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, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Early mortality syndrome (EMS) refers to acute mortality within approximately 35 days of shrimp culture. It is often equated with acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio ...isolates that produce Pir-like toxins. To better understand EMS, 200 Thai shrimp ponds were randomly selected prior to stocking and subsequently sampled from 19/08/2013 to 23/04/2014 to determine the pond prevalence of various pathologies, and particularly those targeting the shrimp hepatopancreas (HP). Ponds exhibiting acute mortality within 35 days were labeled EMS ponds while others were labeled non-EMS ponds. Shrimp samples from each pond (10) were subjected to histological analysis focused on hepatopancreatic (HP) lesions. Similar samples (10) were tested by PCR for the microsporidian Enterocytozoon hepatopenaei (EHP), white spot syndrome virus (WSSV), yellow head virus (YHV) and Vibrio that cause AHPND. Preservation failed for 4 ponds. Results from the 196 ponds remaining were divided, into 4 groups based largely on HP histology: (1) ponds positive for AHPND by histology and/or PCR at 20.9% prevalence (41/196); (2) ponds showing HP bacterial lesions at 14.8% prevalence (29/196); (3) ponds showing collapsed HP tubule epithelia at 25.0% prevalence (49/196); and (4) ponds showing no HP pathology (normal HP) at 39.3% prevalence (77/196) ponds. The overall prevalence of EMS ponds (i.e., mortality ≤35 days) was 16.3% (32/196), but only 18/32 (56.3%) of these fell within AHPND Group 1. The other 14 EMS ponds (43.7%) were divided among the remaining three groups: Group 2 with HP bacterial lesions (3/32 = 9.4%), Group 3 with collapsed HP tubule epithelia (1/32 = 3.1%) and Group 4 with normal HP histology (a surprising 10/32 = 31.2%). Across all groups, prevalence of ponds exhibiting aggregated transformed microvilli (ATM) was high at 79.8%, as was prevalence of EHP at 60.7%. The overall prevalence of WSSV was low at 4.1% (8/196), while YHV was not found. Overall, the results indicated that equating EMS with AHPND without confirmatory analysis could lead to overestimation of its impact on shrimp aquaculture and to failure in recognizing other important causes of early mortality.
•Determination of shrimp pathogens and pathologies were carried out in the 200 pre-selected Thai shrimp ponds.•Among 196 ponds examined, 32 ponds were reported to be EMS ponds.•Only 18 in 32 EMS ponds were found to be positive for AHPND by histology and/or PCR.•Shrimp EMS is not equal to AHPND.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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, SBCE, SBMB, UL, UM, UPUK
Purpose
To analyse a wide set of routine laboratory parameters at admission to predict mortality within 30 post-operative days in elderly patients with hip fracture, as well as calculate the critical ...values of those biomarkers.
Method
Data of 994 patients older than 65 years with hip fracture were analysed of which 89 (8.2%) died within 30 post-operative days. Variables described in the literature with potential influence on early mortality were collected, including demographics, fracture type, American Society of Anesthesiologists score, Charlson’s comorbidity index and pre-operative Hodkinson’s mental test and the Katz index for activities of daily living. In addition, an exhaustive collection of biomarkers from routine blood testing at admission was performed. Critical levels of biomarkers were calculated by the method of area under ROC curve.
Results
At admission, early mortality group had significantly higher Charlson’s index (
p
= 0.001) and lower the Katz index (
p
= 0.001). The surgical delay also was significantly longer in that group (
p
= 0.001). In univariate analyses, serum concentration at admission of total protein (
p
= 0.004), albumin (
p
= 0.001), sodium (p = 0.001), and parathyroid hormone (PTH) (
p
= 0.001) were significantly different between both groups. In multivariate analysis, serum albumin < 2.9 g/dL (
p
= 0.013), sodium < 127 mEq/L (
p
= 0.035) and PTH > 65 pg/mL (
p
= 0.005) were predictors of early mortality. The three biomarkers together accounted for 67% of the variability in early mortality.
