Higher Relative Risk Of Death Research Articles

Changes in hospital mortality in patients with cancer during the COVID-19 pandemic (ISARIC-CCP-UK): a prospective, multicentre cohort study

Patients with cancer are at greater risk of dying from COVID-19 than many other patient groups. However, how this risk evolved during the pandemic remains unclear. We aimed to determine, on the basis of the UK national pandemic protocol, how factors influencing hospital mortality from COVID-19 could differentially affect patients undergoing cancer treatment. We also examined changes in hospital mortality and escalation of care in patients on cancer treatment during the first 2 years of the COVID-19 pandemic in the UK. We conducted a prospective cohort study of patients aged older than 19 years and admitted to 306 health-care facilities in the UK with confirmed SARS-CoV-2 infection, who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol (CCP) across the UK from April 23, 2020, to Feb 28, 2022; this analysis included all patients in the complete dataset when the study closed. The primary outcome was 30-day in-hospital mortality, comparing patients on cancer treatment and those without cancer. The study was approved by the South Central-Oxford C Research Ethics Committee in England (Ref: 13/SC/0149) and the Scotland A Research Ethics Committee (Ref 20/SS/0028), and is registered on the ISRCTN Registry (ISRCTN66726260). 177 871 eligible adult patients either with no history of cancer (n=171 303) or on cancer treatment (n=6568) were enrolled; 93 205 (52·4%) were male, 84 418 (47·5%) were female, and in 248 (13·9%) sex or gender details were not specified or data were missing. Patients were followed up for a median of 13 (IQR 6-21) days. Of the 6568 patients receiving cancer treatment, 2080 (31·7%) died at 30 days, compared with 30 901 (18·0%) of 171 303 patients without cancer. Patients aged younger than 50 years on cancer treatment had the highest age-adjusted relative risk (hazard ratio [HR] 5·2 [95% CI 4·0-6·6], p<0·0001; vs 50-69 years 2·4 [2·2-2·6], p<0·0001; 70-79 years 1·8 [1·6-2·0], p<0·0001; and >80 years 1·5 [1·3-1·6], p<0·0001) but a lower absolute risk (51 [6·7%] of 763 patients <50 years died compared with 459 [30·2%] of 1522 patients aged >80 years). In-hospital mortality decreased for all patients during the pandemic but was higher for patients on cancer treatment than for those without cancer throughout the study period. People with cancer have a higher risk of mortality from COVID-19 than those without cancer. Patients younger than 50 years with cancer treatment have the highest relative risk of death. Continued action is needed to mitigate the poor outcomes in patients with cancer, such as through optimising vaccination, long-acting passive immunisation, and early access to therapeutics. These findings underscore the importance of the ISARIC-WHO pandemic preparedness initiative. National Institute for Health Research and the Medical Research Council.

Assotiation of testosterone levels and oxidative stress activity with 10-year survival in men with cardiac resynchronization therapy

Aim. To investigate the association of testosterone levels (TES) and oxidative stress activity with 10-year survival in men with cardiac resynchronization therapy (CRT).Methods. 86 men with CRT (59.0±9.8 years; 66.3% ischemic cardiomyopathy) were divided into 4 groups: Gr.1 (n=19) TES&lt;median level (16.4nmol/l) + myeloperoxidase (MPO) &lt; median level (32.5 ng/mL); Gr.2 (n=18) TES&lt;median level + MPO&gt;median level; Gr.3 (n=23) TES&gt; medians + MPO &lt; median level; Gr.4 (n=26) TES &gt; median level + MPO &gt; median level. Echocardiography parameters, incidence of ventricular extrasystole, TES in plasma, estradiol, progesterone, dehydroepiandrosterone sulfate, norepinephrine, MPO, NT-proBNP, matrix metalloproteinase, tissue inhibitor of metalloproteinase were assessed. Prognostic level of NT-proBNP was assessed by ROC analysis; 10-year survival was measured by Kaplan-Meier method, factors associated with it were evaluated using Cox regression.Results. The majority of patients were NYHA II and NYHA III for Gr. 3 and Gr.4 respectively (р3-4=0,010). At baseline: there was no difference in echocardiography parameters, levels of NT-proBNP, MPO, steroids, matrix metalloproteinase between groups; tissue inhibitor of metalloproteinase was higher in Gr.2 and Gr.4; the highest norepinephrine levels was in Gr.4. Follow-up: reverse cardiac remodeling was associated with NT-proBNP decreasing and was registered in Gr.4 and Gr. 3. The level of MPO was decreased in Gr.3, Gr.4., and was the highest in Gr.4. The level of estradiol was increased in Gr.1; There were no difference in hormone levels in Gr.2. TES, dehydroepiandrosterone sulfate was increased, but progesterone was decreased in Gr.3 and in Gr.4. The norepinephrine`s levels were increased in all groups. The number of ventricular extrastimuli was increased in Gr.4. Predictive level of NT-proBNP was 756.0 pg/ml (AUC=0.685; p=0.003; sensitivity: 64%, specificity: 68%). The 10-year survival rate was 15.4%; 33.5%; 76.3%; 24.4% for Gr. 1-4 respectively (Log Rank test: Gr.1-2=0.378; Gr.1-3&lt;0.001; Gr.1-4=0.070; Gr.2-3=0.009; Gr.2-4=0.772; Gr.3-4=0.010). The survivance was higher in patients with the best CRT response time (p=0.004), the level of NT-proBNP&gt;756.0 pg/ml (p=0.001) in Gr.1, Gr.2; the best CRT response time (p=0.001), left ventricular ejection fraction (p=0.046), MPO&gt;median (p=0.041), amiodarone administration (0.008) in Gr. 3, Gr. 4.Conclusion. CRT modulates steroidogenesis. Increase of TES and dehydroepiandrosterone sulfate with lower oxidative stress activity is associated with greater reverse cardiac remodeling and better 10-year survival rate. The higher level of TES and simultaneously MPO more than 32.5 pg/ml were related to less reverse cardiac remodeling, higher rate of amiodarone administration by 5.2 times, increasment of ventricular arrhythmias rate and higher relative risk of death by 4.2 times. Relationship between 10-year survival rate and period of best CRT response indicates less physiological nature of forceful modulating effects of CRT.

CLINICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH SEVERE COVID-19 AND CIRRHOSIS OR LIVER TRANSPLANT IN A BRAZILIAN QUATERNARY CENTER.

Specific associations between liver cirrhosis and liver transplant with poorer outcomes in COVID-19 are still not completely clear. We aimed to evaluate the clinical characteristics and outcomes of patients with severe COVID-19 and cirrhosis or liver transplant in Sao Paulo, Brazil. A retrospective observational study was conducted in a quaternary hospital. Patients with COVID-19 and liver cirrhosis or liver transplant were selected. The clinical and demographic characteristics, as well as the outcomes, were assessed using electronic records. A total of 46 patients with COVID-19 and liver condition were included in the study. Patients with liver cirrhosis had significantly more endotracheal intubation and a higher relative risk of death than liver transplant recipients. Patients with higher MELD-Na scores had increased death rates and lower survival probability and survival time. Patients with liver cirrhosis, especially those with higher MELD-Na scores, had poorer outcomes in COVID-19. Liver transplant recipients do not seem to be linked to poorer COVID-19 outcomes.

Lung cancer mortality trends among women across Spain: the role of birth cohorts in diverging regional patterns

Smoking among Spanish women has increased during the last 50 years and is considered by some authors a modern epidemic. However, mortality risk by cohorts may differ at a regional level, given that health inequalities (and the determinants of smoking and its consequences) are regionally patterned. We applied an Age-Period-Cohort model to identify birth cohort effects on female lung cancer mortality in Spain. We found a strong linear increase in lung cancer mortality during the 1980–2019 period in all regions. Cohorts born between 1935 and 1955 presented a higher relative risk of death at a national and subnational level. However, we found diverging cohort patterns across regions afterward, with some regions presenting a slight mortality improvement (or stagnation) in their youngest cohorts, while in other regions mortality kept increasing. This suggests that inequalities in lung cancer mortality in Spain among women are not only generationally based, but that generational risks also vary across space. Some of the regions that presented improvements in mortality among its younger cohorts are Madrid, Navarra, and the Basque Country, which are some of the wealthiest in the Country. While speculative, this could imply that improvements at a regional level might be associated with factors related to structural conditions that result in the adoption of healthy behaviors.

Exploring the Prognostic and Predictive Roles of Ki-67 in Endometrial Cancer

Background: Up to now, endometrial cancer (EC) treatments are mainly represented by surgery followed by adjuvant chemotherapy or radiotherapy. The updated guidelines give a 2A recommendation for the use of hormone therapy only in advanced low-grade ECs, underlying the need for more data on the role of hormone therapy in the adjuvant setting. Methods: The clinicopathological data of 158 early-stage EC patients was retrospectively collected. A Ki-67 cut-off value of 40% was established based on literature data. Disease-free survival (DFS) and Overall survival (OS) were evaluated. Results: Results: Multivariate analysis of DFS and OS showed a significantly increased risk of progression in patients with &gt;40% Ki-67 [HR = 3.13 (95% CI; 1.35–7.14); p = 0.007] and a significantly higher relative risk of death [HR = 3.70 (95% CI; 1.69–8.33); p = 0.001]. The predictive role of the Ki-67 index was highlighted by the clinical benefit of adjuvant hormone in patients with high Ki-67. Conclusions: Our results suggest a positive role of the Ki-67 index as a prognostic and potentially predictive marker in EC, although further studies are warranted to reach a definitive conclusion.

