Impact of cytogenetic abnormalities on the risk of disease progression in solitary bone plasmacytomas.

Most patients with solitary bone plasmacytomas (SBP) progress to multiple myeloma (MM) after definitive radiation therapy as their primary treatment. Whether the presence of high-risk (HR) cytogenetic abnormalities by fluorescence in situ hybridization (FISH) in the clonal plasma cells, obtained either directly from the diagnostic SBP tissue or the corresponding bone marrow examination at the time of diagnosis, is associated with a shorter time to progression (TTP) to MM is unknown. This study evaluated all patients diagnosed with SBP at the Mayo Clinic from January 2012 to July 2022. The presence of del(17p), t(14;16), t(4;14), or +1q (gain or amplification) by FISH in clonal plasma cells was defined as HR. A total of 114 patients were included in this cohort, and baseline FISH was available for 55 patients (48%), of which 22 were classified as HR (40%). The median TTP to MM for patients with SBP and HR FISH was 8 months (95% confidence interval [CI], 6.3-26) compared with 42 months (95% CI, 25-not reached [NR]) in patients with SBP without HR FISH (P < .001). In a multivariate analysis, only HR FISH was a significant predictor for shorter TTP to MM, independent of minimal marrow involvement and an abnormal serum free light chain ratio at diagnosis. Deletion (17p) and gain 1q abnormalities were the most common FISH abnormalities responsible for the short TTP to MM. Thus, assessing for HR FISH abnormalities in clonal plasma cells derived from either the diagnostic SBP tissue or the staging bone marrow examination of patients with newly diagnosed SBP is feasible and prognostic for a shorter TTP to MM.

Bacillus subtilis NBRI-W9 simultaneously activates SAR and ISR against Fusarium chlamydosporum NBRI-FOL7 to increase wilt resistance in tomato.

AIMS: The study aimed to determine the pathogenicity of Fusarium species currently prevalent in tomato fields having history of chemical fungicide applications and determine the bio-efficacy of Bacillus subtilis NBRI-W9 as a potent biological control agent. METHODS AND RESULTS: Fusarium was isolated from surface-sterilized infected tomato plants collected from fields. Pathogenicity of 30 Fusarium isolates was determined by in vitro and in vivo assays. Following Koch's postulates, F. chlamydosporum (FOL7) was identified as a virulent pathogen. The biological control of FOL 7 by B. subtilis NBRI-W9 (W9) and the colonization potential of W9 were established using spontaneous rifampicin-resistant mutants. W9 showed 82% inhibition of FOL7 on a dual-culture plate and colonization levels in tomato plants of ∼5.5, ∼3.3, and ∼2.2 log10 CFU/g in root, stem, and leaf tissue, respectively. Antagonistic activity was shown by scanning electron microscopy (SEM) and cell-wall-degradative enzymes. W9 reduced FOL7 infection in net-house and field experiments by 60% and 41%, respectively. Biochemical investigation, defence enzymes, defence gene expression analysis, SEM, and field studies provide evidence of hyperparasitism and induced resistance as the mode of biological control. The study also demonstrates that the potent biocontrol agent W9, isolated from Piper, can colonize tomato plants, control fungal disease by inducing induced systemic resistance (ISR) and systemic acquired resistance (SAR) simultaneously, and increase crop yield by 21.58% under field conditions. CONCLUSIONS: This study concludes that F. chlamydosporum (NBRI-FOL7) is a potent, fungicide-resistant pathogen causing wilt in tomatoes. NBRI-W9 controlled FOL7 through mycoparasitism and simultaneously activated ISR and SAR in plants, providing an attractive tool for disease control that acts at multiple levels.

Whole-body low-dose computed tomography in patients with newly diagnosed multiple myeloma predicts cytogenetic risk: a deep learning radiogenomics study.

OBJECTIVE: To develop a whole-body low-dose CT (WBLDCT) deep learning model and determine its accuracy in predicting the presence of cytogenetic abnormalities in multiple myeloma (MM). MATERIALS AND METHODS: WBLDCTs of MM patients performed within a year of diagnosis were included. Cytogenetic assessments of clonal plasma cells via fluorescent in situ hybridization (FISH) were used to risk-stratify patients as high-risk (HR) or standard-risk (SR). Presence of any of del(17p), t(14;16), t(4;14), and t(14;20) on FISH was defined as HR. The dataset was evenly divided into five groups (folds) at the individual patient level for model training. Mean and standard deviation (SD) of the area under the receiver operating curve (AUROC) across the folds were recorded. RESULTS: One hundred fifty-one patients with MM were included in the study. The model performed best for t(4;14), mean (SD) AUROC of 0.874 (0.073). The lowest AUROC was observed for trisomies: AUROC of 0.717 (0.058). Two- and 5-year survival rates for HR cytogenetics were 87% and 71%, respectively, compared to 91% and 79% for SR cytogenetics. Survival predictions by the WBLDCT deep learning model revealed 2- and 5-year survival rates for patients with HR cytogenetics as 87% and 71%, respectively, compared to 92% and 81% for SR cytogenetics. CONCLUSION: A deep learning model trained on WBLDCT scans predicted the presence of cytogenetic abnormalities used for risk stratification in MM. Assessment of the model's performance revealed good to excellent classification of the various cytogenetic abnormalities.

