Over the past two decades, there have been significant advances in the treatment of multiple myeloma that have led to an improvement in overall survival (OS). However, a notable proportion of ...patients continue to experience early mortality (EM). This raises the possibility that the overall improvement in myeloma survival has not extended equally to all groups. Using the latest data drawn from the Surveillance Epidemiology and End Results (SEER) database of patients in the United States spanning 2000-2019, we explored EM and OS in the context of various important sociodemographic factors, such as race-ethnicity. Through regression modeling, we demonstrated that those living outside the northeast, of older age, male gender, and those of certain racial and ethnic minority status (non-Hispanic Blacks and Hispanics) had higher EM and worse OS. Additionally, we showed that some of these factors, such as race and to a degree socioeconomic status, did not contribute to worse survival after the two-year mark. Finally, to better understand EM trends in the context of new developments in care and therapeutics over the last 20 years, we looked at 2-year OS and relative survival rate over 2000-2017 in select sociodemographic factors and noted consistent improvement in EM as well. Through these various analyses, we see that EM has improved over the past 20 years with new therapeutic developments, but certain specific groups remain at risk that could benefit from more targeted approaches at the therapeutic and possibly population level.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Acute hepatopancreatic necrosis disease (AHPND) first emerged as a new shrimp disease in 2009 that heavily affected shrimp industry leading to global economic losses. The etiological agent was ...previously identified as Vibrio parahaemolyticus that carries a plasmid containing toxins (PirA and PirB). However, recent researches revealed that V. parahaemolyticus is not the only bacterial species capable of causing AHPND, thus this study screened on bacterial strains with AHPND toxins from Penaeus vannamei shrimps in Malaysia. Out of the 86 isolated total strains, 12 AHPND positive strains were arbitrarily selected and were evaluated in in vivo assay using Artemia franciscana as a model organism. All the 12 AHPND positive strains with PirA and PirB genes demonstrated significant mortalities (P < 0.05) of A. franciscana compared to the negative control. The 12 AHPND positive strains were identified using molecular methods of 16S rRNA, RctB and RpoD region amplifications belonged to the Harveyi clade and were closely related to V. parahaemolyticus and Vibrio harveyi. Further test showed that the yellow colony V. harveyi strain BpShHep24 was found to be more virulent than the green colony V. parahaemolyticus strain BpShHep31 in shrimp P. vannamei challenge test. Histological examination of shrimp hepatopancreas challenged with yellow colony V. harveyi strain BpShHep24 showed massive sloughing of hepatopancreas tubules of epithelial cells into the lumen, haemocyte infiltrations, proximal-to-distal lesion of hepatopancreas and collapsed tubule epithelia within 24 h.
•Identification of Vibrio harveyi and V. parahaemolyticus causing AHPND with PirA and PirB genes in Malaysia.•16S rRNA solely is insufficient to identify Vibrio.•Multilcous sequencing analysis (MLSA) is a reliable tool for accurate identification of Vibrio species.•Yellow V. harveyi strain BpShHep24 is more virulent to whiteleg shrimp than green V. parahaemolyticus strain BpShHep31.•Farmers should not rely on colony colors on thiosulphate-citrate salt sucrose (TCBS) agar.
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The early crossing of survival curves in randomised clinical trials (RCTs) with immune checkpoint blockers suggests an excess of mortality in the first months of treatment. However, the exact ...estimation of the early death (ED) rate, the comparison between ED upon immune checkpoint inhibitors (ICI) alone or in combination with other agents and the impact of tumour type, and PD-L1 expression on ED are unknown.
RCTs comparing ICI alone (ICI-only group) or in combination with other non-ICI therapies (ICI-OT group) (experimental arms) versus non-ICI treatments (control arm) were included. ED was defined as death within the first 3 months of treatment. The primary outcome was the comparison of ED between experimental and control arms, and the secondary outcome was the comparison of ED risk between ICI-only and ICI-OT. ED rates estimated by risk ratio (RR) were pooled by random effect model.
A total of 56 RCTs (40,215 participants, 14 cancer types) were included. ED occurred in 14.2% and 6.7% of patients in ICI-only and ICI-OT groups, respectively. ED risk significantly increased with ICI-only (RR: 1.29, 95% CI 1.05–1.57) versus non-ICI therapies, while it was lower with ICI-OT versus non-ICI treatments (RR: 0.81, 95% CI 0.73–0.90). ED risk was significantly higher upon ICI-only compared to ICI-OT (RR: 1.57, 95% CI 1.26–1.95). Gastric and urothelial carcinoma were at higher risk of ED. PD-L1 expression and ICI drug classes were not associated with ED.
