. These results indicate that triptolide induces apoptosis in MiaPaCa-2, Capan-1 and BxPC-3 cells, whereas it induces autophagy in S2-013, S2-VP10 and Hs766T cells.Since the role of autophagy in cancer was controversial we investigated whether triptolide-induced autophagy has a prosurvival or a pro-death role. As autophagy-associated cell death is independent of caspase-3, we tested the effect of triptolide on pancreatic cancer cells in the absence of caspase-3. Treatment of cells with triptolide post-caspase-3 knockdown shows a significant rescue of cell viability only in MiaPaCa-2, but not S2-013 or S2-VP10 cells. This indicates that in contrast to MiaPaCa-2, triptolide-mediated cell death in S2-013 and S2-VP10 cells is independent of caspase-3. Next, we tested the role of autophagy in triptolide-mediated cell death in pancreatic cancer cells. In spite of a knockdown of autophagy-specific genes (atg5 and beclin 1), treatment of S2-013 and S2-VP10 cells with triptolide show a significant decline in cell viability, which is comparable to the cells treated with triptolide in the presence of autophagy genes. Subsequently we show that death in the absence of autophagy-specific genes is due to the utilization of an alternate cell death pathway, apoptosis. Furthermore, in the absence of both autophagy-specific and apoptosis-specific genes, triptolide-mediated cell death is rescued in S2-013 and S2-VP10 cells. Thus, these results confirm that triptolide-induced autophagy has a pro-death role in S2-013 and S2-VP10 cells and that these cells do not have a defect in the apoptotic machinery; however, they respond to triptolide by activating the autophagic pathway instead of the apoptotic pathway. Our studies also reveal the presence of a crosstalk between the two cell death pathways, apoptosis and autophagy, in pancreatic cancer cells.In conclusion, our study shows for the first time that triptolide induces autophagy in pancreatic cancer cells. It sheds light on the fundamental question as to whether autophagy is protective or causes cell death, proving convincingly that induction of autophagy causes cell death of some pancreatic cancer cells. Although a basal level of autophagy is necessary to maintain cellular homeostasis, its prosurvival role can be switched into a cell death mechanism if the amplitude of autophagy increases above a threshold level which is incompatible with viability, as seen in S2-013, S2-VP10 and Hs766T cells after triptolide treatment. Furthermore, there exists a crosstalk between apoptosis and autophagy in S2-013 and S2-VP10 cells; either both pathways function independently to kill the cells, with autophagy being the preferred pathway or autophagy antagonizes apoptosis and hence apoptosis is seen only after inhibiting autophagy. Although there is no direct correlation between the selection of cell death pathway in response to triptolide and the genotype of the cell lines, the choice of autophagic cell death pathway could depend on the metastatic potential of the cells; S2-013, S2-VP10 and Hs766T cell lines being more metastatic than the others, which merits further investigation. In conclusion, the ability of triptolide to induce cell death in diverse pancreatic cancer cells by either mechanism makes it an attractive chemotherapeutic agent against a broad spectrum of pancreatic cancers.     

Autophagy in pancreatic cancer

Pancreatic cancer, the fourth leading cause of cancer-related death in the United States, is resistant to current chemotherapies. Therefore, identification of different pathways of cell death is important to develop novel therapeutics. Our previous study has shown that triptolide, a diterpene triepoxide, inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo. However, the mechanism by which triptolide kills pancreatic cancer cells was not known, hence, this study aimed at elucidating it. Our study reveals that triptolide kills diverse types of pancreatic cancer cells by two different pathways; it induces caspase-dependent apoptotic death in some cell lines and death via a caspase-independent autophagic pathway in the other cell lines tested. Triptolide-induced autophagy requires autophagy-specific genes, atg5 or beclin 1, and its inhibition results in cell death via the apoptotic pathway, whereas inhibition of both autophagy and apoptosis rescues triptolide-mediated cell death. Our study shows for the first time that induction of autophagy by triptolide has a pro-death role in pancreatic cancer cells. Since triptolide kills diverse pancreatic cancer cells by different mechanisms, it makes an attractive chemotherapeutic agent for future use against a broad spectrum of pancreatic cancers.     

低剂量灌注CT成像诊断胰腺癌的研究进展

随着MSCT的不断发展以及检查技术的不断完善,胰腺疾病的诊断率也不断进步。CT可以对胰腺进行普通平扫、多期增强扫描及CT灌注扫描(CTPI)。其中,普通平扫及增强扫描对小的胰腺癌病灶诊断率较低;普通灌注扫描可以通过监测胰腺组织血流动力学评价胰腺功能,对于早期胰腺癌的诊断率较高,但辐射剂量也较高,因此对患者的远期影响较大。因此,在满足对胰腺癌疾病诊断条件的前提下,减少CT扫描对患者的辐射剂量是目前临床研究的热点。灌注扫描通过监测患者血流量(BF)、血容量(BV)对正常胰腺及胰腺癌病灶进行观察,能够在减少辐射剂量的同时获得灌注数据,从而提供更多的诊断信息,进而满足临床诊断的要求。     

Inpatient Hyperglycemia and Transitions of Care: A Systematic Review

ObjectiveThe transition of diabetes care from home to hospital, within the hospital, and upon discharge is fraught with gaps that can adversely affect patient safety and length of stay. We aimed to highlight the variability in care during these transitions and point out areas where research is needed.MethodsA PubMed search was performed with a combination of search terms that pertained to diabetes, hyperglycemia, hospitalization, locations in the hospital, discharge to home or a nursing facility, and diabetes medications. Studies with at least 50 patients that were written in the English language were included.ResultsWith the exception of transitioning from intravenous insulin infusion to subcutaneous insulin and perhaps admission to the regular floors, few studies pointedly focused on transitions of care, leading us to extrapolate recommendations based on data from disparate areas of care in the hospital. There is evidence at every stage of care, starting from the entry into the hospital and ending with discharge home or to a facility, that patients benefit from having protocols in place guiding overall care.ConclusionPockets of care exist in hospitals where methods of effective diabetes management have been studied and implemented. However, there is no sustained continuum of care. Protocols and care teams that follow patients from one physical location to the other may result in improved clinical outcomes during and following a hospital stay.