Failure of mobilization of hematopoietic stem cells associated with elevated serum levels of anti-CD38 monoclonal antibody.

Daratumumab is an anti-CD38 antibody that is increasingly incorporated in induction regimens for treating patients with newly diagnosed multiple myeloma (NDMM). Previous reports have demonstrated a lower yield of hematopoietic stem cells (HSCs) after induction with daratumumab; however, none of them reported a failure to collect an adequate number of HSCs. We describe a case of adequate HSC mobilization failure in a patient who inadvertently received excessive doses of daratumumab and was confirmed by higher-than-expected circulating levels of daratumumab by mass spectrometry. Eventual clearance of circulating daratumumab was associated with the successful mobilization and harvesting of HSCs.

Carbendazim Modulates the Metabolically Active Bacterial Populations in Soil and Rhizosphere.

The impact of fungicide residues on non-target soil bacterial communities is relatively unexplained. We hypothesize that the persistence of fungicide residues in the soil will affect the soil bacterial populations. Persistence depends on biotic and abiotic factors, primarily determined by agricultural activities. Activities such as fallow soil (F), farmyard manure (FYM) amendment, rice straw (RS) mulching, and cultivation of maize (Zea mays) and clover (Trifolium alexandrinum) were used as treatments. The soil CO2 efflux showed no effect of Carbendazim on dormant bacteria (unwatered condition). However, in irrigated condition, Carbendazim enhanced the CO2 efflux by 8, 164, 131, 249, and 182% in fallow, FYM, RS, maize, and Trifolium treatments, respectively. However, 16S rRNA metagenome study after 30 days of carbendazim treatment showed that maize rhizosphere microflora was most susceptible, decreasing the Shannon diversity index from 0.321 to 0.165. Diversity indices generally increased in maize and RS treatments, and Proteobacteria was the most prominent bacterial phyla in the maize rhizosphere. The microbial communities separated into distinct groups on the Principal Co-ordinate analysis (PCoA) plot. The separation on scale 1 (35%) and scale 2 (13%) was based, respectively, on microbial activity and carbendazim treatments. Functionally Maize+Carbendazim treatment showed the highest enzyme activities dehydrogenase (82.25%), acid phosphatase (78.10%), alkaline phosphatase (48.26%), ß-glucosidase (59.99%), protease (126.65%), and urease (50.66%) compared to fallow soil. Overall, Carbendazim enhanced non-target bacterial activity in metabolically active niches, while it did not affect the dormant microflora. Thus, organic amendments and cultivation of fungicide-contaminated soil may help render the contaminant through bacterial activity.

Hypertension in Cancer Survivors.

PURPOSE OF REVIEW: With increasing survival after cancer treatment, there is a need for long-term management of risk factors and chronic medical conditions to realize the full benefit of improvement of outcomes. Hypertension is a major risk factor for cardiovascular disease and has a higher prevalence in cancer survivors compared to the general population. In this review article, we discuss the burden of hypertension in cancer survivors and how this impacts their long-term outcomes and risk of cancer recurrence. We then discuss the latest concepts regarding the pathophysiology of hypertension in cancer survivors in detail. There is a focus on inflammation and the role it plays in cancer and hypertension followed by a brief discussion on clonal hematopoiesis of indeterminate potential (CHIP) and associated hypertension. There is a brief review of various cancer therapies associated with development and worsening of hypertension control and the underlying mechanisms behind this. We conclude the review article by giving recommendations on blood pressure control in this unique patient population. RECENT FINDINGS: A lot of newer anti-cancer therapies have been implicated in the development or worsening of hypertension. We summarize the latest data, explore associations between these therapies and hypertension, and review the latest understanding of the underlying mechanisms driving this process. Hypertension is a major risk factor for cardiovascular disease in cancer survivors and must be recognized and treated promptly.

Synergistic action of Trichoderma koningiopsis and T. asperellum mitigates salt stress in paddy.

