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// Hui Kong 1 , Ying Wu 1 , Mengou Zhu 2 , Changwen Zhai 3 , Jing Qian 1 , Xue Gao 4 , Shuyang Wang 1 , Yingyong Hou 3 , Shaohua Lu 3, * , Hongguang Zhu 1, 4, * 1 Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China 2 Harvard College, Harvard University, Cambridge, MA, USA 3 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China 4 Division of Surgical Pathology, Huashan Hospital, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Hongguang Zhu, email: hongguang_702@163.com Keywords: prognostic biomarker, long non-coding RNA, early stage colorectal cancer, liver metastasis, quantitative RT-PCR Received: December 06, 2015 Accepted: June 12, 2016 Published: July 06, 2016 ABSTRACT Liver metastasis is the primary cause of death for colorectal cancer (CRC) patients. To investigate the prognostic value of long non-coding RNAs (lncRNAs) on colorectal liver metastases, quantitative reverse-transcriptase PCR (quantitative RT-PCR) was performed on 15 lncRNAs in 51 stage IV CRC with liver metastases and 57 stage I/II CRC specimens. The expression levels of four lncRNAs (GAS5, H19, MEG3 and Yiya) were significantly different between liver metastases and primary tumors of stage IV CRC patients. Furthermore, the high expression levels of GAS5 and Yiya were significantly associated with future occurrence of liver metastases in early stage CRC patients. Kaplan-Meier analysis showed that the high expression levels of GAS5 or Yiya were correlated with poor prognosis of early stage CRC patients (p = 0.0206 and 0.0005 for GAS5 and Yiya, respectively). Yiya expression was proved to be an independent prognostic indicator of colorectal liver metastases in a multivariate analysis (relative risk = 10.7; p < 0.0001). Our study revealed that GAS5 and Yiya were promising prognostic biomarkers of liver metastases for early stage CRC patients.

// Hyo Song Kim 1 , Su-Jin Shin 2 , Seung-Hoon Beom 1 , Minkyu Jung 1 , Yoon Young Choi 3 , Taeil Son 3 , Hyoung-Il Kim 3 , Jae-Ho Cheong 3 , Woo Jin Hyung 3 , Sung Hoon Noh 3 , Hyunsoo Chung 4 , Jun Chul Park 4 , Sung Kwan Shin 4 , Sang Kil Lee 4 , Yong Chan Lee 4 , Woong Sub Koom 5 , Joon Seok Lim 6 , Hyun Cheol Chung 1 , Sun Young Rha 1 , Hyunki Kim 2 1 Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 2 Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea 3 Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea 4 Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 5 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea 6 Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea Correspondence to: Hyunki Kim, email: kimhyunki@yuhs.ac Sun Young Rha, email: rha7655@yuhs.ac Keywords: gastric cancer, molecular subtypes, immunohistochemistry, in-situ hybridization Received: April 04, 2016 Accepted: May 29, 2016 Published: June 16, 2016 ABSTRACT Gastric cancer (GC) is a leading cause of death. We aim to establish a clinically relevant assay that encompasses recent molecular classifications and provides useful clinical information in a large cohort of GC patients. A consecutive series of 438 GC patients that underwent palliative chemotherapy between 2014 and 2015 were assessed using 10 GC panels: EBER in-situ hybridization, immunohistochemistry for mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (RTKs; HER2, EGFR, and MET), PTEN, and p53 protein. With a median of one aberration, 3.3 % of samples analyzed were Epstein-Barr virus (EBV)-positive; 4.8%, MMR-deficient. RTKs were overexpressed in 218 patients; EGFR was most commonly overexpressed (39.9%), followed by HER2 (13.5%) and MET (12.1%). Furthermore, 2.5 % and 10.7 % of cases had simultaneous overexpression of three and two RTKs, respectively. p53 overexpression/null tumors were identified in 259 patients (59.1%), and PTEN loss was identified in 89 patients (20.3%). EBV-positivity was mutually exclusive with MMR-deficiency, predominantly identified in male patients, and these tumors were undifferentiated with proximal location. p53 mutant type was significantly found predominantly in the EBV-negative (60.6% vs 14.3%, P=0.001) and HER2-positive (78.0% vs 56.2%, P=0.002) groups. We described a molecular spectrum of distinct GC subtypes using clinically applicable assay. This assay will provide a convenient screening tool and facilitate the development of targeted agents in clinical trials.

BACKGROUND fat infiltration within and around skeletal muscle (i.e. myosteatosis) increases with ageing, is greater in African versus European ancestry men and is associated with poor health. Myosteatosis studies of mortality are lacking, particularly among African ancestry populations. METHODS in the Tobago Health study, a prospective longitudinal study, we evaluated the association of all-cause mortality with quantitative computed tomography (QCT) measured lower leg myosteatosis (intermuscular fat (IM fat) and muscle density) in 1,652 African ancestry men using Cox proportional hazards models. Date of death was abstracted from death certificates and/or proxy. RESULTS one hundred and twelve deaths occurred during follow-up (mean 5.9 years). In all men (age range 40-91 years), higher all-cause mortality was associated with greater IM fat (HR (95% CI) per SD: 1.29 (1.06-1.57)) and lower muscle density (HR (95% CI) per SD lower: 1.37 (1.08-1.75)) in fully adjusted models. Similar mortality hazard rates were seen in the subset of elderly men (aged ≥65 years) with greater IM fat (1.40 (1.11-1.78) or lower muscle density (1.66 (1.24-2.21)) in fully adjusted models. CONCLUSIONS our study identified a novel, independent association between myosteatosis and all-cause mortality in African ancestry men. Further studies are needed to establish whether this association is independent of other ectopic fat depots and to identify possible biological mechanisms underlying this relationship.

To investigate the rate and time trends of neonatal mortality from 1997 to 2014 in Shenyang, which were previously rarely reported upon by developing countries, data on 4719 neonatal deaths (0–28 days) and 970,583 live births from the Shenyang Women and Children Health Care Centre were analyzed. Neonatal mortality rates (per 1000 live births), percent change, and annual percent change (APC) were calculated. During the observation period, neonatal mortality in Shenyang significantly decreased by 7.04%, 8.33%, and 5.35% per year overall, in urban and rural areas, respectively. When grouped by category of neonatal death, the time trends of three categories showed statistically significant decreases: congenital malformations (APC = −9.97%), diseases of the perinatal period (APC = −6.04%), and diseases of the respiratory system (APC = −8.52%). Congenital malformations, diseases of the respiratory system, and diseases of the nervous system and sense organs were the three major contributors to the aforementioned decreasing trend, which accounted for 58.71% in overall areas. Among selective causes of neonatal death, the neonatal mortality rates of pneumonia, congenital heart disease, preterm birth and low birth weight, birth asphyxia, and intracranial hemorrhage of the newborn significantly decreased 7.87%, 7.32%, 2.47%, 11.04%, and 10.68% per year, respectively. In summary, neonatal mortality rates decreased in Shenyang during the 17-year study period. Future studies are warranted to further investigate the factors contributing to the neonatal mortality trends in China.

Although metastasis remains the overwhelming cause of death for patients with non-small cell lung cancer (NSCLC), the underlying mechanisms of metastasis remain unknown. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor cell invasion and metastasis. Expression of miR-9, miR-10b, miR-145, and miR-155, 4 miRNAs previously shown to play roles in metastasis in other tumor types, was compared in lymph node (LN)-positive NSCLC versus LN-negative NSCLC. Expression of miR-145 was significantly lower in LN-positive NSCLC (P < 0.05), while expression of miR-10b was significantly higher (P < 0.05). Expression of both miR-145 and miR-10b was correlated with lymph node metastasis in NSCLC (both Ps < 0.001). In addition, miR-10b facilitated the migration and invasion of lung cancer cell line A549, while miR-145 suppressed the migration and invasion capacity of A549 in vitro. These results suggest that miR-10b and miR-145 may act as an oncogene or tumor suppressor gene, respectively, in NSCLC metastasis.

