Surgery for hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetically determined cardiac disease characterised by otherwise unexplained myocardial hypertrophy of the left ventricle, and may result in left ventricular outflow tract obstruction. It is the most common cause of sudden cardiac death in young adults due to arrhythmias. Septal myectomy is a surgical treatment for HCM with moderate to severe outflow tract obstruction, and is indicated for patients with severe symptoms refractory to medical therapy. The surgical approach involves obtaining access to the interventricular septum via transaortic, transapical or transmitral approaches, and excising a portion of the hypertrophied myocardium to relieve the outflow tract obstruction. Large, contemporary series from centres experienced in septal myectomy patients have demonstrated a low early mortality of <2 %, excellent long-term survival that matches the general population, and durable relief of symptoms.     

The Effects of Intra-Aortic Balloon Pumps on Mortality in Patients Undergoing High-Risk Coronary Revascularization: A Meta-Analysis of Randomized Controlled Trials of Coronary Artery Bypass Grafting and Stenting Era

Background

Intra-aortic balloon pumps (IABP) have generally been used for patients undergoing high-risk mechanical coronary revascularization. However, there is still insufficient evidence to determine whether they can improve outcomes in reperfusion therapy patients, mainly by percutaneous coronary intervention (PCI) with stenting or coronary artery bypass graft (CABG). This study was designed to determine the difference between high-risk mechanical coronary revascularization with and without IABPs on mortality, by performing a meta-analysis on randomized controlled trials of the current era.

Methods

Pubmed and Embase databases were searched from inception to May 2015. Unpublished data were obtained from the investigators. Randomized clinical trials of IABP and non-IABP in high-risk coronary revascularization procedures (PCI or CABG) were included. In the case of PCI procedures, stents should be used in more than 80% of patients. Numbers of events at the short-term and long-term follow-up were extracted.

Results

A total of 12 randomized trials enrolling 2155 patients were included. IABPs did not significantly decrease short-term mortality (relative risk (RR) 0.66; 95% CI, 0.42–1.01), or long-term mortality (RR 0.79; 95% CI, 0.47–1.35), with low heterogeneity across the studies. The findings remained stable in patients with acute myocardial infarction with or without cardiogenic shock. But in high-risk CABG patients, IABP was associated with reduced mortality (71 events in 846 patients; RR 0.40; 95%CI 0.25–0.67).

Conclusion

In patients undergoing high-risk coronary revascularization, IABP did not significantly decrease mortality. But high-risk CABG patients may be benefit from IABP. Rigorous criteria should be applied to the use of IABPs.     

Tiotropium might improve survival in subjects with COPD at high risk of mortality

Background

Inhaled therapies reduce risk of chronic obstructive pulmonary disease (COPD) exacerbations, but their effect on mortality is less well established. We hypothesized that heterogeneity in baseline mortality risk influenced the results of drug trials assessing mortality in COPD.

Methods

The 5706 patients with COPD from the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) study that had complete clinical information for variables associated with mortality (age, forced expiratory volume in 1 s, St George’s Respiratory Questionnaire, pack-years and body mass index) were classified by cluster analysis. Baseline risk of mortality between clusters, and impact of tiotropium were evaluated during the 4-yr follow up.

Results

Four clusters were identified, including low-risk (low mortality rate) patients (n = 2339; 41%; cluster 2), and high-risk patients (n = 1022; 18%; cluster 3), who had a 2.6- and a six-fold increase in all-cause and respiratory mortality compared with cluster 2, respectively. Tiotropium reduced exacerbations in all clusters, and reduced hospitalizations in high-risk patients (p < 0.05). The beneficial effect of tiotropium on all-cause mortality in the overall population (hazard ratio, 0.87; 95% confidence interval, 0.75–1.00, p = 0.054) was explained by a 21% reduction in cluster 3 (p = 0.07), with no effect in other clusters.

Conclusions

Large variations in baseline risks of mortality existed among patients in the UPLIFT® study. Inclusion of numerous low-risk patients may have reduced the ability to show beneficial effect on mortality. Future clinical trials should consider selective inclusion of high-risk patients.     

Clinical findings,early endoscopy,and multivariate analysis in patients bleeding from the upper gastrointestinal tract.

A simple system has been developed to identify patients with upper gastrointestinal tract haemorrhage who run a high risk of continued bleeding or rebleeding. The system is based on six items of patient data available at or soon after arrival in hospital. It was evaluated in a prospective study of 66 patients with upper gastrointestinal tract haemorrhage. Over half of the patients classified by the system into a high-risk category either continued bleeding or rebled after apparent cessation (as against one out of 33 patients in the low-risk category). The high-rish group also had a higher mortality (21%) than those in the low-risk group (nil). The addition or subtraction of early endoscopic findings made little difference to the accuracy of prognosis.     