Intensive cultivation increases the salinity and alkalinity of soil leading to its degradation. Such soil lead to abiotic stress conditions in plants causing ROS-mediated cellular damage. Microbes constitute an important group of bio-stimulants, which are promising alternatives to reduce ROS-mediated abiotic stresses and improve plant growth. In the present study synergistic activity of stress-tolerant Trichoderma koningiopsis NBRI-PR5 (MTCC 25372) and T. asperellum NBRI-K14 (MTCC 25373) (TrichoMix) was assessed in paddy crop under salt stress conditions. Improved soil microbial biomass carbon (MBC), total organic carbon (TOC), and available nutrients N/P/K by 2-3 folds was observed in the pot experiment using the TrichoMix. It restored the heterogeneous microbial population of the paddy rhizosphere during salt stress and modulated the soil enzyme activities. The anatomical distortions in rice roots due to salt stress were stabilized in presence of the TrichoMix. Different stress marker genes (OsMAPK5, OsAPX, OsGST, OsUSP, OsBADH, OsLYSO, OsNRAMP6, and OsBz8) were differentially modulated by the TrichoMix in presence of salt stress as compared to the control. The TrichoMix increased the yield by 10% in marginally stressed fields; however, it enhanced the yield by approximately 60% when used with the 50% recommended dose of NPK. In the integrated treatment, Fe and Zn were fortified by approximately 40% and 29% respectively in the grains. From the present study, it was concluded that the TrichoMix stimulated the rice plants to accumulate osmoprotectants, improved the anatomical features, modulated the plant defense system, and improved the grain yield and quality. Therefore, the NBRI-PR5 and NBRI-K14 mixture may be used as a bio-stimulant to increase productivity in the rapidly deteriorating soil and reduce the NPK inputs. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01192-6.

Efficacy of Upfront Docetaxel With Androgen Deprivation Therapy for Castration-Sensitive Metastatic Prostate Cancer Among Minority Patients.

BACKGROUND: Upfront docetaxel (UD) with androgen deprivation therapy (ADT) has been demonstrated to improve survival outcomes in metastatic castration-sensitive prostate cancer (mCSPC). However, existing studies have included predominantly Caucasian patients. STUDY QUESTION: To compare the efficacy of addition of UD to ADT in mCSPC to ADT alone among minority patients. STUDY DESIGN: Retrospective study of mCSPC patients. MEASURES AND OUTCOMES: Patients treated with UD and ADT between January 2014 and December 2017 (UD + ADT, n = 44) were compared with those treated with ADT alone between January 2008 and January 2017 (ADT, n = 38); patients of Caucasian ethnicity were excluded. The outcome of interest was progression-free survival (PFS), which was estimated using Kaplan-Meier analysis and Cox proportional hazard analysis. RESULTS: Overall, 63 (76.8%) patients were African American and 16 (19.5%) were Hispanic. Fifty-five (67%) patients had high-volume mCSPC. The median follow-up was 14 months [95% confidence interval (CI): 10.4-16.5] for UD + ADT and 42 months (95% CI: 17-66.9) for ADT. Median PFS did not differ between groups: UD + ADT: 16 versus ADT: 18 months [hazard ratio (HR) for UD + ADT = 0.88, 95% CI: 0.48-1.62; P = 0.70]. In patients with high-volume disease, median PFS remained similar (UD + ADT: 16 vs. ADT: 14 months (HR for UD + ADT = 0.64, 95% CI: 0.33-1.25; P = 0.19). On multivariable analysis, prolonged time to nadir PSA, HR = 0.83 (95% CI: 0.76-0.90), was independently associated with PFS. The most common toxicities in UD + ADT were anemia and fatigue. Major limitations include small sample size and potential for selection bias due to the retrospective study design. CONCLUSIONS: In this retrospective review of a minority mCSPC cohort, UD + ADT was not associated with improved PFS compared with ADT alone. Although further study with larger sample size is needed, these results underscore the importance of ensuring accrual of minorities in clinical trials, reflective of the real-world setting.

Endophytic biofungicide Bacillus subtilis (NBRI-W9) reshapes the metabolic homeostasis disrupted by the chemical fungicide, propiconazole in tomato plants to provide sustainable immunity against non-target bacterial pathogens.

Chemical and microbial fungicides (Bio/fungicide) act differentially on plant systems. The present work assessed the metabolic profile of tomato plants vis-a-vis endophytic diversity after spraying of Propiconazole (PCZ) and endophytic biofungicide Bacillus subtilis (W9). Bio/fungicides were sprayed on tomato plants and evaluated for phenotypic, biochemical, and metabolic profiles after one week. In W9 treatment, a significant increase in relative abundance of several metabolites was observed including sugars, sugar alcohols, fatty-acids, organic-acids, and amino-acids. Polysaccharides and fatty acids showed a significant positive correlation with Rhizobiales, Burkholderiales, Bacillales, and Lactobacillales, respectively (p < 0.05). The PCZ and W9 treated plant's metabolic status significantly affected their resistance to non-target, bacterial pathogen P. syringae. Compared to PCZ and control, W9 treatment reduced the ROS deposition and expression of antioxidants gene GPx, PO (~0.1-1.7fold). It enhanced the genes related to the Phenylpropanoid pathway (∼1.6-5.2 fold), PR protein (~1.2-3.4 fold), and JA biosynthesis (~1.7-4.3 fold), resulting in reduced disease incidence. The results provide novel insights into the effects of endophytic biofungicide and chemical fungicides on the plant's metabolic status, its relation to the endophytes, and role in altering the plant's immune system.