Urinary peptides provide information about the risk of mortality across a spectrum of diseases and scenarios

BackgroundThere is evidence of pre-established vulnerability in individuals that increases the risk of their progression to severe disease or death, although the mechanisms causing this are still not fully understood. Previous research has demonstrated that a urinary peptide classifier (COV50) predicts disease progression and death from SARS-CoV-2 at an early stage, indicating that the outcome prediction may be partly due to vulnerabilities that are already present. The aim of this study is to examine the ability of COV50 to predict future non-COVID-19-related mortality, and evaluate whether the pre-established vulnerability can be generic and explained on a molecular level by urinary peptides.MethodsUrinary proteomic data from 9193 patients (1719 patients sampled at intensive care unit (ICU) admission and 7474 patients with other diseases (non-ICU)) were extracted from the Human Urinary Proteome Database. The previously developed COV50 classifier, a urinary proteomics biomarker panel consisting of 50 peptides, was applied to all datasets. The association of COV50 scoring with mortality was evaluated.ResultsIn the ICU group, an increase in the COV50 score of one unit resulted in a 20% higher relative risk of death [adjusted HR 1.2 (95% CI 1.17–1.24)]. The same increase in COV50 in non-ICU patients resulted in a higher relative risk of 61% [adjusted HR 1.61 (95% CI 1.47–1.76)], consistent with adjusted meta-analytic HR estimate of 1.55 [95% CI 1.39–1.73]. The most notable and significant changes associated with future fatal events were reductions of specific collagen fragments, most of collagen alpha I (I).ConclusionThe COV50 classifier is predictive of death in the absence of SARS-CoV-2 infection, suggesting that it detects pre-existing vulnerability. This prediction is mainly based on collagen fragments, possibly reflecting disturbances in the integrity of the extracellular matrix. These data may serve as a basis for proteomics-guided intervention aiming towards manipulating/ improving collagen turnover, thereby reducing the risk of death.

Physical activity and diabetes mortality in people with type 2 diabetes: a prospective cohort study of 0.5 million US people

AimTo examine the association between physical activity and the cause of death with the greatest risk related to type 2 diabetes mellitus (T2DM) in a large population-based cohort representative of the general US adult population. MethodsA total of 41,726 adults suffering from T2DM (age 62 ± 14 years) and 459,660 adults without diabetes (age 46 ± 18 years) who participated in the National Health Interview Survey from 1997 to 2014 were included in this prospective cohort study. Self-reported moderate-to-vigorous physical activity (MVPA) was categorized into inactive, insufficiently active, active and very active. Mortality data was obtained from the National Death Index. Cox regression models adjusted for potential confounders were performed to estimate hazard ratio (HR) and 95% confidence interval (CI). ResultsDiabetes mortality cause showed the highest relative risk of death among adults with T2DM compared to adults without diabetes (HR 5.72 [3.15;10.39]). There was a non-linear inverse dose-response association between MVPA and diabetes mortality among adults with T2DM, up to a plateau in risk reduction at approximately 500 min/week. Any level of activity was inversely associated with a significantly lower risk of diabetes mortality compared with being inactive (insufficiently active HR 0.71[0.54;0.97], active HR 0.68 [0.49;0.95], very active HR 0.44 [0.32;0.60]). Compared to adults without diabetes, the risk of diabetes mortality decreased from HR 7.38 [4.00;13.58] for inactive people with T2DM to HR 3.34 [1.76;6.32] for very active people with T2DM. ConclusionsHigher levels of MVPA were associated with lower risk of diabetes mortality among adults with T2DM.

Age-Related Association between Multimorbidity and Mortality in US Veterans with Incident Chronic Kidney Disease

Introduction: Mortality is an important long-term indicator of the public health impact of chronic kidney disease (CKD). We investigated the role of individual comorbidities and multimorbidity on age-specific mortality risk among US veterans with new-onset CKD. Methods: The cohort included 892,005 veterans aged ≥18 years with incident CKD stage 3 between January 2004 and April 2018 in the US Veterans Health Administration (VHA) system and followed until death, December 2018, or up to 10 years. Incident CKD was defined as the first-time estimated glomerular filtration rate (eGFR) was <60 mL/min/1.73 m² for >3 months. Comorbidities were ascertained using inpatient and outpatient clinical records in the VHA system and Medicare claims. We estimated death rates for any cardiovascular disease (CVD, a composite of 6 CVD conditions) and 15 non-CVD comorbidities, and adjusted risks of death (hazard ratio [HR], 95% confidence interval [CI]) overall and by age group at CKD incidence. Results: At CKD incidence, the mean age was 72 years, and 97% were male; the mean eGFR was 52 mL/min/1.73 m², and 95% had ≥2 comorbidities (median, 4) in addition to CKD. During a median follow-up of 4.5 years, among the 16 comorbidities, CVD was associated with the highest relative risk of death in younger veterans (HR 1.96 [95% CI: 1.61–2.37] in ages 18–44 years and HR 1.66 [1.63–1.70] in ages 45–64 years). Dementia was associated with the highest relative risk of death among older veterans (HR 1.71 [1.68–1.74] in ages 65–84 years and HR 1.69 [1.65–1.73] in ages 85–100 years). The additive effect of multimorbidity on risk of death was stronger in younger than older veterans. Compared to having 1 or no comorbidity at CKD onset, the risk of death with ≥5 comorbidities was >7-fold higher among veterans aged 18–44 years and >2-fold higher among veterans aged 85–100 years. Conclusion: The large burden of comorbidities in US veterans with newly identified CKD places them at the risk of premature death. Compared with older veterans, younger veterans with multiple comorbidities, particularly with CVD, at CKD onset are at an even higher relative risk of death.