ED upon first-line ICI is a clinically relevant phenomenon across solid malignancies, not predictable by PD-L1 expression but preventable through the addition of other treatments to ICI.
•This meta-analysis quantifies excess of early mortality upon first-line immunotherapy in solid tumors.•Early mortality risk increases with immunotherapy alone versus other treatments.•Neither PD-L1 levels nor class of immune checkpoint inhibitors predict early mortality.•Gastric and urothelial carcinoma are at higher risk of early mortality upon immunotherapy.•Immunotherapy combination strategies can prevent early mortality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
It remains unclear today whether risk scores created specifically to predict early mortality after cardiac operations for infective endocarditis (IE) outperform or not the European System for Cardiac ...Operative Risk Evaluation II (EuroSCORE II).BACKGROUNDIt remains unclear today whether risk scores created specifically to predict early mortality after cardiac operations for infective endocarditis (IE) outperform or not the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II).Perioperative data and outcomes from a European multicenter series of patients undergoing surgery for definite IE were retrospectively reviewed. Only the cases with known pathogen and without missing values for all considered variables were retained for analyses. A comparative validation of EuroSCORE II and five specific risk scores for early mortality after surgery for IE - (1) STS-IE (Society of Thoracic Surgeons for IE); (2) PALSUSE (Prosthetic valve, Age ≥70, Large intra-cardiac destruction, Staphylococcus spp, Urgent surgery, Sex (female), EuroSCORE ≥10); (3) ANCLA (Anemia, New York Heart Association class IV, Critical state, Large intra-cardiac destruction, surgery on thoracic Aorta); (4) AEPEI II (Association pour l'Étude et la Prévention de l'Endocardite Infectieuse II); (5) APORTEI (Análisis de los factores PROnósticos en el Tratamiento quirúrgico de la Endocarditis Infecciosa) - was carried out using calibration plot and receiver-operating characteristic curve analysis. Areas under the curve (AUCs) were compared 1:1 according to the Hanley-McNeil's method. The agreement between APORTEI score and EuroSCORE II of the 30-day mortality prediction after surgery was also appraised.METHODSPerioperative data and outcomes from a European multicenter series of patients undergoing surgery for definite IE were retrospectively reviewed. Only the cases with known pathogen and without missing values for all considered variables were retained for analyses. A comparative validation of EuroSCORE II and five specific risk scores for early mortality after surgery for IE - (1) STS-IE (Society of Thoracic Surgeons for IE); (2) PALSUSE (Prosthetic valve, Age ≥70, Large intra-cardiac destruction, Staphylococcus spp, Urgent surgery, Sex (female), EuroSCORE ≥10); (3) ANCLA (Anemia, New York Heart Association class IV, Critical state, Large intra-cardiac destruction, surgery on thoracic Aorta); (4) AEPEI II (Association pour l'Étude et la Prévention de l'Endocardite Infectieuse II); (5) APORTEI (Análisis de los factores PROnósticos en el Tratamiento quirúrgico de la Endocarditis Infecciosa) - was carried out using calibration plot and receiver-operating characteristic curve analysis. Areas under the curve (AUCs) were compared 1:1 according to the Hanley-McNeil's method. The agreement between APORTEI score and EuroSCORE II of the 30-day mortality prediction after surgery was also appraised.A total of 1,012 patients from five European university-affiliated centers underwent 1,036 cardiac operations, with a 30-day mortality after surgery of 9.7%. All IE-specific risk scores considered achieved better results than EuroSCORE II in terms of calibration; AEPEI II and APORTEI score showed the best performances. Despite poor calibration, EuroSCORE II overcame in discrimination every specific risk score (AUC, 0.751 vs. 0.693 or less, p=0.01 or less). For a higher/lesser than 20% expected mortality, the agreement of prediction between APORTEI score and EuroSCORE II was 86%.RESULTSA total of 1,012 patients from five European university-affiliated centers underwent 1,036 cardiac operations, with a 30-day mortality after surgery of 9.7%. All IE-specific risk scores considered achieved better results than EuroSCORE II in terms of calibration; AEPEI II and APORTEI score showed the best performances. Despite poor calibration, EuroSCORE II overcame in discrimination every specific risk score (AUC, 0.751 vs. 0.693 or less, p=0.01 or less). For a higher/lesser than 20% expected mortality, the agreement of prediction