Introduction Cardiovascular diseases are the leading cause of death in most countries. The aim was to examine the quality of life and to determine the differences in the quality of life in patients one year after myocardial infarction and the relationship between quality of life and echocardiographic parameters in these patients. Material and methods The research was a prospective, clinical, epidemiological study and was conducted at the Clinic of Cardiology, University Clinical Center Sarajevo (UCCS). The research was conducted on a sample of 160 patients who had acute myocardial infarction, which are based on the therapeutic procedures divided into four groups. The average age in the total sample was 54.9±8.8 years (range 37-76 years). The research was conducted one year after myocardial infarction (I group of subjects) or 12 months after PCI therapeutic procedures (II and III group of respondents) or coronary artery bypass surgery (IV group of respondents). Results Comparison of the mean scores of scales in SF-36 questionnaire showed that the highest total score had patients in the group II 67.3±15.2, and the lowest in the group I 57.8±21.4. The increase in ejection fraction leads to a statistically significant increase in quality of life scores at all subscales, in all groups, so that EF has the greatest impact on the quality of life in all respondents. Statistically significant differences in the effects of mitral regurgitation in particular groups have been recorded only in the case of the mental health scale. Conclusions Ejection fraction has the greatest impact on the quality of life in all patients, regardless of the type of medical treatment.

Amenable mortality (AM) is an indicator of medical care quality. This study aimed to assess the trend and magnitude of AM in Mongolia, with the purpose of providing evidence for decisions on resource allocation. This is the first study on AM trends in Mongolia. Retrospective analysis was done on mortality statistics for the period 2007–2014. Causes of death were coded according to the 10th revision of the International Classification of Diseases (ICD-10). Nolte & McKee’s classification of AM was used for the estimation of amenable mortality rates (AMRs) in Mongolia. During the study period, a total of 130,402 deaths were registered in Mongolia, of which 44,800 (34.4%) deaths were classified as being amenable. The age-standardized AMR per 100,000 population was highest in 2007 (226.6), and declined continuously until the level of 169.2 in 2014. The rate remained consistently higher in males than in females. Cerebrovascular diseases, ischemic heart diseases, perinatal deaths, influenza/pneumonia/asthma and tuberculosis were the leading causes of AM in the past eight years in Mongolia. The AMR was higher in remote western provinces with harsh weather conditions, high poverty rates, lack of human resources for health, and poor infrastructure. In addition, the provinces where Mongolia’s ethnic minorities live tended to have a higher AMR. The government of Mongolia needs to critically look at the regional differences in AM in order to allocate health resources, including human resources, effectively. Further studies are needed to look into the causes of regional disparities in AM, individual-level risk factors to amenable deaths, and validity of death coding in health sector.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n = 22), moderate (moTBI; n = 14) or mild TBI (mTBI; n = 108) according to Glasgow Coma Scale. The control group (n = 28) comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n = 23), moTBI (n = 7), mTBI (n = 37) patients and controls (n = 27). We show that two medium-chain fatty acids (decanoic and octanoic acids) and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC = 0.84 in validation cohort). Addition of the metabolites to the established clinical model (CRASH), comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified ‘TBI metabotype’ in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new avenue for the development of diagnostic and prognostic markers of broad spectrum of TBIs., Graphical Abstract Image 1, Highlights • The study reports that serum metabolites are sensitive to severity of TBI as well as predict the patient outcomes. • The findings are indicative of disruption in blood brain barrier and of protective response and altered TBI metabolism. • Metabolites significantly improved the prediction of patient outcomes when added to the established clinical model. Traumatic brain injury (TBI) is an example of a medical condition where there are still major lacks in diagnostics, outcome prediction, and the therapy development. Since the blood-brain barrier prevents diffusion of most water-soluble molecules with molecular mass over 500 Da, here we hypothesized that circulating small molecules (metabolites) are a potential source of TBI markers. Based on serum metabolomic studies in two independent cohorts, we found that metabolites are sensitive to severity of TBI as well as predict the patient outcomes. The findings of this study may pave the way for new diagnostic tools for TBI.

Purpose: The colorectal cancer (CRC) is the third leading cause of death in Korea. Ulcerative colitis (UC) is regarded as a risk factor of CRC. The aim of study is to confirm the incidence of CRC among subjects with and without a diagnosis of UC based on a sample of the Korean population. This study identified the effect of UC on incidence of CRC in Korea. Method: The data were from the population-based cohort containing National Health Insurance (NHI) claims from 2002 to 2013. We washed out first year (2002) for newly detected cases. Subjects who were under 20 years of age, diagnosed UC and CRC in 2002 development of CRC before diagnosis of UC since 2003, were excluded from analyses. Among 745,641 subjects during 11 years of follow-up (2003-2013), 7,448 patients with CRC were newly detected. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) of UC for CRC incidence. Confounding variables including gender, baseline age, type of social security, income level, residence, Charlson Comorbidity Index, hypertension and diabetes mellitus were incorporated into the model. Results: Overall annual incidence of UC and CRC were 6.7 and 95.4 per 100,000 during 11 years (2003~2013), respectively. Among 522 of newly detected UC cases, CRC incident cases were 12 cases during 11 years. The effects were stronger for male. Advancing age and Charlson Comorbidity Index, hypertension and diabetes mellitus increased the risk of CRC. This study showed that the adjusted hazard ratio of UC in incidence of CRC is 1.92 (95% confidence interval: 1.09-3.38). Also, male patients with UC have more HR than female patients with UC. Conclusion: The results of this study showed that patients with UC are the high risk group in incidence of CRC. Furthermore, the effects of UC in male patients are higher than those in female. The future study is needed to identify the effect of UC on mortality of CRC.

BACKGROUND: Hyperuricaemia, the biochemical precursor to gout, has been shown to be an independent risk factor for mortality from cardiovascular disease (CVD), although studies examining the clinical phenomenon of gout and risk of CVD mortality report conflicting results. This study aimed to produce a pooled estimate of risk of mortality from cardiovascular disease in patients with gout. DESIGN: Systematic review and meta-analysis. METHODS: Electronic bibliographic databases were searched from inception to November 2012, with results reviewed by two independent reviewers. Studies were included if they reported data on CVD mortality in adults with gout who were free of CVD at time of entry into the study. Pooled hazard ratios (HRs) for this association were calculated both unadjusted and adjusted for traditional vascular risk factors. RESULTS: Six papers, including 223,448 patients, were eligible for inclusion (all (CVD) mortality n = 4, coronary heart disease (CHD) mortality n = 3, and myocardial infarction mortality n = 3). Gout was associated with an excess risk of CVD mortality (unadjusted HR 1.51 (95% confidence interval, CI, 1.17-1.84)) and CHD mortality (unadjusted HR 1.59, 95% CI 1.25-1.94)). After adjusting for traditional vascular risk factors, the pooled HR for both CVD mortality (HR 1.29, 95% CI 1.14-1.44) and CHD mortality (HR 1.42, 95% CI 1.22-1.63) remained statistically significant, but none of the studies reported a significant association with myocardial infarction. CONCLUSIONS: Gout increases the risk of mortality from CVD and CHD, but not myocardial infarction, independently of vascular risk factors.