Impact of busulfan pharmacokinetics on outcome in adult patients receiving an allogeneic hematopoietic cell transplantation

Busulfan (Bu) is widely used in conditioning regimens before allogeneic hematopoietic cell transplantation, with variable metabolism due to interindividual differences of pharmacokinetics (PK). The purpose of this study was to correlate pharmacokinetics and clinical outcomes. Lower-AUC, in range-AUC and higher-AUC were defined as ±25% of the targeted Bu-AUC. In 2019, we changed Bu dosing from 4×/day (Bu-4) to 1×/day (Bu-1) for ease of application. AUC-target range was reached in 46% of patients; 40% were in low-AUC and 14% in high-AUC. Among all toxicities, viral and fungal infections were significantly more frequent in high-AUC compared with low-AUC (20% vs. 8%; p = 0.01 and 37% vs. 17%; p = 0.03). Bu-1 showed lower PK values (66% vs. 36% of Bu-4 in low-AUC; p < 0.01) and higher incidence of mucositis (p = 0.02). Long-term outcomes at 2 years showed a higher non-relapse mortality (NRM) (p < 0.01) and higher relative risk of death in the high-AUC group compared to the other groups. Cumulative incidence of relapse and acute/chronic GvHD were not significantly different. The optimal cut-off in Bu-AUC associated with low NRM was 969 µmol/l*min (ROC AUC 0.67, sensitivity 0.86 and specificity 0.47) for Bu-4. In conclusion, low-AUC BU-PK seems of benefit regarding NRM and survival.

Hypoalbuminaemia as a Prognostic Biomarker of First-Line Treatment Resistance in Metastatic Non-small Cell Lung Cancer.

Introduction: Despite significant advances in systemic anticancer therapy (SACT) for non-small cell lung cancer (NSCLC), many patients still fail to respond to treatment or develop treatment resistance. Albumin, a biomarker of systemic inflammation and malnutrition, predicts survival in many cancers. We evaluated the prognostic significance of albumin in patients receiving first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC.Methods: All patients treated with first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC at a regional Scottish cancer centre were identified. Serum albumin at pre-treatment, after 12-weeks of treatment, and at the time of progressive disease were recorded. The relationship between albumin (≥ 35g/L v <35g/L) and overall survival (OS) was examined.Results: Data were available for 389 patients of both targeted therapy cohort (n = 159) and immunotherapy-based therapy cohort (n = 230). Pre-treatment albumin was predictive of OS in each cohort at HR1.82 (95%CI 1.23–2.7) (p =0.003) and HR2.55 (95%CI 1.78–3.65) (p < 0.001), respectively. Pre-treatment albumin <35 g/L was associated with a significantly higher relative risk of death within 12 weeks in each cohort at RR9.58 (95%CI 2.20–41.72, p = 0.003) and RR3.60 (95%CI 1.74–6.57, p < 0.001), respectively. The 12-week albumin was predictive of OS in each cohort at HR1.88 (95%CI 1.86–4.46) (p < 0.001) and HR2.67 (95%CI 1.74–4.08) (p < 0.001), respectively. 46 out of 133 (35%) evaluable patients treated with targeted therapy and 43 out of 169 (25%) treated with immunotherapy-based therapy crossed over albumin prognostic groups between pre-treatment and 12-week. The prognostic value of 12-week albumin was independent of pre-treatment albumin status. A majority of patients had albumin <35g/L at the time of progressive disease when it was also predictive of survival following progressive disease at HR2.48 (95%CI 1.61–3.82) (p < 0.001) and HR2.87 (95%CI 1.91–4.31) (p < 0.001) respectively).Conclusions: Albumin is a reliable prognostic factor in patients with metastatic NSCLC, predicting survival independent of the class of drug treatment at various time points during the patient journey. Tracking albumin concentrations during systemic therapy may indicate disease activity or treatment response over time.

