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, SAZU, SBCE, SBMB, UL, UM, UPUK
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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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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, ZRSKP
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.
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
Background
Despite the increased availability and use of novel therapies for multiple myeloma, early mortality is a pervasive challenge with a significant impact on older adults. Reported rates and ...predictors of early mortality have varied in the literature, with most studies seldom focusing on community‐treated patients.
Methods
In this retrospective cohort analysis of a real‐world electronic health record–derived deidentified database of 7512 patients newly diagnosed with multiple myeloma between January 1, 2011, and February 2, 2021, and treated primarily in US‐based community oncology practices, factors associated with early mortality (defined as death within 6 months after the multiple myeloma diagnosis) were examined with the use of binary logistic regression.
Results
The median age was 70 years overall. We found an overall early mortality rate of 8.3%, with 73% of early deaths occurring in those aged ≥70 years. Among the early deaths, only 49 patients (8.7%) had documented disease progression before death (median time to progression, 30 days interquartile range, 7–53 days). Baseline factors associated with higher odds of early mortality included an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, Revised International Staging System (R‐ISS) stage III, an age ≥ 70 years, receipt of proteasome inhibitor–doublet therapy, a light‐chain isotype, and the presence of renal dysfunction (estimated glomerular filtration rate < 30 mL/min). Among those aged ≥70 years, ECOG PS ≥ 2 and R‐ISS stage III remained the strongest predictors of early mortality.
Conclusions
Early mortality disproportionately affects older adults (aged ≥70 years) with multiple myeloma. Interventions to support this population are needed to reduce disparate survival outcomes.
Plain language summary
Factors associated with an increased risk of dying within 6 months (early mortality) of a new diagnosis of multiple myeloma (MM) among 7512 mostly community‐treated patients with MM were evaluated.
The early mortality rate was 8.3%; among those deaths, 49 patients (8.7%) had documented evidence of MM progression before death.
The risk of early mortality was greatest for older patients (aged ≥70 years) and those with a poor performance status, poor kidney function, a higher disease stage, and light‐chain MM and those receiving two‐drug MM therapies.
These findings highlight the need for supportive interventions geared toward older adults with MM.
Approximately 9% of adults newly diagnosed with multiple myeloma will die within 6 months. Most early deaths occur in those aged 70 years or older and among those with advanced disease, a poor performance status, and kidney dysfunction and those who have received a proteasome inhibitor‐based doublet regimen.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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, SAZU, SBCE, SBMB, UL, UM, UPUK
Toxins PirvpA and PirvpB were first described in 2014 from Vibrio parahaemolyticus (VP) isolates discovered in 2013 as the cause of acute hepatopancreatic necrosis disease (AHPND) that emerged as a ...new disease of Chinese cultivated shrimp in 2009. It was subsequently reported from Thailand in 2012. By using PirvpA and PirvpB specific monoclonal antibodies (MAbs) together with reference VPAHPND isolates to screen archived bacterial cultures, we discovered 3 isolates of Vibrio (previously identified as V. harveyi) including VH 639, VH 1526 and VH Surat that were positive for both PirA and PirB toxins, even though the isolates were collected in Thailand over 10 years prior to reported Thai AHPND outbreaks. Western blot analysis revealed that the PirA/B toxins from these Vibrio isolates matched the molecular masses of the PirvpA/B toxins of previously described VPAHPND isolates. PCR analysis using VPAHPND detection methods that target the PirvpA and PirvpB toxin genes (AP4 and TUMSAT-Vp3) gave amplicons of the expected size from the 3 Vibrio isolates, and sequence analysis of the amplicons revealed 99% identity with the sequences of the PirvpA and PirvpB genes of previously described VPAHPND isolates. Pathogenicity tests performed by reverse gavage and immersion challenge tests demonstrated the pattern of AHPND pathology. Species confirmation of these 3 Vibrio isolates by multilocus sequence analysis (MLSA) of 16S rRNA, rpoD, rctB, and toxR genes revealed that they belong to V. campbellii clade. The results revealed that V. campbellii isolates capable of producing PirA and PirB toxins were present in Thailand up to 7 years before AHPND was reported from China and up to a decade before it was reported from Thailand. The plasmid or chromosomal location of the PirA and PirB toxin genes in these archived V. campbellii isolates and their phylogenetic relationship to current VPAHPND isolates are being determined.
•Three archived isolates of V. campbellii were positive for PirvpA and PirvpB toxins by using specific monoclonal antibodies.•Those three virulent isolates were collected in Thailand 5–10 years prior to reported Thai AHPND outbreaks.•The PirvpA and PirvpB toxin genes from V. campbellii shared 99% identity with that of previously described VPAHPND isolates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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