// Xiangrui Meng 1 , Peng Lu 2, * , Zhi Chu 3 , Qingxia Fan 1 1 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zheng Zhou, People's Republic of China 2 Department of Gastrointestinal Surgery, People's Hospital of Zhengzhou, Zheng Zhou, People's Republic of China 3 General Hospital, Jinan Military Command, Jinan, Shandong Province, People's Republic of China * Co-first author Correspondence to: Qingxia Fan, e-mail: fan_qingxia@126.com Keywords: ovarian cancer, AR, CAG, repeat, polymorphism Received: June 17, 2015 Accepted: October 08, 2015 Published: October 20, 2015 ABSTRACT Ovarian cancer is the main cause of death among women with gynecological malignancies. Androgen and its receptors play an important role in ovarian cancer pathogenesis. Here, We aim to evaluate the relationship between AR CAG and GGN repeat length polymorphisms and Epithelial Ovarian Cancer (EOC) risk in a two-stage, case-control study among Chinese women. The repeat length was analyzed as a categorical variable for CAG_A and GGN_A (average allele), CAG-S and GGN_S (shorter allele), CAG-L and GGN_L (longer allele), respectively. The median value of the repeat length among the controls was used as the cutoff point. Women with longer AR CAG repeats had a decreased risk of developing EOC. The results was replicated in an independent samples. Compared to those with shorter (

Aging is the most important risk factor in cardiovascular disease (CVD), which is the leading causes of death worldwide and the second major cause of death in Taiwan. The major factor in heart failure during aging is heart remodeling, including long-term stress-induced cardiac hypertrophy and fibrosis. Exercise is good for aging heart health, but the impact of exercise training on aging is not defined. This study used 3-, 12- and 18-month-old rats and randomly divided each age group into no exercise training control groups (C3, A12 and A18) and moderate gentle swimming exercise training groups (E3, AE12 and AE18). The protocol of exercise training was swimming five times weekly with gradual increases from the first week from 20 to 60 min for 12 weeks. Analyses of protein from rat heart tissues and sections revealed cardiac inflammation, hypertrophy and fibrosis pathway increases in aged rat groups (A12 and A18), which were improved in exercise training groups (AE12 and AE18). There were no heart injuries in young rat hearts in exercise group E3. These data suggest that moderate swimming exercise training attenuated aging-induced cardiac inflammation, hypertrophy and fibrosis injuries of rat hearts.

Background A large Midwestern state commissioned a virtual driving test (VDT) to assess driving skills preparedness before the on-road examination (ORE). Since July 2017, a pilot deployment of the VDT in state licensing centers (VDT pilot) has collected both VDT and ORE data from new license applicants with the aim of creating a scoring algorithm that could predict those who were underprepared. Objective Leveraging data collected from the VDT pilot, this study aimed to develop and conduct an initial evaluation of a novel machine learning (ML)–based classifier using limited domain knowledge and minimal feature engineering to reliably predict applicant pass/fail on the ORE. Such methods, if proven useful, could be applicable to the classification of other time series data collected within medical and other settings. Methods We analyzed an initial dataset that comprised 4308 drivers who completed both the VDT and the ORE, in which 1096 (25.4%) drivers went on to fail the ORE. We studied 2 different approaches to constructing feature sets to use as input to ML algorithms: the standard method of reducing the time series data to a set of manually defined variables that summarize driving behavior and a novel approach using time series clustering. We then fed these representations into different ML algorithms to compare their ability to predict a driver’s ORE outcome (pass/fail). Results The new method using time series clustering performed similarly compared with the standard method in terms of overall accuracy for predicting pass or fail outcome (76.1% vs 76.2%) and area under the curve (0.656 vs 0.682). However, the time series clustering slightly outperformed the standard method in differentially predicting failure on the ORE. The novel clustering method yielded a risk ratio for failure of 3.07 (95% CI 2.75-3.43), whereas the standard variables method yielded a risk ratio for failure of 2.68 (95% CI 2.41-2.99). In addition, the time series clustering method with logistic regression produced the lowest ratio of false alarms (those who were predicted to fail but went on to pass the ORE; 27.2%). Conclusions Our results provide initial evidence that the clustering method is useful for feature construction in classification tasks involving time series data when resources are limited to create multiple, domain-relevant variables.

Background Fatalities rarely occur in dental offices. Implications for clinicians may be deduced from scientific publications and internet reports about deaths in dental offices. Objective Data involving deaths in dental facilities were analyzed using Google as well as the PubMed database. By comparing both sources, we examined how internet data may enhance knowledge about deaths in dental offices obtained from scientific medical publications, which causes of death are published online, and how associated life-threatening emergencies may be prevented. Methods To retrieve relevant information, we searched Google for country-specific incidents of death in dental practices using the following keywords: “death at the dentist,” “death in dental practice,” and “dying at the dentist.” For PubMed searches, the following keywords were used: “dentistry and mortality,” “death and dental treatment,” “dentistry and fatal outcome,” and “death and dentistry.” Deaths associated with dental treatment in a dental facility, attributable causes of death, and documented ages of the deceased were included in our analysis. Deaths occurring in maxillofacial surgery or pre-existing diseases involved in the death (eg, cancer and abscesses) were excluded. A total of 128 cases from online publications and 71 cases from PubMed publications that met the inclusion criteria were analyzed using chi-square statistics after exclusion of duplicates. Results The comparison between the fatalities from internet (n=117) and PubMed (n=71) publications revealed that more casualties affecting minors appeared online than in PubMed literature (online 68/117, 58.1%; PubMed 20/71, 28%; P Conclusions Online and PubMed databases may increase awareness of life-threatening risks for patients during dental treatment. Negative aspects of anesthesia and sedation, as well as the number of deaths of young patients, were underestimated when reviewing PubMed literature only. Medical history of patients, medication dosages, and vital function monitoring are significant issues for practitioners. A high-impact finding from online reports was the underestimation of risks when performing sedation and even general anesthesia. Detailed knowledge of the definition and understanding of deep sedation and general anesthesia by dentists is of major concern. By avoiding potentially hazardous procedures, such as sedation-aided treatments performed solely by dentists, the risk of treatment-induced life-threatening emergencies may be reduced.

Cardiovascular disease remains the leading cause of death in the United States, and cardiopulmonary bypass is a cornerstone in the surgical management of many related disease states. Pathophysiologic changes associated both with extracorporeal circulation and shock can beget a syndrome of low systemic vascular resistance paired with relatively preserved cardiac output, termed vasoplegia. While increased vasopressor requirements accompany vasoplegia, related pathophysiologic mechanisms may also lead to true catecholamine resistance, which is associated with further heightened mortality. The introduction of a second non-catecholamine vasopressor, angiotensin II, and non-specific nitric oxide scavengers offers potential means by which to manage this challenging phenomenon. This narrative review addresses both the definition, risk factors, and pathophysiology of vasoplegia and potential therapeutic interventions.

Background In the United States, well-documented racial disparities in health outcomes are frequently attributed to racial bias and socioeconomic inequalities. However, it remains unknown whether racial disparities in mortality persist among those with higher socioeconomic status (SES) and occupational prestige. Objective As the celebrity population is generally characterized by high levels of SES and occupational prestige, this study aimed to examine survival differences between black and white film celebrities. Methods Using a Web-based, open-source encyclopedia (ie, Wikipedia), data for 5829 entries of randomly selected American film actors and actresses born between 1900 and 2000 were extracted. A Kaplan-Meier survival curve was conducted using 4356 entries to compare the difference in survival by race. A Cox semiparametric regression analysis examined whether adjusting for year of birth, gender, and cause of death influenced differences in survival by race. Results Most celebrities were non-Hispanic white (3847/4352, 88.4%), male (3565/4352, 81.9%), and born in the United States (4187/4352, 96.2%). Mean age at death for black celebrities (64.1; 95% CI 60.6-67.5 years) was 6.4 years shorter than that for white celebrities (70.5; 95% CI 69.6-71.4 years; P Conclusions There is some evidence that racial disparities in all-cause mortality may persist at higher levels of SES, but this association was no longer significant in adjusted analyses. Further research is needed to examine if racial disparities in mortality are diminished at higher levels of SES among more representative populations.

BACKGROUND: Cellulitis is a common cause of hospitalization. In the USA, the International Classification of Diseases (ICD) code “other cellulitis and abscess” accounts for 1.4% of all admissions and $5.5 billion in annual costs. The Infectious Disease Society of America recommends hospitalization for patients with cellulitis under certain circumstances but there is little actual clinical evidence to guide the decision to admit. The purpose of this study is to determine the mortality rate of patients hospitalized with cellulitis and to ascertain if the rate is comparable to the rate for low risk patients with community acquired pneumonia that are currently recommended for outpatient management. METHODS: A systematic literature search was conducted for studies of consecutive patients hospitalized with cellulitis or erysipelas that reported inpatient mortality. Study quality was assessed using a modified Newcastle-Ottawa Quality Assessment Scale. The mortality rates from the included studies were pooled using a random effects model. Heterogeneity was estimated using the I(2) statistic. RESULTS: Eighteen studies met inclusion criteria. The overall worldwide mortality rate was 1.1% (95% confidence interval (CI), 0.7–1.8). For studies from the USA, the rate was 0.5% (95% CI 0.3–0.9). The actual cause of death was generally poorly described, and only one third of deaths appeared to be due to infection. DISCUSSION: The estimated mortality rate for patients currently being hospitalized for cellulitis is comparable to the mortality rate of patients with community-acquired pneumonia that are recommended for outpatient management by the Pneumonia Severity Index and CURB65 prediction models and strongly endorsed by major infectious disease societies. Outpatient management of these patients could result in large cost savings and may be much preferred by patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-018-4546-z) contains supplementary material, which is available to authorized users.

