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.
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.
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.
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.
A new emerging disease in shrimp, first reported in 2009, was initially named early mortality syndrome (EMS). In 2011, a more descriptive name for the acute phase of the disease was proposed as acute ...hepatopancreatic necrosis syndrome (AHPNS). Affecting both Pacific white shrimp Penaeus vannamei and black tiger shrimp P. monodon, the disease has caused significant losses in Southeast Asian shrimp farms. AHPNS was first classified as idiopathic because no specific causative agent had been identified. However, in early 2013, the Aquaculture Pathology Laboratory at the University of Arizona was able to isolate the causative agent of AHPNS in pure culture. Immersion challenge tests were employed for infectivity studies, which induced 100% mortality with typical AHPNS pathology to experimental shrimp exposed to the pathogenic agent. Subsequent histological analyses showed that AHPNS lesions were experimentally induced in the laboratory and were identical to those found in AHPNS-infected shrimp samples collected from the endemic areas. Bacterial isolation from the experimentally infected shrimp enabled recovery of the same bacterial colony type found in field samples. In 3 separate immersion tests, using the recovered isolate from the AHPNS-positive shrimp, the same AHPNS pathology was reproduced in experimental shrimp with consistent results. Hence, AHPNS has a bacterial etiology and Koch's Postulates have been satisfied in laboratory challenge studies with the isolate, which has been identified as a member of the Vibrio harveyi clade, most closely related to V. parahemolyticus.
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.
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.
Background
Several important treatment and supportive care strategies have been implemented over the past 4 decades in the management of acute myeloid leukemia (AML).
Methods
The authors identified ...29,107 patients who were diagnosed with de novo AML between 1980 and 2017 in the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Patients were categorized into 5 age groups (ages birth to 14, 15‐39, 40‐59, 60‐69, and ≥70 years) and 4 calendar periods (1980‐1989, 1990‐1999, 2000‐2009, and 2010‐2017). The outcomes of patients who had AML within these categories were analyzed.
Results
The overall 5‐year survival rates in patients with AML were 9%, 15%, 22%, and 28% in the decades 1980 to 1989, 1990 to 1999, 2000 to 2009, and 2010 to 2017, respectively. Among patients aged 15 to 39 years, the 5‐year survival rates were 24%, 41%, 52%, and 63%, respectively; among those aged ≥70 years, the 5‐year survival rates were 1%, 2%, 3%, and 5%, respectively. Four‐week mortality was surprising high among adults and older patients (range, 20%‐45%), even in modern times. Overall, survival continued to improve over the calendar periods and was best in the period from 2010 to 2017. Survival improvement was noticeable across all age groups except patients aged ≥70 years, in whom the estimated 5‐year survival rate remained 5% even during the period from 2010 to 2017.
Conclusions
The outcomes of patients with AML showed incremental improvement over time in a population‐based study of the Surveillance, Epidemiology, and End Results data. The introduction since 2017 of targeted therapies among older patients and optimizations in supportive care hopefully will continue to improve outcomes in AML, particularly among older patients.
The outcome of patients with acute myeloid leukemia demonstrates incremental improvement over time in a population‐based study of the National Cancer Institute's Surveillance, Epidemiology, and End Results data. For older patients with acute myeloid leukemia, the introduction since 2017 of targeted therapies and optimizations in supportive care hopefully will continue to improve outcomes.
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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