Conclusion
The association of altered levels at admission of serum concentration of albumin, sodium and PTH was predictor of early mortality following hip fracture surgery in elderly patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Thiamine deficiency complex (TDC) is a disorder resulting from the inability to acquire or retain thiamine (vitamin B
1
) and has been documented in organisms in aquatic ecosystems ranging from the ...Baltic Sea to the Laurentian Great Lakes. The biological mechanisms leading to TDC emergence may vary among systems, but in fishes, one common outcome is high mortality among early life stages. Here, we review the causes and consequences of thiamine deficiency in fishes and identify potential solutions. First, we examine the biochemical and physiological roles of thiamine in vertebrates and find that thiamine deficiency consistently results in impaired neurological function across diverse taxa. Next, we review natural producers of thiamine, which include bacteria, fungi, and plants, and suggest that thiamine is not currently limiting for most animal species inhabiting natural aquatic environments. A survey of historic occurrences of thiamine deficiency identifies consumption of a thiamine-degrading enzyme, thiaminase, as the primary explanation for low levels of thiamine in individuals and subsequent onset of TDC. Lastly, we review conservation and management strategies for TDC mitigation ranging from evolutionary rescue to managing for a diverse forage base. As recent evidence suggests occurrences of thiamine deficiency may be increasing in frequency, increased awareness and a better mechanistic understanding of the underlying causes associated with thiamine deficiency may help prevent further population declines.
A quantitative polymerase chain reaction (qPCR) assay was developed, based on a TaqMan probe, to detect and quantify a virulence plasmid harbored by the bacterium Vibrio parahaemolyticus which can ...cause acute hepatopancreatic necrosis disease (AHPND). The assay uses a pair of PCR primers, which amplify a 135-bp DNA fragment, and a TaqMan probe selected from the plasmid pirA-like gene. This qPCR assay reacted with AHPND-pathogenic isolates of V. parahaemolyticus collected from Vietnam and Mexico, but not with non-pathogenic strains of Vibrio spp. For quantification, a plasmid (pVpPirA-1) containing the target pirA-like gene was constructed, purified and serially diluted to be used as a standard. With this standard, the qPCR assay was then used to quantify the virulence plasmid in shrimp samples collected from different farms. Up to 5.8×105 copy per mg tissue were detected in AHPND-affected shrimp collected from Vietnam. Lower quantities, up to 1.5×104 copies per mg of tissues were detected in affected shrimp collected from a Chinese farm. In the laboratory bioassays, similar plasmid quantities, 1.8×103 to 4.7×106 copies of plasmid per mg of tissues were found in the moribund/dead shrimp, 3.5×102 to 2.2×106 copies of plasmid per mL were detected in the water samples. This assay is specific with high sensitivity (10 copies of virulence plasmid) and can be used to detect AHPND-pathogenic V. parahaemolyticus in shrimp and water samples.
•We developed a qPCR method to detect and quantify AHPND (EMS).•This assay is specific with high sensitivity (10 copies of virulence plasmid).•This method can be used for quantification in water and shrimp samples from fields.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) to treat peritoneal surface malignancy (PSM) has gained a positive result compared with palliative ...chemotherapy alone in several cancer types. However, its postoperative care could be challenging. We aimed to develop a predicting model on early mortality.
We retrospectively reviewed 132 PSM patients who had received CRS-HIPEC. The optimal cut-off value of the neutrophil-to-lymphocyte ratio (NLR) was determined as 4.4 by using the receiver operating characteristic curve analysis with an area under the curve (AUC) of 0.75. The impact of NLR on survival was elucidated by comparing the pre-operative low (NLR≤ 4.4, n = 101) and high (NLR> 4.4, n = 31) groups using the Kaplan-Meier method. The significant variables selected in multivariate analysis on early mortality were used in prediction model development.
Multivariate analysis showed that incomplete CRS, major postoperative complications, higher pre-operative NLR, and dynamic NLR changes were significant predictors of early mortality. Our perioperative prediction of prognosis (triple P) model contained four independent risks, and the AUC after classification was 0.860 (95% confidence interval CI: 0.773–0.947). External validation confirmed positive discrimination ability (AUC: 0.808, 95% CI: 0.666–0.950).
In conclusion, our triple P model provides great determination in outcomes prediction and it is easily obtained, reliable, and applicable in routine practice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
Immune checkpoint inhibitors (ICI) are a promising treatment, but may cause hyperprogressive disease and early death. The present study investigated early mortality factors in ICI monotherapy ...for lung cancer.
Patients and methods
We retrospectively reviewed all patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) and treated with ICI monotherapy (nivolumab, pembrolizumab, and atezolizumab) between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Early death was defined as patients who died within 60 days of ICI treatment.