between APORTEI score and EuroSCORE II was 86%.EuroSCORE II discrimination for 30-day mortality after surgery for IE was higher than five established IE-specific risk scores. AEPEI II and APORTEI score showed the best results in terms of calibration.CONCLUSIONEuroSCORE II discrimination for 30-day mortality after surgery for IE was higher than five established IE-specific risk scores. AEPEI II and APORTEI score showed the best results in terms of calibration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aquafeeds contain protein ingredients such as fishmeal and soybean meal, yet their production puts pressure on the environment. Finding novel protein sources such as dried microbial biomass produced ...on recovered or renewable resources, so-called single-cell protein or microbial protein, can contribute to a more sustainable aquaculture industry. New microbial protein sources are emerging with photoheterotrophic grown purple non‑sulfur bacteria (PNSB) showing high potential, yet research of PNSB as added-value protein ingredient is limited. This research studied their use as a protein source for the white leg shrimp (Penaeus vannamei) and investigated the shrimp's tolerance against Vibrio and ammonia stress. A 28-day shrimp feeding trial was performed with a commercial formulation without PNSB as experimental control (diet i), two pure PNSB species, namely Rhodopseudomonas palustris (diets ii-iii), Rhodobacter capsulatus (diets iv-v) at two protein inclusion levels of 5 and 11 g PNSBprotein 100 g−1 feedprotein and a PNSB enriched culture at a protein inclusion level of 11 g PNSBprotein 100 g−1 feedprotein (diet vi). For the shrimp fed with Rb. capsulatus, 5–25% higher individual weights (p < .05) and better feed conversion ratios were observed relative to the commercial diet (1.3–1.4 vs. control 1.7 g feed g−1 biomass; p < .05). The diet containing Rps. palustris at 5 g PNSBprotein 100 g−1 feedprotein inclusion also showed higher individual weights (26%, p < .05) and a better feed conversion ratio compared to the commercial feed (1.3 vs. control 1.7 g feed g−1 biomass; p < .05). The challenge test subsequent to the feeding trial showed a higher tolerance against ammonia (3 mg N L−1) for shrimp fed with Rps. palustris (survival 63–75% vs. 8% commercial diet; p < .05). For a post-feeding challenge test with Vibrio parahaemolyticus TW01, mortality rates were equal among all treatments. Yet, in vitro tests in 96-Well plates and agar spot assays showed that the PNSB species (i) Rps. palustris, (ii) Rb. capsulatus, (iii) Rb. sphaeroides, (iv) Rhodospirillum rubrum and (v) Afifella marina suppressed the pathogens V. parahaemolyticus TW01 and V. campbellii LMG 21363. Overall, this study demonstrated the potential of PNSB as an added-value protein ingredient in shrimp nursery feed. This can contribute to a circular economy, as PNSB can be cultivated on recovered or renewable resources (e.g. wastewater).
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•Purple non-sulfur bacteria (PNSB) enhance the growth performance of shrimp.•PNSB-fed shrimp has better feed conversion ratio, growth rate and weight gain.•Shrimp fed with Rhodopseudomonas are more resistant against ammonia stress.•In vitro tests showed that freeze-dried and live PNSB inhibit Vibrio pathogens.
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Two Vibrio parahaemolyticus virulence genes, pirAvp and pirBvp, are known to encode a binary photorhabdus insect-related (Pir) toxin that causes acute hepatopancreatic necrosis disease (AHPND) in ...shrimp. These genes are flanked with repeats of a mobile element (insertion sequence) in a large plasmid. This insertion sequence is closely (92%) related to the known insertion sequence ISVal1. The pirABvp genes and the flanking ISVal1 forms a 5535-bp composite transposon, designated Tn6264. There are pirABvp gene deletions in some strains of V. parahaemolyticus. During 2013–2016, we found 2 types of pirABvp deletion mutants from AHPND-affected farms. The type I mutants included 3 strains with deletions (4.4-kb or 6.0-kb) of entire pirABvp genes and the downstream ISVal1, and these mutants were named pirABvp(‐). The type II mutants included 3 strains with smaller deletions (1.5-kb or 1.6-kb) including a pirAvp gene and a partial pirBvp gene, and were named pirAvp(‐). In laboratory bioassays, these were not pathogenic to shrimp confirming that both pirAvp and pirBvp are required for AHPND pathogenicity. During 2016, we also isolated 4 V. campbellii strains carrying pirABvp genes from diseased shrimp. These V. campbellii stains were found, through laboratory bioassays and histological evaluation, to cause AHPND.