Factors associated with inflamm-aging in institutionalized older people

The increase in inflammatory cytokines associated with a reduction in the bioavailability of zinc has been used as a marker for inflammation. Despite the high inflammatory state found in institutionalized older individuals, few studies have proposed verifying the factors associated with this condition in this population. To verify the factors associated with inflamm-aging in institutionalized older people. A total of 178 older people (≥ 60 years old) living in nursing homes in Natal/RN were included in the study. Cluster analysis was used to identify three groups according to their inflammatory state. Analysis anthropometric, biochemical, sociodemographic, and health-related variables was carried out. In sequence, an ordinal logistic regression was performed for a confidence level of 95% in those variables with p < 0.20 in the bivariate analysis. IL-6, TNF-α, zinc, low-density lipids (LDL), high-density lipids (HDL), and triglycerides were associated with inflamm-aging. The increase of 1 unit of measurement of LDL, HDL, and triglycerides increased the chance of inflammation-aging by 1.5%, 4.1%, and 0.9%, respectively, while the oldest old (≥ 80 years old) had an 84.9% chance of presenting inflamm-aging in relation to non-long-lived older people (< 80 years). The association between biochemical markers and inflamm-aging demonstrates a relationship between endothelial injury and the inflammatory state. In addition, the presence of a greater amount of fat in the blood may present a higher relative risk of death.

Epidemiology and clinical course of SARS-CoV-2 infection in cancer patients in the Veneto Oncology Network during the first and second pandemic waves.

6511 Background: Since the beginning of the COVID-19 outbreak, the Veneto Oncology Network ROV licensed dedicated guidelines for cancer patients care during the pandemic, and developed a regional registry (ROVID) aimed at describing epidemiology and clinical course of SARS-CoV-2 infection in cancer patients. Preliminary data on 170 patients mainly diagnosed during the first pandemic wave have been published (Guarneri V, Eur J Cancer 2021). Here we report the data of additional 270 patients, comparing clinical data and outcomes between first (W1) and second (W2) pandemic waves. Methods: All patients with cancer diagnosis and documented SARS-CoV-2 infection are eligible. Data on diagnosis, comorbidities, anticancer treatments, details on SARS-CoV-infection including source of contagion, clinical presentation, hospitalization, treatments and fate of the infection are recorded. Results: 440 patients have been enrolled, 196 diagnosed during W1 (until September 2020) and 244 during W2. The most common cancer type was breast cancer (n = 116). Significant differences in clinical characteristics between W1 and W2 were the followings: ECOG PS 0 (34% vs 58%), presence of cardiac comorbidities (30% vs 13%), presence of any co-morbidities (81% vs 62%), smoking habits (23% vs 13%). Patients diagnosed in W1 were less likely on active anticancer therapy (54% vs 73%) at the time of SARS-CoV-2 infection. Distribution per stage, presence of lung metastases, disease setting (curative vs palliative), active treatment discontinuation due to infection were similar between W1 and W2. Patients diagnosed in W1 were more likely symptomatic for SARS-CoV-2 infection (80% vs 67%), and reported more frequently an in-hospital contact as potential source of infection (44% vs 9%). Significantly more patients diagnosed in W1 were hospitalized (76% vs 25%). All-cause mortality rates were 30.6% for patients diagnosed in W1 vs 12% for patients diagnosed in W2 (p &lt; 0.001). However, deaths due to SARS-CoV-2 infection were more frequent in patients diagnosed in W2 (86% vs 54%, odds ratio 3.22; 95% CI 1.97-5.279). Conclusions: Differences in clinical characteristics between W1 and W2 reflect different pattern of virus circulation. The dramatic reduction of in-hospital contact as a source of infection reflects the efforts put in place to protect this vulnerable population from in-hospital exposure. The lower all-cause mortality rate observed in W2 is in line with the observed less frail population. However, the higher relative risk of death due to SARS-CoV-2 infection observed in W2 reinforces the need to adopt protective measures including vaccination in cancer patients, irrespectively of age, stage, and comorbidities.

Proposing the VetCompass clinical grading tool for heat-related illness in dogs

Heat-related illness is a potentially fatal condition in dogs. Rapid and accurate recognition of the severity can improve clinical management in affected dogs and lead to better outcomes. This study explored retrospective VetCompass veterinary clinical records to investigate the clinical signs recorded for dogs presenting with heat-related illness to primary-care veterinary practice from 2016 to 2018. The relative risk of death associated with these clinical signs was reported and used to develop a novel clinical grading tool. From the clinical records of 856 heat-related illness events, the most frequently recorded clinical signs were respiratory changes (68.73%) and lethargy (47.79%). The clinical signs with the highest relative risk of death were neurological dysfunction, gastrointestinal haemorrhage and bleeding disorders. The novel VetCompass Clinical Grading Tool for Heat-Related Illness in dogs defines three grades: mild (altered respiration, lethargy), moderate (gastrointestinal signs, a single seizure, episodic collapse) and severe (neurological dysfunction, gastrointestinal haemorrhage, bleeding disorders). This novel grading tool offers a simple, evidence-based device to improve recognition of heat-related illness in dogs and promote improved decision-making for earlier interventions such as cooling and hospitalisation. This could improve outcomes and protect the welfare of dogs in the face of rising global temperatures.