Construction of a prognostic model for non-small-cell lung cancer based on ferroptosis-related genes

We wished to construct a prognostic model based on ferroptosis-related genes and to simultaneously evaluate the performance of the prognostic model and analyze differences between high-risk and low-risk groups at all levels. The gene-expression profiles and relevant clinical data of patients with non-small-cell lung cancer (NSCLC) were downloaded from public databases. Differentially expressed genes (DEGs) were obtained by analyzing differences between cancer tissues and paracancerous tissues, and common genes between DEGs and ferroptosis-related genes were identified as candidate ferroptosis-related genes. Next, a risk-score model was constructed using univariate Cox analysis and least absolute shrinkage and selection operator (Lasso) analysis. According to the median risk score, samples were divided into high-risk and low-risk groups, and a series of bioinformatics analyses were conducted to verify the predictive ability of the model. Single-sample gene set enrichment analysis (ssGSEA) was used to investigate differences in immune status between high-risk and low-risk groups, and differences in gene mutations between the two groups were investigated. A risk-score model was constructed based on 21 ferroptosis-related genes. A Kaplan–Meier curve and receiver operating characteristic curve showed that the model had good prediction ability. Univariate and multivariate Cox analyses revealed that ferroptosis-related genes associated with the prognosis may be used as independent prognostic factors for the overall survival time of NSCLC patients. The pathways enriched with DEGs in low-risk and high-risk groups were analyzed, and the enriched pathways were correlated significantly with immunosuppressive status.     

Adjuvant therapy after radical surgery of cervical cancer: Zagreb experience

The results of the analysis of the treatment of 72 patients with carcinoma of the uterine cervix are presented. Seventy-two patients with Stage IB1 carcinoma of the cervix underwent a radical hysterectomy and pelvic lymphadenectomy. The low-risk group includes the patients without unfavourable prognostic factors that were treated by surgery alone. The high-risk group included women with pelvic node metastases, clinical tumour size greater than 3.0 cm, depth of stromal invasion greater than 1/3 of the cervical wall, Grade 3 tumours and the presence of lympho-vascular space involvement. High-risk patients received whole pelvic radiotherapy between two and four weeks following surgery. Thirty-four patients (47.2%) were in the low-risk group and thirty-eight patients (52.8%) were in the high-risk group. Locoregional recurrences were diagnosed in three cases (8.8%) in the surgery group and in four patients (10.5 %) assigned to postoperative radiotherapy. The incidence of distant metastases was 2.9% in the group treated by surgery alone and 5.3% in the group treated by surgery and radiotherapy. Overall survival at five years was 91.2% in the low-risk group and 89.5% in the high-risk group of patients. Five-year overall survival, locoregional and distant metastases were similar in the low-risk and high-risk groups of patients, which emphasizes the value of whole pelvic radiation in patients with one or more unfavourable prognostic factors after radical surgery in Stage IB1 cervical cancer     

IABP在危重症冠状动脉旁路移植术围手术期的应用

目的：探讨危重症冠状动脉旁路移植术（CABG）患者围手术期应用主动脉球囊反搏（IABP）疗效。方法：回顾性分析2008年1月至2010年9月40例应用IABP治疗的危重症CABG患者围手术期资料。结果：术前安置IABP 19例,术中安置IABP 10例,术后安置IABP11例。平均IABP辅助时间98.6±48.2小时。32例患者治愈出院,死亡8例,死亡率20.0%。术前安置者死亡率为21.1%,若除外机械并发症原因则死亡率为10.5%;术中安置者死亡率为20.0%;术后安置者死亡率为18.2%。5例出现血小板减少症;1例出现肠系膜动脉栓塞。结论：IABP是一种安全有效的循环辅助方法,积极应用可以明显提高危重症CABG的治疗效果。     

IABP在危重症冠状动脉旁路移植术围手术期的应用

目的:探讨危重症冠状动脉旁路移植术(CABG)患者围手术期应用主动脉球囊反搏(IABP)疗效。方法:回顾性分析2008年1月至2010年9月40例应用IABP治疗的危重症CABG患者围手术期资料。结果:术前安置IABP 19例,术中安置IABP 10例,术后安置IABP11例。平均IABP辅助时间98.6±48.2小时。32例患者治愈出院,死亡8例,死亡率20.0%。术前安置者死亡率为21.1%,若除外机械并发症原因则死亡率为10.5%;术中安置者死亡率为20.0%;术后安置者死亡率为18.2%。5例出现血小板减少症;1例出现肠系膜动脉栓塞。结论:IABP是一种安全有效的循环辅助方法,积极应用可以明显提高危重症CABG的治疗效果。     