•A composite transposon, named Tn6264, consists of pirABvp genes and the flanking insertion sequence (ISVal1), is associated with AHPND of shrimp.•Two types of pirABvp deletion mutants of V. parahaemolyticus were found in the AHPND-affected farms.•The type I mutants, named pirABvp(-), have deletions (4.4-kb or 6.0-kb) of entire pirABvp genes and the downstream ISVal1.•The type II mutants, named pirAvp(-), have smaller deletions (1.5-kb or 1.6-kb) of pirAvp and including a partial pirBvp.•V. campbellii strains carrying pirABvp genes were found, through laboratory bioassays and histologicial evaluation, to cause AHPND.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objective: A prediction model: "TERMINAL-24,” was developed and internally validated for use in predicting early mortality of multiple trauma patients in the Emergency Department. In this study this ...model's external validity and generalizability was evaluated.Material and Methods: A retrospective cohort was used for the construction of two datasets. Temporal external validation used the dataset from the same location at a different period, and geographic external validation used the dataset from a different location.Results: In total, 1,932 patients underwent temporal external validation, with 14 (0.7%) patients dyeing within 8 hours, 35 (1.8%) patients died between 8 and 24 hours, and 1,883(97.5%) patients were alive at 24 hours. From this, 2,336 patients were eligible for geographical external validation, with 106 (4.5%) patients having died at the emergency room, 143 (6.1%) patients died in hospital and 2,087 (89.3%) patients survived. The TERMINAL-24 score was applied to both datasets, with a benchmark of 4 or higher (range 0-5). In the temporal dataset, this score showed a mortality of greater than 20% (specificity 0.97) area under the receiver operating characteristic curve (AuROC) 0.91 (95% Confidence interval (CI) 0.85-0.96); whereas, it demonstrated a mortality of greater than 60% (specificity 0.99) AuROC 0.92 (95%CI 0.89-0.94) in the geographical dataset.Conclusion: TERMINAL-24 was effective at predicting early death in the emergency room. It was successfully implemented within the same hospital; hoever, the cut-point should be adapted for application in other institutions with unspecified time of death. Prospective studies at different hospitals should be planned to generalize this scoring system for clinical practice.
Several shrimp diseases are new or newly emerged in Asia, including acute hepatopancreatic necrosis disease (AHPND), hepatopancreatic microsporidiosis (HPM), hepatopancreatic haplosporidiosis (HPH), ...aggregated transformed microvilli (ATM) and covert mortality disease (CMD). In addition to these, white spot disease (WSD), yellow head disease (YHD) and infectious myonecrosis (IMN) continue as the most serious viral threats to shrimp farmers in the region. Other diseases such as monodon slow growth syndrome (MSGS), white tail disease (WTD) and abdominal segment deformity disease (ASDD) are of less concern. In contrast, Taura syndrome virus (TSV) and infectious hypodermal and hematopoietic necrosis virus (IHHNV) have become innocuous due to the widespread use of highly tolerant specific pathogen free (SPF) stocks of Penaeus (Litopenaeus) vannamei that dominate production. Similarly, diseases caused by monodon baculovirus (MBV) and hepatopancreatic parvovirus (HPV) appear not to affect P.vannamei. Spread of diseases has been promoted by the use of live or fresh broodstock feeds such as polychaetes and clams. Also, shortages in the supply of imported SPF broodstock led some entrepreneurs to employ post larvae (PL) of imported SPF stocks to produce 2nd generation broodstock in open shrimp ponds where they became contaminated and were then used to produce PL for stocking ponds. These practices left the whole shrimp industry vulnerable to rapid spread of the new and newly emerging diseases and resulted in the current crisis in Asian shrimp culture. The situation has been exacerbated since 2009 by an almost exclusive focus on AHPND, which is only partially responsible for what has been widely called early mortality syndrome (EMS). The purpose of this review is to summarize progress of research on AHPND bacteria and also to encourage a wider focus on additional pathogens that are causing farm losses. The significance of these diseases and their implications for the future of shrimp aquaculture are discussed.
This review summarizes recent information about new and newly emerging diseases of cultured shrimp in Asia and discusses the biosecurity lapses that led to the current shrimp production crisis. All industry stakeholders must be aware of this situation and of the need for regional and global collaborative efforts to stem this crisis and prevent future development of another.