Early Do-Not-Resuscitate Orders and Outcome After Intracerebral Hemorrhage.

Do-not-resuscitate (DNR) orders are commonly used after intracerebral hemorrhage (ICH) and have been shown to be a predictor of mortality independent of disease severity. We determined the frequency of early DNR orders in ICH patients and whether a previously reported association with increased mortality still exists. We performed a retrospective analysis of patients discharged from non-federal California hospitals with a primary diagnosis of ICH from January 2013 through December 2014. Characteristics included hospital ICH volume and type and whether DNR order was placed within 24h of admission (early DNR order). The risk of in-hospital mortality was evaluated both on the individual and hospital level using multivariable analyses. A case mix-adjusted hospital DNR index was calculated for each hospital by comparing the actual number of DNR cases with the expected number of DNR cases from a multivariate model. A total of 9,958 patients were treated in 180 hospitals. Early DNR orders were placed in 20.1% of patients and 54.2% of these patients died during their hospitalization compared to 16.0% of patients without an early DNR order. For every 10% increase in a hospital's utilization of early DNR orders, there was a corresponding 26% increase in the likelihood of in-hospital mortality. Patients treated in hospitals within the highest quartile of adjusted DNR use had a higher relative risk of death compared to the lowest quartile (RR 3.9 vs 5.2) though the trend across quartiles was not statistically significant. The use of early DNR orders for ICH continues to be a strong predictor of in-hospital mortality. However, patients treated at hospitals with an overall high or low use of early DNR had similar relative risks of death whether or not there was an early DNR order, suggesting that such orders may not be a proxy for less aggressive care as seen previously.

Pelvic injury patterns in blast: Morbidity and mortality.

Pelvic trauma has emerged as one of the most severe injuries to be sustained by the victim of a blast insult. The incidence and mortality due to blast-related pelvic trauma is not known, and no data exist to assess the relative risk of clinical or radiological indicators of mortality. The UK Joint Theater Trauma Registry was interrogated to identify those sustaining blast-mediated pelvic fractures during the conflicts in Iraq and Afghanistan, from 2003 to 2014, with subsequent computed tomography image analysis. Casualties that sustained more severe injuries remote to the pelvis were excluded. One hundred fifty-nine casualties with a 36% overall mortality rate were identified. Pelvic vascular injury, unstable pelvic fracture patterns, traumatic amputation, and perineal injury were higher in the dismounted fatality group (p < 0.05). All fatalities sustained a pelvic vascular injury. Pelvic vascular injury had the highest relative risk of death for any individual injury and an associated mortality of 56%. Dismounted casualties that sustained unstable pelvic fracture patterns, traumatic amputation, and perineal injury were at three times greater risk (relative risk, 3.00; 95% confidence interval, 1.27-7.09) to have sustained a pelvic vascular injury than those that did not sustain these associated injuries. Opening of the pubic symphysis and at least one sacroiliac joint was significantly associated with pelvic vascular injury (p < 0.001), and the lateral displacement of the sacroiliac joints was identified as a fair predictor of pelvic vascular injury (area under the receiver operating characteristic curve, 0.73). Dismounted blast casualties with pelvic fracture are at significant risk of a noncompressible pelvic vascular injury. Initial management of these patients should focus upon controlling noncompressible pelvic bleeding. Clinical and radiological predictors of vascular injury and mortality suggest that mitigation strategies aiming to attenuate lateral displacement of the pelvis following blast are likely to result in fewer fatalities and a reduced injury burden. Prognostic, level III.

Short-term and long-term prognosis in patients with Q-myocardial infarction complicated by acute heart failure with hyperglycemia