Anthropogenic risk increases night-time activities and associations in African elephants (Loxodonta africana) in the Ruaha-Rungwa ecosystem,Tanzania

Elephants face diverse threats from human activities and use temporal and social strategies to reduce human-induced mortality risk. We used data from camera trap surveys in 2018–2019 (n = 1625 independent detection events from 11,751 sampling days) to investigate elephant responses to anthropogenic risk in the Ruaha-Rungwa ecosystem, Tanzania. The study was conducted in one low-risk and three high-risk sites using 26–40 paired camera trap stations per site. Risk influenced the active periods, use of roads and water sources, social associations and behaviour of elephants. Elephants demonstrated significantly more night-time and reduced daytime activity in the high-risk sites relative to the low-risk site. This higher night-time activity in the high-risk sites was observed for both males and females, though it was more pronounced for cow–calf groups than lone males. Foraging events and use of water sources were more frequent at night in the high-risk sites. Elephants used roads as movement routes in the low-risk site but avoided roads in the high-risk sites. Males were significantly more likely to associate with other males and cow–calf groups in the high-risk sites. Fewer occurrences of relaxed behaviours were observed in the high-risk sites compared to the low-risk site. We discuss the potential implications of our findings for elephant survival and reproduction.     

MR-proADM and MR-proANP levels in patients with acute pulmonary embolism

BackgroundThe aim of this study was to determine levels of Mid-regional Pro-adrenomedullin (MR-proADM) and Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) in patients with acute pulmonary embolism (PE), the relationship between these parameters and the risk classification in addition to determining the relationship between 1and 3month mortality.Methods82 PE patients and 50 healthy control subjects were included in the study. Blood samples for Mr-proANP and Mr-proADM were obtained from the subjects prior to the treatment. Risk stratification was determined according to sPESI (Simplified Pulmonary Embolism Severity Index). Following these initial measurements, cases with PE were assessed in terms of all causative and PE related mortalities.ResultsThe mean serum Mr-proANP and Mr-proADM levels in acute PE patients were found to be statistically higher compared to the control group (p < 0.001, p < 0.01; respectively) and statistically significantly higher in high-risk patients than low-risk patients (p < 0.01, p < 0.05; respectively). No statistical difference was determined in high-risk patients in case of sPESI compared to low-risk patients while hospital mortality rates were higher. It was determined that the hospital mortality rate in cases with Mr-proANP ≥ 123.30 pmol/L and the total 3-month mortality rate in cases with Mr-proADM ≥ 152.2 pg/mL showed a statistically significant increase.ConclusionsThis study showed that Mr-proANP and MRproADM may be an important biochemical marker for determining high-risk cases and predicting the mortality in PE patients and we believe that these results should be supported by further and extensive studies.     

High-Risk But Not Low-Risk HPV E2 Proteins Bind to the APC Activators Cdh1 and Cdc20 and Cause Genomic Instability

Human papillomaviruses (HPVs) from the high-risk group are associated with cervicalcancer, in contrast to HPVs from the low-risk group which are associated with benignlesions. Here, we show that high-risk, but not low-risk HPV E2 proteins, promote amitotic block, often followed by metaphase-specific apoptosis, and which is independentof the viral oncogenes E6 and E7. High-risk HPV E2-expressing cells also showpolyploidy, chromosomal mis-segregation and centrosome amplification leading togenomic instability. We link these defects to a specific and unusually strong interactionbetween high-risk E2 and both Cdc20 and Cdh1, two activators of the AnaphasePromoting Complex (APC), abnormal localization of Cdh1, and accumulation of APCsubstrates like cyclin B, in vivo. The finding that high-risk, but not low-risk HPV E2proteins, induce genomic instability, raises the intriguing possibility that E2 proteinsplay a role in the oncogenic potential of high-risk papillomaviruses.     

