Socioeconomic differences in overall survival from childhood cancer have been shown previously, but the underlying mechanisms remain unclear. We aimed to investigate if social inequalities were seen ...already for early mortality in settings with universal healthcare. From national registers, all children diagnosed with cancer at ages 0-19 years, during 1991-2014, in Sweden and Denmark, were identified, and information on parental social characteristics was collected. We estimated odds ratios (OR) and 95% confidence intervals (CI) of early mortality (death within 90 days after cancer diagnosis) by parental education, income, employment, cohabitation, and country of birth using logistic regression. For children with acute lymphoblastic leukaemia (ALL), clinical characteristics were obtained. Among 13,926 included children, 355 (2.5%) died within 90 days after diagnosis. Indications of higher early mortality were seen among the disadvantaged groups, with the most pronounced associations observed for maternal education (OR
1.65 95% CI 1.22-2.23) and income (OR
1.77 1.25-2.49). We found attenuated or null associations between social characteristics and later mortality (deaths occurring 1-5 years after cancer diagnosis). In children with ALL, the associations between social factors and early mortality remained unchanged when adjusting for potential mediation by clinical characteristics. In conclusion, this population-based cohort study indicated differences in early mortality after childhood cancer by social background, also in countries with universal healthcare. Social differences occurring this early in the disease course requires further investigation, also regarding the timing of diagnosis.
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The impact of the most recent advances, including targeted therapies and immune checkpoint inhibitors, on early (3-month) mortality in lung cancer is unknown. The aims of this study were to evaluate ...the real-world rate of and risk factors for early mortality, as well as trends in early mortality over the last 20 years.
The KBP prospective observational multicenter studies have been conducted every 10 years since 2000. These studies collect data on all newly diagnosed patients with lung cancer (all stages and histologies) over 1 year in non-academic public hospital pulmonology or oncology units in France. In this study, we analyzed data on patient and tumor characteristics from participants in the KBP-2020 cohort and compared the characteristics of patients who died within 3 months of diagnosis with those of all other patients within the cohort. We also carried out a comparative analysis with the KBP-2000 and KBP-2010 cohorts.
Overall, 8999 patients from 82 centers were included in the KBP-2020 cohort. Three-month survival data were available for 8827 patients, of whom 1792 (20.3%) had died. Risk factors for early mortality were: male sex, age >70 years, symptomatic disease at diagnosis, ever smoker, weight loss >10 kg, poor Eastern Cooperative Oncology Group performance status (≥1), large-cell carcinoma or not otherwise specified, and stage ≥IIIC disease. The overall 3-month mortality rate was found to have decreased significantly over the last 20 years, from 24.7% in KBP-2000 to 23.4% in KBP-2010 and 20.3% in KBP-2020 (P < 0.0001).
Early mortality among patients with lung cancer has significantly decreased over the last 20 years which may reflect recent improvements in treatments. However, early mortality remained extremely high in 2020, particularly when viewed in light of improvements in longer-term survival. Delays in lung cancer diagnosis and management could contribute to this finding.
•Of 8827 patients with lung cancer included in the KBP-2020 study, 1792 (20.3%) were dead at 3 months after diagnosis.•Early mortality in LC patients has decreased significantly over the last 20 years but remained extremely high in 2020.•Risk factors for 3-month mortality were similar to those reported in other studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Generally, lactate levels > 2 mmol/L represent hyperlactatemia, whereas lactic acidosis is often defined as lactate > 4 mmol/L. Although hyperlactatemia is common finding in liver transplant (LT) ...candidates, association between lactate and organ failures with Acute-on-chronic Liver Failure (ACLF) is poorly studied. We searched the important variables for pre-LT hyperlactatemia and examined the impact of preoperative hyperlactatemia on early mortality after LT.
A total of 2,002 patients from LT registry between January 2008 and February 2019 were analyzed. Six organ failures (liver, kidney, brain, coagulation, circulation, and lung) were defined by criteria of EASL-CLIF ACLF Consortium. Variable importance of preoperative hyperlactatemia was examined by machine learning using random survival forest (RSF). Kaplan-Meier Survival curve analysis was performed to assess 90-day mortality.