The aim was to study the short-term and long-term prognosis in patients with Q- myocardial infarction (Q-MI) complicated by acute heart failure (AHF) with hyperglycemia (HG).Materials and methods. In total, 108 patients with Q-MI complicated by AHF with HG were examined. The mean age was 67 (60; 78) years, male – 55.5 %. Using the Kaplan-Meyer method of multiple assessments and the Cox proportional risk model, the effects of HG on admission, patients’ age and Q-MI therapy on the relative risk (RR) of in-hospital mortality, one-year mortality, re-hospitalization and total cumulative endpoint (CE) were estimated.Results. The level of HG on admission >10.3 mmol / l significantly increased the RR of total CE by 2.1 times (CI 1.1960–3.6012, P = 0.009); >9.0 mmol / l increased the RR of in-hospital mortality by 5.78 times (BP 1.109, CI 1.322–25.293, P = 0.02) and one-year mortality by 4.75 times (CI 1.64–13.74, P = 0.004). Patients older than 67 years had a higher RR of death within one year by 4 % (1.042 BP, CI 1.0048–1.0810, P = 0.03). Systemic thrombolytic therapy (STLT) reduced the RR of achieving total CE by 73 % (BP 0.27, CI 0.0984–0.7590, P = 0.01), s-blockers by 60 % (BP 0.40, CI 0.2310–0.7380, p = 0.002) and AMR – by 49 % (BP 0.51 CI 0.2749–0.9288, P = 0.03). The use of eplerenone reduced the RR of total CE compared with spironolactone (OR 0.26, CI 0.1001–0.6706, P = 0.006). Patients who received AMR at a dose of 50 mg had a 2.9-fold (CI 1.0332–8.3100, P = 0.04) higher RR to achieve total CE compared with a dose of 25 mg. Using of inotropes increased the RR of total CE by 3.1 times (CI 1.7495–5.4981, P 9 mmol/l significantly increases the risk of in-hospital mortality and death within one year in patients with Q-MI, complicated by AHF, and over 10.3 mmol / l – the risk of achieving total CE. The age of patients older than 67 years significantly increases the RR of one-year mortality. STLT and pharmacotherapy including s-blockers reduces the risk of in-hospital mortality, one-year mortality and achieve total CE. The development of clinical conditions requiring the use of inotropic support in patients with AMI complicated by AHF and HG increases the relative risk of in-hospital mortality, one-year mortality and total CE. Using the drugs of ACE inhibitors or ARBs groups and statins at average maintaining doses reduces the risk of in-hospital mortality and one-year mortality. The pharmacotherapy of Q-MI complicated by AHF with HG including AMR decreases the risk of achieving total CE and re-hospitalization. The use of AMR at a dose of 50 mg compared with a dose of 25 mg increases the risk of achieving total CE, and eplerenone has advantages over spironolactone.

Characteristics of patients with preeclampsia and eclampsia in a tertiary teaching hospital in India

The aim of our study was to identify preoperative risk factors affecting overall survival after cardiac retransplantation (ReTX) in a contemporary era.The United Network for Organ Sharing database was used to identify patients undergoing ReTX between 1995 and 2012. Of the total 28,464 primary transplants performed, 987 (3.5%) were retransplants. The primary outcome investigated was overall survival. The influence of preoperative donor and recipient characteristics on survival were then tested with univariate logistic regression and multivariate Cox regression models.Of 987 patients who underwent ReTX, median survival was 9 years. Estimated survival at 1, 3, 5, 10, and 15 years following retransplant was 80% (95% confidence interval [CI], 78%-83%), 70% (95% CI, 67%-73%), 64% (95% CI, 61%-67%), 47% (95% CI, 43%-51%), and 30% (95% CI, 25%-37%), respectively. Clinical predictors of survival using multivariable analysis included donor age (relative risk [RR], 1.14; P = .004), ischemic time > 4 hours (RR, 1.48; P = .004); preoperative support with extracorporeal membrane oxygenator (RR, 3.91; P < .001), and the time between previous and current transplant (P = .004). Patients with ReTX have 1.27 times higher relative risk of death compared with patients undergoing primary transplant only (RR, 1.27; 95% CI, 1.13-1.42; P < .001).Patients who undergo cardiac ReTX can expect to have a 1-year survival less than a patient undergoing primary transplant with an acceptable median overall survival. Both donor and recipient preoperative factors contribute to overall survival following cardiac ReTx. Donor characteristics include age of the donor and ischemic time. Recipient factors include the need for extracorporeal membrane oxygenator and the number of days between the first and second transplant. Optimal survival following cardiac ReTX can best be predicted by choosing patients who are farther out from their initial transplant, not dependent upon preoperative extracorporeal support, and by choosing donor hearts younger in age and those likely to have shorter ischemic times.

Low ERCC1 expression is a good predictive marker in lung adenocarcinoma patients receiving chemotherapy based on platinum in all TNM stages - a single-center study