Glasgow-Blatchford和Rockall评分系统对上消化道出血患者治疗的指导作用比较

目的：比较Glasgow-Blatchford和Rockall评分系统对上消化道出血患者治疗的指导作用。方法：回顾分析我院收治的上消化道出血病人共366例,详细记录每一位入组患者的临床表现、生命体征、实验室检查结果,根据Glasgow-Blatchford和Rockall评分系统的规则计算每一位患者的危险分值,并依据其分值将其分为低危组和高危组（Glasgow-Blatchford≥1分,Rockall≥1分）。结果：366例上消化道出血患者有243位（66.4%）经过补液、抑酸等保守治疗后出血停止,并按照临床实际将其定义为低危患者,Glasgow-Blatchford评分为0的低危患者有63位（17.2%）,Rockall评分为0的低危患者有99人（27.0%）,参照临床治疗中实际的高低危患者,计算得到Rockall评分系统对高危患者诊断的敏感性为87.0%,而Glasgow-Blatchford评分系统对高危患者诊断的敏感性为100%。Glasgow-Blatchford评分系统对上消化道出血高危患者诊断的敏感性明显高于临床Rockall评分系统。结论：基于实验室检查和临床表现的Glasgow-Blatchford评分,是一种简单、有效的判断上消化道出血严重程度的评分系统,有助于临床医师选择正确的治疗方案。     

Application Of The American College Of Emergency Physicians (ACEP) Recommendations And a Risk Stratification Score (OESIL) For Patients With Syncope Admitted From The Emergency Department

Aims

The goals of this study were to apply the 2001 ACEP recommendations for admission to hospital after a syncopal event and to validate the OESIL risk stratification score, in patients with syncope admitted to a general internal medicine ward.

Methods

A retrospective study applied the 2001 ACEP recommendations and OESIL score to all the patients admitted from the emergency department to a general internal medicine ward with a diagnosis of syncope during a 12-month period. The patients were classified as meeting criteria for 2001 ACEP class B or C recommendations and OESIL score 0-1 (low-risk for a major cardiac event) or 2-4 (high-risk for a major cardiac event). The sensitivity and specificity of each group for predicting high-risk patients was calculated.

Results

After applying the 2001 ACEP recommendations to our population, 25% (19 patients) were classified as level B, whereas 68% of the patients were classified as Level C. Sensitivity for ACEP level B recommendations was 100% and specificity was 81%. The ACEP level C recommendations also had 100% sensitivity but markedly reduced specificity at 26%. An OESIL score of 0-1 points was calculated for 30.6% of the population, identifying them as low-risk. An OESIL score of 2-4 points was documented in the remaining 69.4% with a mortality risk of 20 % /year.

Conclusion

A significant proportion (30%) of patients presenting with syncope to a tertiary care University Hospital emergency department and admitted to an Internal Medicine ward were retrospectively classified as low-risk and could have potentially been managed as outpatients. Implementing current guidelines and clinical pathways for the management of syncope may improve this approach.     

Combined replacement of the ascending aorta and the aortic valve in 42 consecutive patients: A comparison of composite graft techniques and conventional techniques over one year

During 1978, 42 consecutive patients underwent simultaneous aortic valve and ascending aorta replacement in our institution. Seventy-one percent were at low risk despite a high incidence of dissection. Twenty-nine percent were high-risk patients requiring repeat or concomitant cardiac procedures, mostly on an emergency basis. Depending upon the extent of the disease at the aortic root, either of two surgical approaches was used: (1) conventional aortic valve and supracoronary ascending aorta replacement, with or without right coronary artery ostium reimplantation, or (2) insertion of a composite graft containing an aortic valve prosthesis, with reconstruction of both coronary arteries. Preservation of coronary ostia was possible in 85% of the patients, and composite grafts were used in 15%. The conventional method was associated with a higher percentage of survivors. This technique was found to be satisfactory unless severe dilatation or complete destruction of the aortic annulus made composite grafting necessary. The latter technique was associated with fewer re-explorations for postoperative hemorrhage. Both procedures were equally effective, resulting in an operative mortality of 10% in uncomplicated situations. Surgery appeared to offer the only chance of survival for the high-risk group, and half of these patients were salvaged.     

Distinguishing Low-Risk Luminal A Breast Cancer Subtypes with Ki-67 and p53 Is More Predictive of Long-Term Survival