Background: Herpes zoster (HZ), or shingles, is caused by reactivation of varicella-zoster virus in latently infected individuals. Live-attenuated HZ vaccine (zoster vaccine live, ZVL) is approved in the United States for persons aged ≥50 years and recommended by the CDC for persons ≥60 years. Methods: We analyzed U.S. reports of adverse events (AEs) following ZVL submitted to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system to monitor vaccine safety, for persons vaccinated May 1, 2006, through January 31, 2015. We conducted descriptive analysis, clinical reviews of reports with selected pre-specified conditions, and empirical Bayesian data mining. Results: VAERS received 23,092 reports following ZVL, of which 22,120 (96%) were classified as non-serious. Of reports where age was documented (n = 18,817), 83% were in persons aged ≥60 years. Reporting rates of AEs were 106 and 4.4 per 100,000 ZVL doses distributed for all reports and serious reports, respectively. When ZVL was administered alone among persons aged ≥50 years, injection site erythema (27%), HZ (17%), injection site swelling (17%), and rash (14%) were the most commonly reported symptoms among non-serious reports; HZ (29%), pain (18%), and rash (16%) were the most commonly reported symptoms among serious reports. Six reports included laboratory evidence of vaccine-strain varicella-zoster virus (Oka/Merck strain) infection; AEs included HZ, HZ- or varicella-like illness, and local reaction with vesicles. In our review of reports of death with sufficient information to determine cause (n = 46, median age 75 years), the most common causes were heart disease (n = 28), sepsis (n = 4), and stroke (n = 3). Empirical Bayesian data mining did not detect new or unexpected safety signals. Conclusions: Findings from our safety review of ZVL are consistent with those from pre-licensure clinical trials and other post-licensure assessments. Transient injection-site reactions, HZ, and rashes were most frequently reported to VAERS following ZVL. Overall, our results are reassuring regarding the safety of ZVL.

Aims Systematic reviews report an association between poorer oral health and an increased risk of coronary heart disease. This contentious relationship may not be causal but existing studies have been insufficiently well powered comprehensively to examine the role of confounding, particularly by cigarette smoking. Accordingly, we sought to examine the role of smoking in generating the relationship between oral health and coronary heart disease in life-long non-smokers. Methods and results In the Korean Cancer Prevention Study, 975,685 individuals (349,579 women) aged 30–95 years had an oral examination when tooth loss, a widely used indicator of oral health, was ascertained. Linkage to national mortality and hospital registers over 21 years of follow-up gave rise to 64,784 coronary heart disease events (19,502 in women). In the whole cohort, after statistical adjustment for age, there was a moderate, positive association between tooth loss and coronary heart disease in both men (hazard ratio for seven or more missing teeth vs. none; 95% confidence interval 1.08; 1.02, 1.14; Ptrend across tooth loss groups

Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide and late diagnosis is the main cause of death in HCC patients. In this study expression patterns of HSP70, GPC3 and GS and their relationships with pathogenesis of HCC in Iranian patients were investigated. The expression of HSP70, GPC3 and GS were determined by immunohistochemistry and quantitative real-time PCR (q-PCR) methods, using 121 cases from patients with HBV alone, HCC without HBV, HBV+HCC and 30 normal tissues as control group. HSP70, GPC3 and GS were expressed in higher levels in HBV-related HCC samples compared to HBV alone group. The results showed that the labeling index of HSP70, GPC3 and GS are correlated with immunohistochemical and molecular expressions of HSP70, GPC3 and GS. The sensitivity and specificity for HCC diagnosis were 43.4% and 89.7% for HSP70, 64.3% and 90.4% for GPC3, and 60.7% and 94.3% for GS, respectively. The sensitivity and specificity of the panels with 3, 2 and 1 positive markers, regardless of which one, were 21.6% and 100%, 51.3% and 100% and 93.4% and 80.5% respectively. The current study demonstrated an association between HSP70, GPC3 and GS expressions and HBV-related HCC in our population. It was concluded that HSP70, GPC3 and GS expressions could be useful biomarkers for increasing the specificity and sensitivity of HCC diagnosis to acceptable level. Also, proper combinations of these 3 markers could improve diagnostic accuracy.

OBJECTIVE: The purpose was to evaluate the presence of gas in the tissue adjacent to the laryngeal structures, "the gas bubble sign", in cases of hanging as a diagnostic indicator of neck trauma. METHODS: In this study, post-mortem CT (PMCT) scans and autopsies of 35 victims of hanging were examined to reveal age-dependent changes, laryngeal fracture, fracture location and the presence of gas. A matched group with cardiac arrest or intoxication was used as controls (n = 35). An autopsy was performed in each case. RESULTS: Incomplete suspension was the most common method in hanging. The thyroid horns (90.5%) were identified as the most vulnerable location for fractures. Laryngeal deformity and dislocation, which was only detected on PMCT, was observed in 57.1% and was concomitant with fractures in 83.3%. Laryngeal fractures are more common with advanced age (>40 years, 88.9%) and less common in younger subjects (

Purpose: To stratify upper urinary tract urothelial carcinoma (UTUC) patients into risk groups in terms of 5-year survival. Methods and materials: All potential UTUC patients recorded in our cancer registry database from 1997 to 2011 were evaluated for authentic presence of UTUC. Age at diagnosis, sex, organ involvement, dialysis, renal transplantation status, clinical stage, survival to the last follow-up, and the cause of death of each patient were recorded. All patients were randomized into a developmental set or a validation set at a 1:1 ratio. Survival prediction models and scores were developed using the developmental set and validated in terms of discrimination and calibration using the validation set. Patients were stratified into risk groups using the summed risk scores and their survival compared by the log rank test. Results: We enrolled 1,120 authentic UTUC patients. In the developmental set, older age, male sex, and higher clinical staging were significant predictors of 5-year death after controlling for other variables. Based on these three clinical variables, patients were stratified into low-, intermediate-, high-, and very high-risk groups using the summed risk scores. The 5-year all-cause and cancer-specific survivals of UTUC patients in the low-, intermediate-, high-, and very high-risk groups were 83.0% and 85.0%, 57.7% and 70.9%, 16.8% and 26.3%, and 2.2% and 7.5%, respectively (p < 0.001). Both discrimination and calibration were good for the validation set (overall concordance index = 0.762). Conclusions: Stratification of UTUC patients using summed risk scores was a simple and useful way to estimate survivals and to select appropriate treatments.

Background: measuring the quality of primary palliative care for older people with dementia in different countries is important to identify areas where improvements can be made. Objective: using quality indicators (QIs), we systematically investigated the overall quality of primary palliative care for older people with dementia in three different countries. Design/setting: a mortality follow-back survey through nation-and region-wide representative Sentinel Networks of General Practitioners (GPs) in Belgium, Italy and Spain. GPs registered all patient deaths in their practice. We applied a set of nine QIs developed through literature review and expert consensus. Subjects: patients aged 65 or older, who died non-suddenly with mild or severe dementia as judged by GPs (n = 874). Results: findings showed significantly different QI scores between Belgium and Italy for regular pain measurement (mild dementia: BE = 44%, IT = 12%, SP = 50% | severe dementia: BE = 41%, IT = 9%, SP = 47%), acceptance of approaching death (mild: BE = 59%, IT = 48%, SP = 33% | severe: BE = 41%, IT = 21%, SP = 20%), patient-GP communication about illness (mild: BE = 42%, IT = 6%, SP = 20%) and involvement of specialised palliative services (mild: BE = 60%, IT = 20%, SP = 77%). The scores in Belgium differed from Italy and Spain for patient-GP communication about medical treatments (mild: BE = 34%, IT = 12%, SP = 4%) and repeated multidisciplinary consultations (mild: BE = 39%, IT = 5%, SP = 8% | severe: BE = 36%, IT = 10%, SP = 8%). The scores for relative-GP communication, patient death outside hospitals and bereavement counselling did not differ between countries. Conclusion: while the countries studied differed considerably in the overall quality of primary palliative care, they have similarities in room for improvement, in particular, pain measurement and prevention of avoidable hospitalisations.