BackgroundHigh ERCC1 expression is thought to be related with resistance to chemotherapy based on platinum. The aim of this study was to present our institutional observations regarding to the association of ERCC1 and overall survival (OS) of the lung adenocarcinoma patients who received chemotherapy based on platinum.Material/methodsA total of 253 lung adenocarcinoma patients in all TNM stages were retrospectively investigated. The diagnosis was based on small biopsy samples obtained during bronchoscopy. Depending on the TNM stage of the disease and clinical condition, patients received only the chemotherapy based on platinum, or in combination with radiotherapy or surgery. Tissue sample for ERCC1 immunohistochemical analysis was sufficient in 129 patients. Low from high ERCC1 expression was separated by the semi-quantitative H-score median.ResultsHigh ERCC1 expression was found in 47.3% patients, and was correlated with higher TNM (p = 0.021), tumor enlargement (p = 0.002), positive lymph nodes (p = 0.001), positive distant metastasis (p = 0.005), and higher relative risk of death (p < 0.001). Furthermore, significance association was observed for low ERCC1 expression and better performance status (ECOG) (p = 0.023). Longer OS was strongly associated with a low ERCC1 expression, not only in the group of patients in TNM stage I-III, who were treated with combination of chemotherapy with surgery or radiotherapy (p = 0.002), but also in the group of patients in TNM stage IV who received only chemotherapy based on platinum (p < 0.001), compared with the patients in the same TNM stage and high ERCC1 expression.ConclusionsERCC1 expression in lung adenocarcinoma is a useful prognostic marker and moreover, a useful predictive marker in patients receiving chemotherapy based on platinum in all stages of the disease.

Association of Diabetes With All-Cause and Cause-Specific Mortality in Asia

Asia is home to the largest diabetic populations in the world. However, limited studies have quantified the association of diabetes with all-cause and cause-specific mortality in Asian populations. To evaluate the association of diabetes with all-cause and cause-specific mortality in Asia and to investigate potential effect modifications of the diabetes-mortality associations by participants' age, sex, education level, body mass index, and smoking status. This pooled analysis incorporated individual participant data from 22 prospective cohort studies of the Asia Cohort Consortium conducted between 1963 and 2006. A total of 1 002 551 Asian individuals (from mainland China, Japan, South Korea, Singapore, Taiwan, India, and Bangladesh) were followed up for more than 3 years. Cohort-specific hazard ratios and 95% confidence intervals for all-cause and cause-specific mortality were estimated using Cox regression models and then pooled using random-effects meta-analysis. Analysis was conducted between January 10, 2018, and August 31, 2018. Doctor-diagnosed diabetes, age, sex, education level, body mass index, and smoking status. All-cause and cause-specific mortality. Of 1 002 551 participants (518 537 [51.7%] female; median [range] age, 54.0 [30.0-98.0] years), 148 868 deaths were ascertained during a median (range) follow-up of 12.6 (3.0-38.9) years. The overall prevalence of diabetes reported at baseline was 4.8% for men and 3.6% for women. Patients with diabetes had a 1.89-fold risk of all-cause death compared with patients without diabetes (hazard ratio [HR], 1.89; 95% CI, 1.74-2.04), with the highest relative risk of death due to diabetes itself (HR, 22.8; 95% CI, 18.5-28.1), followed by renal disease (HR, 3.08; 95% CI, 2.50-3.78), coronary heart disease (HR, 2.57; 95% CI, 2.19-3.02), and ischemic stroke (HR, 2.15; 95% CI, 1.85-2.51). The adverse diabetes-mortality associations were more evident among women (HR, 2.09; 95% CI, 1.89-2.32) than among men (HR, 1.74; 95% CI, 1.62-1.88) (P for interaction < .001) and more evident among adults aged 30 to 49 years (HR, 2.43; 95% CI, 2.08-2.84) than among adults aged 70 years and older (HR, 1.51; 95% CI, 1.40-1.62) (P for interaction < .001). A similar pattern of association was found between diabetes and cause-specific mortality, with significant variations noted by sex and age. This study found that diabetes was associated with increased risk of death from several diseases among Asian populations. Development and implementation of diabetes management programs are urgently needed to reduce the burden of diabetes in Asia.

ALBI Score as a Predictor of Survival in Patients with Compensated Cirrhosis Resected for Hepatocellular Carcinoma: Exploratory Evaluation in Relationship to PALBI and MELD Liver Function Scores

SUMMARY – The aim of the study was to explore predictive value of the ALBI, PALBI and MELD scores on survival in patients resected for hepatocellular carcinoma with compensated liver cirrhosis and no macrovascular infiltration. In this retrospective study, longitudinal survival analysis was performed. We analyzed patient/tumor characteristics and MELD, ALBI and PALBI scores as liver function tests for predicting survival outcome. Survival was analyzed from the date of liver resection until death, liver transplantation, or end of follow-up. Patients were stratified for age, cirrhosis etiology, presence of esophageal varices, hepatocellular carcinoma stage, microvascular invasion, histologic differentiation, and resection margins. We identified 38 patients (alcoholic cirrhosis in 84.2% of patients) resected over an 8-year period. Median preoperative MELD score was 8, ALBI score -2.63, and PALBI score -2.38. During the follow-up period, 24 patients died. Estimated median survival time was 36 months. Microvascular invasion was observed in 33 patients. Higher ALBI score was associated with 23.1% higher relative risk of death. PALBI score was associated with 12.1% higher relative risk of death, whereas MELD score was not associated with the risk of death. In conclusion, ALBI score demonstrated significant predictive capabilities for survival in patients with compensated cirrhosis resected for hepatocellular carcinoma.