Overexpression of p53 is the most frequent genetic alteration in breast cancer. Recently, many studies have shown that the expression of mutant p53 differs for each subtype of breast cancer and is associated with different prognoses. In this study, we aimed to determine the suitable cut-off value to predict the clinical outcome of p53 overexpression and its usefulness as a prognostic factor in each subtype of breast cancer, especially in luminal A breast cancer. Approval was granted by the Institutional Review Board of Samsung Medical Center. We analyzed a total of 7,739 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between Dec 1995 and Apr 2013. Luminal A subtype was defined as ER&PR + and HER2- and was further subclassified according to Ki-67 and p53 expression as follows: luminal A (Ki-67-,p53-), luminal A (Ki-67+, p53-), luminal A (Ki-67 -, p53+) and luminal A (Ki-67+, p53+). Low-risk luminal A subtype was defined as negative for both Ki-67 and p53 (luminal A [ki-67-, p53-]), and others subtypes were considered to be high-risk luminal A breast cancer. A cut-off value of 10% for p53 was a good predictor of clinical outcome in all patients and luminal A breast cancer patients. The prognostic role of p53 overexpression for OS and DFS was only significant in luminal A subtype. The combination of p53 and Ki-67 has been shown to have the best predictive power as calculated by the area under curve (AUC), especially for long-term overall survival. In this study, we have shown that overexpression of p53 and Ki-67 could be used to discriminate low-risk luminal A subtype in breast cancer. Therefore, using the combination of p53 and Ki-67 expression in discriminating low-risk luminal A breast cancer may improve the prognostic power and provide the greatest clinical utility.     

Current translational and clinical practices in hematopoietic cell and gene therapy

Clinical trials over the last 15 years have demonstrated that cell and gene therapies for cancer, monogenic and infectious disease are feasible and can lead to long-term benefit for patients. However, these trials have been limited to proof-of-principle and were conducted on modest numbers of patients or over long periods of time. In order for these studies to move towards standard practice and commercialization, scalable technologies for the isolation, ex vivo manipulation and delivery of these cells to patients must be developed. Additionally, regulatory strategies and clinical protocols for the collection, creation and delivery of cell products must be generated. In this article we review recent progress in hematopoietic cell and gene therapy, describe some of the current issues facing the field and discuss clinical, technical and regulatory approaches used to navigate the road to product development.     

Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

Objective

Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status.

Methods

This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK.

Results

Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively.

Conclusions

Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.     

A Thirteen-Gene Expression Signature Predicts Survival of Patients with Pancreatic Cancer and Identifies New Genes of Interest

Background

Currently, prognostication for pancreatic ductal adenocarcinoma (PDAC) is based upon a coarse clinical staging system. Thus, more accurate prognostic tests are needed for PDAC patients to aid treatment decisions.

Methods and Findings

Affymetrix gene expression profiling was carried out on 15 human PDAC tumors and from the data we identified a 13-gene expression signature (risk score) that correlated with patient survival. The gene expression risk score was then independently validated using published gene expression data and survival data for an additional 101 patients with pancreatic cancer. Patients with high-risk scores had significantly higher risk of death compared to patients with low-risk scores (HR 2.27, p = 0.002). When the 13-gene score was combined with lymph node status the risk-score further discriminated the length of patient survival time (p<0.001). Patients with a high-risk score had poor survival independent of nodal status; however, nodal status increased predictability for survival in patients with a low-risk gene signature score (low-risk N1 vs. low-risk N0: HR = 2.0, p = 0.002). While AJCC stage correlated with patient survival (p = 0.03), the 13-gene score was superior at predicting survival. Of the 13 genes comprising the predictive model, four have been shown to be important in PDAC, six are unreported in PDAC but important in other cancers, and three are unreported in any cancer.

Conclusions

We identified a 13-gene expression signature that predicts survival of PDAC patients and could prove useful for making treatment decisions. This risk score should be evaluated prospectively in clinical trials for prognostication and for predicting response to chemotherapy. Investigation of new genes identified in our model may lead to novel therapeutic targets.     

Catheter-based transendocardial gene delivery for therapeutic myocardial angiogenesis

Currently it is unknown which is the most effective and safest delivery strategy for therapeutic myocardial angiogenesis. The enhancing effect of direct intramyocardial injection of angiogenic factors using either open-chest or catheter-based approaches on collateral function has been reported to occur in experimental models and among patients. This report reviews the rationale and current experience of using a catheter-based approach as a promising platform for proangiogenic intramyocardial gene delivery strategy.     

The senescence of Daphnia from risky and safe habitats

Evaluating life history in an ecological context is critical for understanding the diversity of life histories found in nature. Lifespan and senescence differ greatly among taxa, but their ecological context is not well known. Life history theory proposes that senescence is ultimately caused by a reduction of the effectiveness of natural selection as organisms age. A key prediction is that different levels of extrinsic mortality risk lead to the evolution of different senescence patterns. I quantified both mortality risk and investment in late-life fitness of Daphnia pulex-pulicaria , a common freshwater zooplankter. I found that Daphnia from high-risk pond habitats invest relatively little in late-life fitness, whereas those from low-risk lake habitats invest relatively more in late-life fitness. This suggests that ecological approaches can be useful for understanding senescence variation.