Traumatic brain injury (TBI) is the leading cause of death after traumatic injury. Raised intracranial pressure (ICP) is particularly associated with poor TBI outcomes, prompting clinicians to monitor this parameter, using it to guide therapies aimed at reducing pressures. Despite this approach being recommended by several bodies such as the Brain Trauma Foundation and the American College of Surgeons, the evidence demonstrating that ICP-guided therapy improves outcome is limited. The topic was debated at the 36th Annual Point/Counterpoint Acute Care Surgery Conference and the following article summarizes the discussants points of view along with a summary of the evidence. Level of evidence Level III.

Colorectal cancer (CRC) is a leading cause of death worldwide. Surgical intervention is a successful treatment for stage I patients, whereas other more advanced cases may require adjuvant chemotherapy. The selection of effective adjuvant treatments remains, however, challenging. Accurate patient stratification is necessary for the identification of the subset of patients likely responding to treatment, while sparing others from pernicious treatment. Targeted sequencing approaches may help in this regard, enabling rapid genetic investigation, and at the same time easily applicable in routine diagnosis.We propose a set of guidelines for the identification, including variant calling and filtering, of somatic mutations driving tumorigenesis in the absence of matched healthy tissue. We also discuss the inclusion criteria for the generation of our gene panel. Furthermore, we evaluate the prognostic impact of individual genes, using Cox regression models in the context of overall survival and disease-free survival. These analyses confirmed the role of commonly used biomarkers, and shed light on controversial genes such as CYP2C8.Applying those guidelines, we created a novel gene panel to investigate the onset and progression of CRC in 273 patients. Our comprehensive biomarker set includes 266 genes that may play a role in the progression through the different stages of the disease. Tracing the developmental state of the tumour, and its resistances, is instrumental in patient stratification and reliable decision making in precision clinical practice.

// David Perez-Callejo 1, * , Lorea Zurutuza 1, * , Ana Royuela 2 , Maria Torrente 1 , Beatriz Nunez 1 , Virginia Calvo 1 , Miriam Mendez 1 , Fernando Franco 1 , Maria Auxiliadora Brenes 1 , Juan Cristobal Sanchez 1 and Mariano Provencio 1 1 Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain 2 Statistics Department, Hospital Universitario Puerta de Hierro–Majadahonda, Madrid, Spain * These authors contributed equally to this work Correspondence to: Mariano Provencio, email: mariano.provencio@salud.madrid.org Keywords: Hodgkin lymphoma; survival; standardized mortality ratio Received: September 27, 2017 Accepted: January 13, 2018 Published: February 03, 2018 ABSTRACT Background: Hodgkin lymphoma (HL) is the paradigm of curable disease. This study analyzed the overall survival (OS) of patients with HL and compared their survival between decades and with the expected survival of a general population. Results: The median follow-up was 22 years. The median OS was 33 years. The incidence mortality rate for all causes is 2 per every 100 patients per year. The OS of our cohort at 10 years from diagnosis was 76% (95% CI: 72–79) and 52% at 30 years (95% CI: 48–57). Overall SMR (1980–2013) was 2,943 (95% CI: 2,518–3,439). Excluding the primary tumor as the cause of death, the SMR obtained is 2,266 (95% CI: 1,895–2,710). The SMR for those patients diagnosed before the year 2000 was 2,097 (95% CI: 1,732–2,539); and for those diagnosed after 2000 was 5,218 (95% CI: 8,655). The group of patients diagnosed after 2000 had statistically significant more advanced stages, were older and less responsive to treatment. Conclusions: Despite the advances achieved, the risk of death remains higher than in the general population, mainly for those patients diagnosed after year 2000, even after almost 40 years of follow-up. This data might suggest a shift to more aggressive forms of disease in recent years. Patients and methods: A total of 595 patients diagnosed with HL were included between January 1966 and February 2014. The standardized mortality ratio (SMR) was analyzed using the annual rate of mortality in the general Spanish population, adjusted for age, sex and time period.

Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI; 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI; BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated., This work was funded by the Wellcome Trust. SB is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (100087/Z/12/Z). NTH is currently funded by a Mervyn Susser Fellowship at Columbia University Medical Center, USA

Objectives We aimed to prospectively examine the associations of total, domain-specific, and intensity-specific physical activity with all-cause and cardiovascular mortality among Chinese hypertensive adults. Methods We performed a prospective cohort study in 150 391 hypertensive participants aged 30–79 years from the China Kadoorie Biobank study of 512 891 participants recruited from 10 diverse areas across China during 2004– 2008. Participants with heart disease, stroke, chronic obstructive pulmonary disease, and cancer at baseline were excluded. Results During 1069 863 person-years of follow-up (median 7.1 years), a total of 5332 men and 4384 women died. Compared with hypertensive participants in the lowest level of total physical activity, the hazard ratios for all-cause mortality were 0.80 (0.76–0.84), 0.69 (0.65–0.73), and 0.67 (0.62–0.72) for those in quartiles 2–4 (Ptrend Conclusion Among Chinese hypertensive adults, a higher level of physical activity reduces all-cause and cardiovascular mortality, independent of intensities of physical activity. Not only leisure-time but also occupational and domestic physical activities were benefited.

BackgroundSuicide is a leading cause of death for young people. Children living in sub-Saharan Africa, where HIV rates are disproportionately high, may be at increased risk.AimsTo identify predictors, including HIV status, of suicidal ideation and behaviour in Rwandan children aged 10–17.MethodMatched case–control study of 683 HIV-positive, HIV-affected (seronegative children with an HIV-positive caregiver), and unaffected children and their caregivers.ResultsOver 20% of HIV-positive and affected children engaged in suicidal behaviour in the previous 6 months, compared with 13% of unaffected children. Children were at increased risk if they met criteria for depression, were at high-risk for conduct disorder, reported poor parenting or had caregivers with mental health problems.ConclusionsPolicies and programmes that address mental health concerns and support positive parenting may prevent suicidal ideation and behaviour in children at increased risk related to HIV.

A cross-sectional survey was conducted in neonatal and maternity units of five Kenyan district public hospitals. Data for 1 year were obtained: 3999 maternal and 1836 neonatal records plus tallies of maternal deaths, deliveries and stillbirths. There were 40 maternal deaths [maternal mortality ratio: 276 per 100 000 live births, 95% confidence interval (CI): 197–376]. Fresh stillbirths ranged from 11 to 43 per 1000 births. A fifth (19%, 263 of 1384, 95% CI: 11–30%) of the admitted neonates died. Compared with normal birth weight, odds of death were significantly higher in all of the low birth weight (LBW

Objective To examine the impact of plain packaging of cigarettes with enhanced graphic health warnings on Australian adolescents’ cognitive processing of warnings and awareness of different health consequences of smoking. Methods Cross-sectional school-based surveys conducted in 2011 (prior to introduction of standardised packaging, n=6338) and 2013 (7–12 months afterwards, n=5915). Students indicated frequency of attending to, reading, thinking or talking about warnings. Students viewed a list of diseases or health effects and were asked to indicate whether each was caused by smoking. Two—‘kidney and bladder cancer’ and ‘damages gums and teeth’—were new while the remainder had been promoted through previous health warnings and/or television campaigns. The 60% of students seeing a cigarette pack in previous 6 months in 2011 and 65% in 2013 form the sample for analysis. Changes in responses over time are examined. Results Awareness that smoking causes bladder cancer increased between 2011 and 2013 (p=0.002). There was high agreement with statements reflecting health effects featured in previous warnings or advertisements with little change over time. Exceptions to this were increases in the proportion agreeing that smoking was a leading cause of death (p