Median lactate level was 1.9 mmol/L (interquartile range: 1.4, 2.4 mmol/L) and 107 (5.3%) patients showed > 4.0 mmol/L. RSF analysis revealed that the four most important variables for hyperlactatemia were MELD score, circulatory failure, hemoglobin, and respiratory failure. The 30-day and 90-day mortality rates were 2.7% and 5.1%, whereas patients with lactate > 4.0 mmol/L showed increased rate of 15.0% and 19.6%, respectively.
About 50% and 5% of LT candidates showed pre-LT hyperlactatemia of > 2.0 mmol/L and > 4.0 mmol/L, respectively. Pre-LT lactate > 4.0 mmol/L was associated with increased early post-LT mortality. Our results suggest that future study of correcting modifiable risk factors may play a role in preventing hyperlactatemia and lowering early mortality after LT.
Background
Prediction of early mortality after hepatectomies for hepatocellular carcinoma is essential to identify high‐risk patients and to decrease the operative mortality rate. Several ...post‐operative clinical risk scores were developed recently to predict mortality post‐hepatectomy; however, which one is the best remains undefined. Therefore, the aim of this study was to evaluate the performance of the different post‐operative clinical risk scores in predicting early mortality after hepatectomies.
Methods
A total of 240 patients who underwent liver resection for hepatocellular carcinoma at our hospital between June 2011 and July 2016 were retrospectively reviewed. Post‐operative clinical risk scores including 50–50 criteria, peak bilirubin >7 mg/dL, model for end‐stage liver disease (MELD), risk assessment for early mortality and Hyder scores were evaluated for their performance in predicting early mortality after hepatic resection using the receiver operating characteristic (ROC) curve.
Results
The 90‐day mortality rate after hepatic resection was around 2.5%. The 50–50 criteria and peak bilirubin >7 mg/dL were weak predictors of early mortality with low sensitivity (area under the ROC curve: 0.65, 0.66, respectively), whereas, Hyder, risk assessment for early mortality, and post‐operative MELD were good predictors of early mortality (area under the ROC curve: 0.89, 0.91 and 0.88, respectively). Moreover, MELD score on post‐operative day 3 was an independent risk factor for 90‐day mortality with an odds ratio of 1.4 (95% confidence interval 1.06–1.81, P = 0.02).
Conclusions
Post‐operative clinical risk scores, especially MELD, were capable of predicting early mortality after liver resection and should be used to identify high‐risk patients and provide them with more intensive medical care.
Prediction of early mortality after hepatectomies for hepatocellular carcinoma is essential to identify high‐risk patients and to decrease the operative mortality rate. Several post‐operative clinical risk scores were developed recently to predict mortality post‐hepatectomy, however, which one is the best remains undefined. Therefore, the aim of this study was to evaluate the performance of the different post‐operative clinical risk scores in predicting early mortality after hepatectomies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective:
Metastatic colon cancer (mCC) poses a great threat to the survival of patients suffering from it. In the past decade, many clinical trials have been carried out to improve the prognosis of ...patients with mCC. Numerous treatments have emerged, and satisfactory efficacy has been demonstrated in randomized phase III trials in highly selective patients with mCC. Our present study aims to investigate whether these therapeutic advances can be reflected to the broader mCC patients who performed cytoreductive colectomy.
Method:
General and prognostic data for patients diagnosed with mCC who underwent cytoreductive colectomy between 2004–2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards model. The hazard ratio (HR) and its 95% confidence interval (CI) were used to evaluate the influence of risk factors on prognosis.