•Diseases have caused the current production crisis in Asian shrimp aquaculture.•Most important is new AHPND caused by unique isolates of Vibrio parahaemolyticus.•Next most important is newly emerging hepatopancreatic microsporidiosis (HM).•Threats from white spot, yellow head and infectious myonecrosis viruses remain.•The key to stemming current and future crises is renewed, stringent biosecurity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
An acute hepatopancreatic necrosis disease (AHPND) causes serious losses to the global shrimp industry. The etiologic agent of AHPND is Vibrio spp. carrying a large plasmid which encodes a binary ...toxin, PirAB. Currently, AHPND is diagnosed by PCR based methods that detect the presences of both pirA and pirB genes. However, the bacterial strains containing the pirA and pirB genes do not always express the binary toxin, resulting in mis-estimation of the virulence of bacterial strains containing pirA and pirB genes. Thus, the immuno based assay (i.e. ELISA) is a promising approach to detect PirAVp and PirBVp. In the present study, a total of forty monoclonal antibodies clones (mAb) against PirAVp (20 mAbs) and PirBVp (20 mAbs) were screened by western blot analysis to select four mAb clones that show the strongest immunoreactivity in indirect ELISA (iELISA). The four selected mAbs (i.e. 1B9 and 5E9 against PirAVp; 7B7 and 7B9 against PirBVp) detected specifically Vibrio spp. causing AHPND. In addition, four selected mAbs were able to detect either PirAVp or PirBVp down to 0.008 ng/μl. A double blind assay using thirty AHPND-infected and six SPF shrimp Penaeus vannamei were analyzed by iELISA to determine the detection sensitivity of the assay. The results showed that iELISA was able to accurately detect 29 out of 30 AHPND infected shrimp. These finding indicated that iELISA is a reliable method to detect PirAVp and PirBVp toxins in infected shrimp and will be a useful tool in AHPND diagnosis and in studying the role of binary toxins in AHPND pathogenesis.
•An iELISA using mAbs against Photorhabdus insect related toxins, PirAVP and PirBVP produced by Vibrio species was developed.•Four mAbs against PirAVP and PirBVP, that showed strong reactions in western blot analyses were selected for developing iELISA.•Using an iELISA PirAVP & PirBVP were detected in Penaeus vannamei shrimp infected with Vibrio parahaemolyticus causing AHPND.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The maturation and reproduction of Pacific whiteleg shrimp, Penaeus vannamei, through the practice of unilateral eyestalk ablation though common is an animal welfare concern. This study assessed the ...resilience of offspring from non-ablated P. vannamei when challenged with an isolate of Vibrio parahaemolyticus (Vp) causing acute hepatopancreatic necrosis disease (VpAHPND), and with white spot syndrome virus (WSSV). VpAHPND and WSSV challenges were conducted using PL and juveniles under controlled conditions, with both trials using four groups (i.e. shrimp from either ablated or non-ablated females and then either challenged with the pathogen or not challenged). For the VpAHPND challenge, ten replicate 20 L tanks (five replicates for each population) each containing 100 PL 17 (average weight 14 mg) in 15 ppt, 29.05 ± 0.13 °C water were challenged with 2 mL of 2.0 × 108 CFU mL−1 culture of V. parahaemolyticus. A further ten replicate tanks (five per population) served as the corresponding non-challenged controls. The shrimp mortalities were assessed every 3 h over the following 96 h. For the WSSV challenge, individual 1.4 g (average weight) shrimp (50 individuals per population) were housed in 1 L tanks and fed 0.1 g WSSV infected tissue (av. 2.02 × 109 WSSV). A further 50 shrimp per population served as non-challenged controls. The shrimp were maintained at 15 ppt, 26.3 ± 0.71 °C water and assessed every 3 h post-infection over the subsequent 168 h and mortalities at each time point noted. Postlarvae from non-ablated females had significantly (p = 2.4E-23) better survival (70.4%) than those from ablated females (38.8%) at 96 h post-challenge with VpAHPND. Both challenged populations had significantly (p ≤1.3E-36) lower survival than the control groups. The survival of the juveniles from non-ablated females (62%) at 168 h post-infection with WSSV was not significantly higher than that of the juveniles from ablated female (48%) although the difference was significantly different at 65 to 75 h. Both challenged populations also had significantly (p ≤1.0E-5) lower survival rates than the control groups. The study demonstrates that postlarvae and juveniles from non-ablated females are more resilient to typical pathogens (VpAHPND and WSSV) and may show higher survival rates during a disease outbreak.
•Non-ablated Penaeus vannamei females produce offspring that are more resilient to commonly encountered pathogens.•Postlarvae from non-ablated female have a significantly higher resistance to VpAHPND.•Juveniles from non-ablated animals have better survival to WSD than their juvenile counterparts from ablated female.
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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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