Introduction Colorectal cancer is the second leading cause of death due to cancer in Poland. The traditional approach to treat patients included a surgical procedure. Irrespective of the surgical method being used, surgical treatment of malignant colorectal obstruction is associated with prolonged hospitalisation, and the postoperative mortality rate is approximately 5–11%. Due to these problems, more interest has been shown in less invasive methods. Prosthesis implantation is a leading endoscopic method used currently in palliative or preoperative treatment. Aim To compare the results of implantation of traditional stents with the results of implantation of an own stent using minimally invasive methods. Material and methods Left-sided colon obstruction due to cancer was an indication for transplantation. All patients were aged over 70 years and had serious concomitant diseases. The control group included 50 patients with colorectal cancer who received traditional stents in the period 2009–2011. Our stent covers only the internal length of a tumour. It is not equipped with anti-migration flares. To minimize the risk of migration it has a system of hooks that are responsible for permanent anchorage of the stent within the tumour mass. Results Implantation technical and clinical success defined as effective decompression of intestinal obstruction was 100% in both groups. There were 2 cases of stent migration in the control group. Conclusions It is possible to achieve a secure surgical anastomosis after intestinal decompression. Stent implantation is fast and safe thanks to the positioning system that was used. The use of labelled hooks is a secure anti-migration solution.

Objectives: The aim of this study was to evaluate the association of the levels of red blood cell distribution width (RDW) with the severity of atherosclerosis and to determine whether or not the RDW level on admission is an independent predictor of all-cause mortality in patients with non-ST elevation myocardial infarction (NSTEMI). Materials and Methods: A total of 335 consecutive patients with NSTEMI were enrolled in this study. The patients were divided into high (n = 105) and low (n = 230) SYNTAX groups. The high SYNTAX group was defined as patients with a value in the third tertile (SYNTAX score, SXscore ≥12), while the low SYNTAX group was defined as those with a value in the lower 2 tertiles (SXscore 14.25% and the low RDW group (n = 183) as those with RDW ≤14.25%. All-cause mortality was followed up to 38 months. Results: The mean follow-up period was 18 ± 11 months. The RDW levels of patients were significantly higher in the high SYNTAX group than in the low SYNTAX group (15.2 ± 1.8 vs. 14.2 ± 1.2, p < 0.001). Pearson's coefficients were used to determine the degree of association between RDW levels and SXscore and also between RDW levels and high-sensitivity C-reactive protein. There was a significant correlation between RDW levels and SXscore (r = 0.460, p < 0.001). Also, there was a significant correlation between RDW levels and high-sensitivity C-reactive protein (r = 0.180, p = 0.001). All-cause mortality rate was not significantly different between the high and low RDW groups (log-rank, p = 0.621). Conclusion: RDW levels were independently associated with high SXscore but were not associated with long-term mortality in NSTEMI patients.

ObjectiveThe present study investigates the relationship between BMI and all-cause mortality among middle-aged and older adults with or without pre-existing diseases.DesignA population-based cohort study.SettingThe Taiwan Longitudinal Study on Aging is a nationwide prospective cohort study comprising a representative random sample of middle-aged and older adults. The study period was 1996–2007.SubjectsWe followed 4145 middle-aged and older adults, totalling 42 353 person-years.ResultsOverweight and mildly obese participants showed a 16 % and 30 % decrease in the risk of death, respectively, compared with those of normal weight after adjusting for potential covariates (e.g. demographic characteristics, health behaviour, co-morbidities and physical function). Underweight adults showed a 1·36-fold increased adjusted hazard ratio of death compared with normal-weight adults. Adults with a BMI of 27·0–28·0 kg/m2 showed a significantly lower adjusted hazard ratio of all-cause mortality rate compared with adults who had normal BMI values when they had coexisting hypertension or diabetes (adjusted hazard ratio=0·50; 95 % CI 0·30, 0·81 for hypertension and adjusted hazard ratio=0·41; 95 % CI 0·18, 0·89 for diabetes).ConclusionsThe study demonstrates that underweight people have a higher risk of death, and overweight and mildly obese people have a lower risk of death, compared with people of normal weight among middle-aged and older adults. An optimal BMI may be based on the individual, who exhibits pre-existing diseases or not.

This study investigated lung cancer and other diseases related to insoluble beryllium compounds. A cohort of 4950 workers from four US insoluble beryllium manufacturing facilities were followed through 2009. Expected deaths were calculated using local and national rates. On the basis of local rates, all-cause mortality was significantly reduced. Mortality from lung cancer (standardized mortality ratio 96.0; 95% confidence interval 80.0, 114.3) and from nonmalignant respiratory diseases was also reduced. There were no significant trends for either cause of death according to duration of employment or time since first employment. Uterine cancer among women was the only cause of death with a significantly increased standardized mortality ratio. Five of the seven women worked in office jobs. This study confirmed the lack of an increase in mortality from lung cancer and nonmalignant respiratory diseases related to insoluble beryllium compounds. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

One hundred and twenty stranding events of Stejneger's beaked whales were reported in Japan between 1999 and 2011. The purpose of this study is to introduce pathological data and to discuss probable causes of death for 44 Stejneger's beaked whales among them. The significant pathological findings were the pulmonary edema, parasitic granulomatous nephritis, emaciation, amyloidosis, suppurative bronchopneumonia and so on. The probable causes of death were categorized as noninfectious in 43 of the cases, which included drowning, starvation and secondary amyloidosis. One individual was diagnosed with septicemia, which was the only example of an infectious disease. Because we could not always perform advanced analyses, such as microbiology tests, biotoxin examinations or contaminant analyses, the finality of our findings may be impaired. However, the present study has broad implications on the causes of death of Stejneger's beaked whales of the seas around Japan, which are valuable for the future studies and for the detection of emerging diseases.

Cancer is the second leading cause of death, and the most common diagnosis among the general population is breast and colon cancer. Recently, an increasing number of new cases of invasive breast and colon cancer have been estimated, and more people die from these diseases. In addition to the genetic pattern, diet and lifestyle including smoking, alcohol consumption, and sedentary behaviour have also been identified as potential risks factors. Recent studies of cancer survivors have shown the beneficial effects of regular physical activity to reduce the prevalence of comorbidity, muscle atrophy, weight changes, reduced aerobic capacity, fatigue, depression, and reduced quality of life. Dedicated and individual programs are crucial for achieving the goals of improving quality of life and reducing comorbidities. A multidisciplinary approach is fundamental: lifestyle assessment, including estimating the level of physical activity, as well as nutritional habits, may be the first step. A periodic cardiovascular examination is crucial for detecting asymptomatic early myocardial failure. According to current ACSM guidelines, different levels of exercise (low-moderate 40% and moderate up to 60% of the maximal HR) may be prescribed, and patients enrolled may follow the exercise program if in the absence of contraindications. The current paper reports observations from our clinical practice and provides practical strategies that bridge contemporary, published guidelines into practice within a multi-disciplinary team working with cancer survivors in Italy.

This paper highlights the relevance of age-specific hazard rates in explaining the age variation in "value of statistical life" (VSL) figures. The analysis-which refers to a stated preference framework-contributes to the ongoing discussion of whether benefits resulting from reduced mortality risk should be valued differently depending on the age of the beneficiaries. By focussing on a life-threatening environmental phenomenon I show that the consideration of the individual's age-specific hazard rate is important. If a particular risk affects all individuals regardless of their age so that their hazard rate is age-independent, VSL is rather constant for people at different age; if hazard rate varies with age, VSL estimates are sensitive to age. The results provide an explanation for the mixed outcomes in empirical studies and illustrate in which cases an adjustment to age may or may not be justified. Efficient provision of live-saving measures requires that such differences to be taken into account.