Results:
A total of 26,301 patients diagnosed with mCC treated with cytoreductive colectomy were included in this study. The median overall survival was 19 months (range, 17–23). The good prognosis was associated with patients diagnosed at the most recent year, younger age, non-black race, female, married, without previous history of malignancy, no second malignancy onset, descending/sigmoid/splenic flexure colon tumor, normal CEA levels at diagnosis, low primary tumor burden, T1/T2 stage, N0 stage, single organ metastasis, underwent surgical resection of synchronous distant metastatic lymph nodes or organs, a high number of lymph-node examinations, low positive lymph-node ratio and received adjuvant chemotherapy. The proportion of patients surviving for ≥24 months increased from 37% in 2004 to 44.2% in 2016 (
p
< 0.001), especially in ≤49 years patients 46.8% in 2004 to 57.8% in 2016 (
p
< 0.001). The percentage of patients who died within 3 months decreased between 2004 and 2018 (from 19.6% to 15.7%;
p
< 0.001).
Conclusion:
Over a span of 15 years, the long-term survival has improved in real-world mCC patients who were treated with cytoreductive colectomy, especially among younger patients. However, the median overall survival remains not substantial.
Aim
Indole is a signaling molecule secreted by over 85 species of bacteria, including several Vibrio species, and it has been reported to affect different bacterial phenotypes such as biofilm ...formation, motility, and virulence. In this study, we aimed at investigating the inter‐strain variability of the effect of indole in 12 different strains belonging to the Harveyi clade of vibrios.
Methods and Results
Indole reduced the virulence of all strains towards gnotobiotic brine shrimp larvae. The survival rate of brine shrimp larvae challenged with vibrios pretreated with indole was increased by 1.3‐fold to 1.8‐fold. Additionally, indole significantly decreased the biofilm formation in all of the strains, decreased the swimming motility in eight of the strains, and decreased swarming motility in five of the strains. When cultured in the presence of exogenous indole, the mRNA level of the pirA and pirB toxin genes were down‐regulated to 65% and 46%, and to 62% and 55% in the AHPND‐causing strains Vibrio parahaemolyticus M0904 and Vibrio campbellii S01, respectively.
Conclusions
These data indicate that indole has a significant impact on the virulence of different strains belonging to the Harveyi clade of vibrios.
Significance and Impact of the Study
Our results suggest that indole signaling is a valid target for the development of novel therapeutics in order to control infections caused by Harveyi clade vibrios in aquaculture.
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The presence of 2 or more high-risk cytogenetic abnormalities on FISH characterizes patients as Double/Triple Hit Myeloma (DH/THM). This entity has poorer outcomes, though data from the real-world ...setting is scarce.
We retrospectively analyzed all MM patients presenting to our hospital over 3 years to study the clinical characteristics and outcomes with DH/THM.
Fifty-five (19.2%) of 285 newly-diagnosed MM patients had DH/THM. The most common cytogenetic abnormality was increased copies of chromosome 1q (53 patients, 96.4%)- 22 patients had 3 copies, and 31 patients had 4 or more copies. The most common cytogenetic combination was IgH-FGFR3 translocation, increasing 1q copy number (28 patients; 50.9%). The disease was characterized by aggressive presentation, with 9 patients (16.4%) dying in the first month after diagnosis, and 7 patients (12.7%) dying in the second month. Only 22 patients (40%) achieved a VGPR or better with therapy. The Median EFS and OS for the cohort were 8 months and thirteen months, respectively. On multi-variate analysis, renal failure and plasma cell leukemia were associated with increased mortality risk, while achievement of VGPR or better was associated with better survival.
Our findings suggest that multiple myeloma patients with double/triple hit cytogenetics on FISH have aggressive presentations, high early mortality, and poor outcomes. These patients may benefit from more aggressive regimens and better supportive care.
Double-Hit and Triple-Hit cytogenetics in Multiple Myeloma is associated with poor outcomes; however, real-world data is scarce. Our study highlights the aggressive presentation and dismal prognosis of this subgroup of patients in a real-world setting, confirming its “ultra-high-risk” behavior.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
Background
Acute myeloid leukemia (AML) with rearrangement of lysine methyltransferase 2a gene (KMT2Ar) is characterized by chemotherapy resistance and high rates of relapse. However, additional ...causes of treatment failure or early mortality have not been well‐defined in this entity.