Results
A total of 166 patients were included. The majority of patients (87%) had an Eastern cooperative oncology group (ECOG) Performance status (PS) of 0/1. There were 21 early deaths. Significant differences were observed in ECOG PS, the histological type, liver metastasis, tumor size, the white blood cell count, neutrophils (%), lymphocytes (%), the neutrophil-to-lymphocyte ratio in serum (sNLR), C-reactive protein (CRP), and albumin between the groups with or without early death. Univariate logistic regression analyses identified ECOG PS score ≥ 2, liver metastasis, tumor size ≥ 5 cm, neutrophils ≥ 69%, lymphocytes < 22%, sNLR ≥ 4, CRP ≥ 1 mg/dl, and albumin < 3.58 g/dl as significant risk factors for early death. A multivariate logistic regression analysis revealed that liver metastasis (Odds ratio OR, 10.3;
p
= 0.008), ECOG PS score ≥ 2 (OR, 8.0;
p
= 0.007), and a smoking history (OR, 0.1;
p
= 0.03) were significant risk factors for early death.
Conclusion
Liver metastases, ECOG PS score ≥ 2, and a non-smoking history are early mortality factors in ICI monotherapy for advanced or metastatic NSCLC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Acute hepatopancreatic necrosis disease (AHPND, also known as early mortality syndrome, EMS) caused by Vibrio parahaemolyticus has resulted in severe marine shrimp mortality and significant economic ...losses in related aquaculture throughout Southeast Asia and Central America. As no viable remedy has yet been reported, the main objective of this study was to develop an effective bacteriophage (phage)-based method of controlling AHPND/EMS. To determine the bacteriolytic activity of phage pVp-1 against V. parahaemolyticus strains causing AHPND/EMS, its infectivity was tested on 22 strains isolated from geographically diverse regions (5 of the Asian type and 17 of the Mexican type). This phage was able to infect 90.9% (20 strains among 22 strains) of the AHPND/EMS-related V. parahaemolyticus strains used in this study, and demonstrated substantial bacteriolytic activity against three strains known to be highly pathogenic. To the best of our knowledge, this is the first report of a virulent phage infecting V. parahaemolyticus strains responsible for AHPND/EMS, and indicates the potential utility of pVp-1 in phage therapy.
•Vibrio parahaemolyticus causes Acute hepatopancreatic necrosis disease (AHPND) in shrimp.•Bacteriophage pVp-1 infected 90% of V. parahaemolyticus strains tested.•pVp-1 showed high bacteriolytic activity against AHPND-associated V. parahaemolyticus.•First report of bacteriophage infecting AHPND, offering its potential as alternatives to antibiotics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Post-myocardial infarction ventricular septal rupture (VSR) is a rare and severe complication of myocardial infarction. To find early mortality (<30 days) risk factors of device VSR closure and to ...evaluate its medium-term outcome.
Multicenter retrospective analysis on all 46 consecutive patients with percutaneous (n = 43) or hybrid (n = 3) VSR closure in 2000–2020 with various nitinol wire mesh occluders. Medical records, hemodynamic data, procedure results, short- and mid-term follow-up were analyzed (4.8 ± 3.7 years, range: 0.1–15, available in 61.7% of patients). Of the patients, 34.8% underwent VSR closure in acute phase (<21 days after VSR occurrence), 17.4% underwent device closure due to significant residual shunt after previous VSR surgery.
Success rate was 78.3%. More than moderate residual shunt, major complications, and early surgical reintervention affected 18.9%, 15.2% (including 2 intra-procedural deaths), and 21.7% of patients, respectively. Early mortality was 26.1% (13.9% in successful vs. 70% in unsuccessful closure; p < 0.001). Older age, need for intra-aortic balloon counterpulsation, severe complications, and procedural failure were identified as risk factors for early mortality. Among patients who survived the early period, the 5-year survival rate was 57.1%. NYHA class improved in 88.2% patients at the latest follow-up.
Procedure of VSR device closure demonstrates an acceptable technical success rate; however, the incidence of severe complications and early mortality is notably high. Older patients in poor hemodynamic condition and those with unsuccessful occluder deployment are particularly at a higher risk of a fatal outcome. The prognosis after early survival is promising.
•The outcomes of percutaneous or hybrid device closure for post-myocardial infarction ventricular septal rupture are limited, and their significance remains uncertain. We conducted an analysis involving 46 patients, revealing that older age, the necessity for intra-aortic balloon counterpulsation, severe complications, and procedural failure constitute risk factors for early mortality. Post-infarct muscular ventricular septal defect (VSD) occluders are more commonly employed during the acute phase of rupture healing, while atrial septal occluders are preferentially utilized in the chronic phase. Although this approach yields an acceptable technical success rate, the incidence of severe complications and early mortality is notably elevated. The outcome after early survival is promising.
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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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