// Min-Huey Chung 1 , Yi-Wen Wang 2 , Yung-Lung Chang 3 , Shih-Ming Huang 3 and Wei-Shiang Lin 4 1 Graduate Institute of Nursing, College of Nursing, Taipei Medical University, Taipei 110, Taiwan, Republic of China 2 Department of Biology and Anatomy, National Defense Medical Center, Taipei City 114, Taiwan, Republic of China 3 Department of Biochemistry, National Defense Medical Center, Taipei City 114, Taiwan, Republic of China 4 Department of Medicine, Division of Cardiology, Tri-Service General Hospital, National Defense Medical Center, Taipei City 114, Taiwan, Republic of China Correspondence to: Wei-Shiang Lin, email: wslin545@ms27.hinet.net Keywords: heart failure, digoxin, cancer, cell-based strategy, personalized medicine Received: February 18, 2017 Accepted: March 30, 2017 Published: April 25, 2017 ABSTRACT Heart failure (HF) is the leading cause of death in the world and digoxin remains one of the oldest therapies for HF. However, its safety and efficacy have been controversial since its initial use and there is uncertainty about its long-term efficacy and safety. Recently, the repositioning of cardiac glycosides is to function in anti-tumor activity via multiple working pathways. It is interesting to compare the potential effects of digoxin in clinical patients and cell lines. First, we analyze patient information retrieved from the National Health Insurance Research database of Taiwan between January 1, 2000 and December 31, 2000. This retrospective study included a study cohort (1,219 patients) and a comparison cohort. Our analytical data suggested that patients taking digoxin are at an increased risk of cancers, including breast, liver, and lung cancers, during the 10-year follow-up period. In contrast to the anti-tumor function of digoxin, we further examined the potential pathway of digoxin via the cell-based strategy using several breast cancer cell lines, including MCF-7, BT-474, MAD-MB-231, and ZR-75-1. Digoxin consistently exerted its cytotoxicity to these four cell lines with various range of concentration. However, the proliferation of ZR-75-1 cells was the only cell lines induced by digoxin and the others were dramatically suppressed by digoxin. The responsiveness of SRSF3 to digoxin might be involved with cell-type differences. In summary, we combined a cohort study for digoxin treatment for HF patients with a cell-based strategy that addresses the translation issue, which revealed the complexity of personalized medicine.

Öztürk, Savaş (Balikesir Author), Introduction: Renal involvement in leprosy has previously been described in the literature and can include amyloidosis, glomerulonephritis, nephrosclerosis, tubulointerstitial nephritis, and granulomas. Aim: To evaluate renal involvement in Turkish patients with leprosy. Material and methods: In total, 32 patients with lepromatous leprosy but without any co-morbidities and 35 healthy control subjects were evaluated for renal involvement at the Elazig Training and Research Hospital in Turkey. The laboratory tests and radiological results concerning renal function were taken from both the patients' medical records and from current examinations. Results: The levels of creatinine, urea, and leukocyturia in the lepromatous leprosy patients were significantly higher than in the controls (p < 0.001, p < 0.001; p = 0.001, p < 0.01; p = 0.036, p < 0.05, respectively). No significant differences in the proteinuria, hematuria, sodium, or potassium levels were found between the leprosy and control groups (p > 0.05). On ultrasonographic examination, the prevalence of renal cortical cysts and renal cortical echogenicity in the leprosy patients was significantly higher than in the controls (p = 0.020, p < 0.05, respectively). There were no significant differences in terms of nephrolithiasis, parapelvic cysts, or hydronephrosis between the leprosy and control groups (p > 0.05). Conclusions: Evaluating the renal:function in all leprosy patients is important to detect abnormalities and to prevent renal failure, which remains a potential cause of death in this disease.

Background: Little information is available about care before death among human immunodeficiency virus (HIV)–infected persons who die of HIV infection, compared with those who die of other causes. Objective: The objective of our study was to compare HIV care and outcome before death among persons with HIV who died of HIV-attributable versus other causes. Methods: We used National HIV Surveillance System data on CD4 T-lymphocyte counts and viral loads within 12 months before death in 2012, as well as on underlying cause of death. Deaths were classified as “HIV-attributable” if the reported underlying cause was HIV infection, an AIDS-defining disease, or immunodeficiency and as attributable to “other causes” if the cause was anything else. Persons were classified as “in continuous care” if they had ≥2 CD4 or viral load test results ≥3 months apart in those 12 months and as having “viral suppression” if their last viral load was

Natriuretic peptides (NPs) are a family of prognostic biomarkers in patients with heart failure (HF). HF is one of the most frequent comorbidities in patients with chronic obstructive pulmonary disease (COPD). However, the prognostic role of NP in COPD patients remains unclear. The aim of this meta-analysis was to evaluate the relation between NP and all-cause mortality in COPD patients. We performed a systematic review and meta-analysis of observational studies assessing prognostic implications of elevated NP levels on all-cause mortality in COPD patients. Nine studies were considered for qualitative analysis for a total of 2788 patients. Only two studies focused on Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and brain natriuretic peptide (BNP), respectively, but seven studies focused on pro-BNP (NT-proBNP) and were included in the quantitative analysis. Elevated NT-proBNP values were related to increased risk of all-cause mortality in COPD patients both with and without exacerbation (hazard ratio (HR): 2.87, p < 0.0001 and HR: 3.34, p = 0.04, respectively). The results were confirmed also after meta-regression analysis for confounding factors (previous cardiovascular history, hypertension, HF, forced expiratory volume at 1 second and mean age). NT-proBNP may be considered a reliable predictive biomarker of poor prognosis in patients with COPD.

Introduction Survival after radical cystectomy (RC) is affected by various factors. Significance of preoperative health status and its influence on treatment outcome is uncertain. The aim of the study was to prospectively evaluate overall survival, cause of death and the role of comorbidities in mortality during the first 12 months following RC. Material and methods All patients who underwent RC between January 2014 and May 2016 for T1-T4 bladder cancer in a single center were prospectively followed. Stage and comorbidities were explored as predictors of overall survival (OS). Patient status was assessed for at least 12 months. Results Follow-up was available for 25 men and 19 women at the mean age 67. Median time of follow-up for survivors was 16 months. Six-month and 1-year OS was 84% and 77%. Out of 11 deaths, 8 were related to cancer progression and 3 patients died for other causes. All deaths apart from one occurred in the first year after surgery. One-year OS was affected mostly by tumor stage: 95% for pT1-2 vs. 62.5% for pT3-4; p = 0.01. Worse outcome was found in patients ≥72 years old, (44% vs. 86%; p = 0.02) and among women (63% vs. 88%; p = 0.07). When patients who died were compared to survivors the following distribution of comorbidities was found: diabetes mellitus - 30.0% vs. 11.8%, p = 0.3; history of stroke - 30.0% vs. 2.9%, p = 0.1; thyroid disease - 30.0% vs. 11.8%, p = 0.3. Conclusions Majority of patients died because cystectomy was performed too late. History of stroke, diabetes mellitus, and thyroid diseases should be assessed as possible risk factors in larger studies.