Methods
In a retrospective analysis, causes and rates of early mortality following induction treatment were compared between a cohort of adults with KMT2Ar AML (N = 172) and an age‐matched cohort of patients with normal karyotype AML (N = 522).
Results
The 60‐day mortality in patients with KMT2Ar AML was 15% compared with 7% with normal karyotype (p = .04). We found a significantly higher occurrence of major bleeding events (p = .005) and total bleeding events (p = .001) in KMT2Ar AML compared with diploid AML. Among evaluable patients with KMT2Ar AML, 93% exhibited overt disseminated intravascular coagulopathy compared with 54% of patients with a normal karyotype before death (p = .03). In a multivariate analysis, KMT2Ar and a monocytic phenotypic were the only independent predictors of any bleeding event in patients who died within 60 days (odds ratio, 3.5; 95% CI, 1.4–10.4; p = .03; odds ratio, 3.2; 95% CI, 1–1‐9.4; p = .04, respectively).
Conclusion
In conclusion, early recognition and aggressive management of disseminated intravascular coagulopathy and coagulopathy are important considerations that could mitigate the risk of death during induction treatment in KMT2Ar AML.
Plain Language Summary
Acute myeloid leukemia (AML) with rearrangement of KMT2A is characterized by chemotherapy resistance and high rates of relapse. However, additional causes of treatment failure or early mortality have not been well‐defined in this entity.
In this article, that KMT2A‐rearranged AML is demonstrably associated with higher early mortality and an increased risk of bleeding and coagulopathy, specifically, disseminated intravascular coagulation, compared with normal karyotype AML.
These findings emphasize the importance of monitoring and mitigating coagulopathy in KMT2A‐rearranged leukemia similar to what is done in acute promyelocytic leukemia.
KMT2Ar acute myeloid leukemia (AML) is associated with increased major and minor bleeding events, disseminated intravascular coagulopathy (DIC), and early mortality. Early recognition and aggressive management of DIC and coagulopathy could mitigate the risk of death during induction therapy in KMT2Ar AML.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Our previous work on the mechanism of virulence for the unique isolates of Vibrio parahaemolyticus that cause acute hepatopancreatic necrosis disease (VPAHPND) revealed that it was mediated by a ...binary Pir-like toxin pair ToxA and ToxB. These toxins are located on the pVA plasmid, a plasmid carried by AHPND-causing strain of V. parahaemolyticus with a size of approximately 69kbp. Using the coding sequences of ToxA, a one-step PCR detection method for VPAHPND was introduced in June 2014 but had the limitation that attempts to adapt it into a nested PCR protocol were unsuccessful. As a result, low levels of VPAHPND in shrimp or other samples could not be detected without first preparing an enrichment broth culture to allow bacterial growth before extraction of template DNA. Here, we describe the AP4 (abbreviation of AHPND detection version 4) method, a two-tube nested PCR method that targets the tandem genes ToxA and ToxB, including the 12bp spacer that separates them on pVA plasmid. Testing of the method revealed that it gave 100% positive and negative predictive values for VPAHPND using a panel of 104 bacterial isolates including 51 VPAHPND isolates and 53 non-AHPND isolates, the latter including 34 isolates of V. parahaemolyticus and 19 isolates of other bacteria found in shrimp ponds, including other Vibrio species. The AP4 nested PCR method was 100 times more sensitive (100fg total DNA template) than the one-step AP3 (10pg total DNA template) method, and it could detect VPAHPND in experimentally challenged shrimp by 6h post immersion (n=2/3), while AP3 could not detect is until 12h post immersion (n=1/3). Thus, the AP4 method may be useful in detecting VPAHPND isolates in samples where target material is limited (e.g., small tissue quantity or archived DNA) and enrichment cannot be employed (i.e., frozen samples or samples preserved in alcohol).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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