Background Current evidence concerning sedentary behaviour and mortality risk has used single time point assessments of sitting. Little is known about how changes in sitting levels over time affect subsequent mortality risk. Aim To examine the associations between patterns of sitting time assessed at two time points 11 years apart and risk of all-cause and cardio-metabolic disease mortality. Methods Participants were 25,651 adults aged > =20 years old from the Nord-Trøndelag Health Study with self-reported total sitting time in 1995-1997 (HUNT2) and 2006-2008 (HUNT3). Four categories characterised patterns of sitting: (1) low at HUNT2/ low at HUNT3, ‘consistently low sitting’; (2) low at HUNT2/high at HUNT3, ‘increased sitting’; (3) high at HUNT2/low at HUNT3, ‘reduced sitting’; and (4) high at HUNT2 /high at HUNT3, ‘consistently high sitting’. Associations of sitting pattern with all-cause and cardio-metabolic disease mortality were analysed using Cox regression adjusted for confounders. Results Mean follow-up was 6.2 years (158880 person-years); 1212 participants died. Compared to ‘consistently low sitting’, adjusted hazard ratios for all-cause mortality were 1.51 (95% CI: 1.28–2.78), 1.03 (95% CI: 0.88–1.20), and 1.26 (95% CI: 1.06–1.51) for ‘increased sitting’, ‘reduced sitting’ and ‘consistently high sitting’ respectively. Conclusions Examining patterns of sitting over time augments single time-point analyses of risk exposures associated with high sitting time. Whilst sitting habits can be stable over a long period, life events (e.g., changing jobs, retiring or illness) may influence sitting trajectories and therefore sitting-attributable risk. Reducing sitting may yield mortality risks comparable to a stable low-sitting pattern. © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Over the last few years the role of doctors around the time of death has been subjected to intense scrutiny, particularly during the inquiries into the Shipman murders and the retention of post mortem specimens at Alder Hey Hospital.1,2 These inquiries led to Fundamental Reviews of Death Certification and The Role of the Coroners Services (the Luce Report)3 and the drafting of The Coroners and Justice Bill4 which completed its transit through the House of Lords in October 2009. Although the law is not expected to change until 2012, guidance regarding confirmation of death and cremation forms has been updated and there has been a shift in routine practises, such as viewing the body after death and involving the relatives more in the exchange of information. It is likely in the future, when systems have been developed, that doctors will certify deaths online – as the final entry in the electronic patient record. A patient death, even when expected, can cause considerable distress. Doctors play a key role in a number of important (and urgent) practical processes. It is expected that doctors report relevant cases to the coroner, but badly written death certificates may also result in a case being referred directly by the Registrar of Births, Deaths and Marriages resulting in unnecessary delays and possibly an unwelcome postmortem. This chain of events is upsetting and may give rise to complaints. This paper is written with GPs and their registrars in mind. Some of the information applies only to England and Wales, but the tips on completing the cause of death statement can be applied universally.

SUMMARYDeath certificate reports and laboratory-confirmed influenza deaths probably underestimate paediatric deaths attributable to influenza. Using US mortality data for persons aged

// Saverio Candido 1,2 , Roberta Maestro 3 , Jerry Polesel 2 , Alessia Catania 1 , Francesca Maira 1 , Santo S. Signorelli 4 , James A. McCubrey 5 and Massimo Libra 1 1 Department of Bio-medical Sciences, Section of Pathology & Oncology, Laboratory of Translational Oncology & Functional Genomics, University of Catania, Catania, (Italy); 2 Epidemiology and Statistic Unit, CRO National Cancer Institute, Aviano, (Italy); 3 Unit of Experimental Oncology 1, CRO National Cancer Institute, Aviano, (Italy); 4 Department of Medical and Pediatric Sciences, Medical Angiology Unit; University of Catania, Catania (Italy); 5 Brody School of Medicine at East Carolina University, Department of Microbiology & Immunology, Greenville, NC, (USA); Correspondence: Massimo Libra, email: // Key words : NGAL, LCN2, Lipocalin 2, mRNA expression, cancer, biomarker, prognostic factor, metastasis, protein expression Received : December 23, 2013 Accepted : January 30, 2014 Published : February 1, 2014 Abstract Cancer remains one of the major cause of death in the Western world. Although, it has been demonstrated that new therapies can improve the outcome of cancer patients, still many patients relapse after treatment. Therefore, there is a need to identify novel factors involved in cancer development and/or progression. Recently, neutrophil gelatinase-associated lipocalin (NGAL) has been suggested as a key player in different cancer types. Its oncogenic effect may be related to the complex NGAL/MMP-9. In the present study, NGAL was analyzed at both transcript and protein levels in different cancer types by analysing 38 public available microarray datasets and the Human Protein Atlas tool. NGAL transcripts were significantly higher in the majority of solid tumors compared to the relative normal tissues for every dataset analyzed. Furthermore, concordance of NGAL at both mRNA and protein levels was observed for 6 cancer types including bladder, colorectal, liver, lung, ovarian, and pancreatic. All metastatic tumors showed a decrease of NGAL expression when compared to matched primary lesions. According to these results, NGAL is a candidate marker for tumor growth in a fraction of solid tumors. Further investigations are required to elucidate the function of NGAL in tumor development and metastatic processes.

Pulmonary arterial hypertension is a severe progressive disease with marked morbidity and high mortality in which right ventricular (RV) failure is the major cause of death. Thus knowledge of the mechanisms underlying RV failure is an area of active interest. Previous studies suggest a role of NADPH oxidase in cardiomyocyte dysfunction in the left heart. Here we postulate that acute pressure overload induced by pulmonary artery banding (PAB) leads to a Nox4-initiated increase in reactive oxygen species (ROS) in mouse RV that may lead to feed-forward induction of Nox2. To test our hypothesis, ROS production was measured in RV and left ventricle homogenates. The data show that hydrogen peroxide (H2O2), but not superoxide anion (O2·−), was increased in the early phases (within 6 h) of PAB in RV and that this increase was diminished by catalase and diphenyleneiodonium chloride but not by SOD, Nω-nitro-l-arginin methyl ester, febuxostat, or indomethacin. H2O2 production in RV was not attenuated in Nox2 null mice subjected to 6 h PAB. Moreover, we observed an upregulation of Nox4 mRNA after 1 h of PAB and an increase in mitochondrial Nox4 protein 6 h post-PAB. In contrast, we observed an increase in Nox2 mRNA 1 day post-PAB. Expression of antioxidant enzymes SOD, catalase, and glutathione peroxidase did not change, but catalase activity increased 6 h post-PAB. Taken together, these findings show a role of mitochondria-localized Nox4 in the early phase of PAB and suggest an involvement of this isozyme in early ROS generation possibly contributing to progression of RV dysfunction and failure.

Aim of the study: Colorectal cancer (CRC) is one of the leading cause of death in European population. It progresses without any symptoms in the early stages or those clinical symptoms are very discrete. The aim of this study was a retrospective analysis of treatment outcomes in patients with colorectal cancer complicated with intestinal perforation. Material and methods: A retrospective analysis of patients urgently operated upon in our Division of General Surgery, because of large intestine perforation, from February 1993 to February 2013 has been made. Results were compared with a group of patients un dergoing the elective surgery for colorectal cancer in the same time and Division. Results: Intestinal perforation occurred more often in males (6.52% vs. 6.03%), patients with mucous component in histopathological examination (9.09% vs. 6.01%) and with clinicaly advanced CRC. Patients treated because of perforation had a five-fold higher 30 day mortality rate (9.09% vs. 1.83%), however long-term survival did not differ significantly in both groups. After resectional surgery in 874 patients an in testinal anastomosis was made. Anastomotic leakage was present in 23 (2.6%) patients. This complication occurred six-fold more frequently in a group of patients operated upon because of intestinal perforation (12.20% vs. 2.16%). Conclusions: In patients with CRC complicated with perforation of the colon in a 30-day observation significantly higher rate of complications and mortality was shown, whereas there was no difference in distant survival rates.

Introduction: Coronary artery disease (CAD) has been a leading cause of death in the western world for the last few decades, despite significant improvements in treatment and management. Diagnostic algorithms for the evaluation of patients with suspected CAD are based on available guidelines. Aim: To evaluate the impact of geographical distances to coronary angiography laboratories on the patient evaluation pathways in patients with suspected CAD, from a population-based study in Hungary. Material and methods: Depersonalised data of 29,202 patients identified by their pseudo-social security number were analysed. All patients underwent coronary angiography as an initial direct invasive investigation (DI) following an at least half-year-long stable period between 1 January 2004 and 31 December 2008. Results: One hundred and thirty-five dominant primary cardiology centres (PCC) have been identified, from which 85 proved to have sample size more than 100 DIs in tertiary cardiology centres (TCC). The frequency of DIs showed a close correlation with PCC-TCC distances (r = –0.44, p < 0.001). A negative correlation could be demonstrated between the age of patients and PCC-TCC distances (r = –0.45, p < 0.001). Without significant change in the absolute mortality, the relative mortality increased with the increase in PCC-TCC distance (r = 0.25, p < 0.05). Conclusions: The PCC-TCC distance has an important effect on patient pathways in subjects with suspected CAD.