Role of the PLASMIC Score in the Management of Thrombotic Thrombocytopenic Purpura.

We report the case of a middle-aged male presenting with fatigue and abdominal pain. Prompt investigations demonstrated microangiopathic hemolytic anemia and thrombocytopenia on a peripheral blood smear. Thrombotic thrombocytopenic purpura was suspected based on the PLASMIC score. The patient significantly improved with therapeutic plasma exchange and prednisone within the next few days. The disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 levels reduction is a definitive hallmark leading to microvascular thrombosis. However, some medical centers in the United States do not promptly have quick allowance to the levels. Hence, the PLASMIC score becomes imminent in initiating immediate management and preventing life-threatening complications.

An Insight into the Endophytic Bacterial Community of Tomato after Spray Application of Propiconazole and Bacillus subtilis Strain NBRI-W9.

Propiconazole (PCZ) is a commonly sprayed fungicide against fungal pathogens. Being systemic in action, it reaches subcellular layers and impacts the endophytes. Although PCZ is a fungicide, it is hypothesized to exert an inhibitory effect on the bacterial endophytes. Therefore, this study aims to get an insight into the perturbations caused by the systemically acting antifungal agents PCZ and Bacillus subtilis (W9) and the consequences thereof. The current study compared the 16S rRNA microbial diversity, abundance, and functions of the endophytic bacterial community of tomato in response to PCZ, W9, and PCZ+W9 application. The implications of these treatments on the development of bacterial speck disease by Pseudomonas syringae were also studied. The culturable endophyte population fluctuated after (bio)fungicide application and stabilized by 72 h. At 72 h, the endophyte population was ~3.6 × 103 CFUg-1 in control and ~3.6 × 104 in W9, ~3.0 × 102 in PCZ, and ~5.3 × 103 in PCZ+W9 treatment. A bacterial community analysis showed a higher relative abundance of Bacillales, Burkholderiales, Rhizobiales, Pseudomonadales, and Actinomycetales in the W9 treatment compared with that in the PCZ treatment and control. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis showed enhanced metabolic pathways related to secretion, stress, chemotaxis, and mineral nutrition in the W9 treatment. Disease severity was greater in PCZ than that in the W9 treatment. Disease severity on tomato plants showed strong negative correlations with Sphingomonas (r = -0.860) and Janthinobacterium (r = -0.810), indicating that the natural biocontrol communities are agents of plant resistance to diseases. Outcomes show that systemic chemicals are a potential threat to the nontarget endophytes and that plants became susceptible to disease on endophyte decline; this issue could be overcome by the application of microbial inoculums. IMPORTANCE Endophytes are plant inhabitants acting as its extended genome. The present study highlights the importance of maintaining plant endophytes for sustainable disease resistance in plants. The impact of chemical fungicides and biofungicides was shown on tomato endophytes, in addition to their implications on plant susceptibility to bacterial speck disease. The observations point toward the deleterious effects of systemic pesticide application on endophyte niches that disrupt their diversity and functions compromising plant immunity.

Primary pericardial angiosarcoma: case report and review of treatment options.

A primary cardiac angiosarcoma is a rare type of soft-tissue sarcoma with a high mortality rate. This report describes a young woman who presented with chest pain and worsening shortness of breath over the course of a year. She was diagnosed with and treated for latent tuberculosis and autoimmune pericarditis over the last year, however, her condition kept worsening. Further workup revealed a large pericardial and right atrial mass associated with multiple lung nodules. The biopsy from the lung mass showed angiosarcoma, and she was diagnosed with primary metastatic angiosarcoma of the pericardium. She was treated with doxorubicin and Ifosfamide (AIM-75 regimen), which led to a partial response. However, soon after completion of six cycles, the tumour progressed rapidly, leading to cardio-respiratory failure. In this report, we will discuss the clinical challenges and treatment options (surgical and medical) that are available for treating patients with angiosarcoma of the heart.

Alcohol abuse and alcoholic liver cirrhosis leading to spontaneous muscle hematoma: an event fraught with danger.

Alcohol abuse is associated with both potentiating and antagonizing hemostatic states. Liver cirrhosis is an independent causal factor for many bleeding complications. The long-term effects of alcohol abuse coupled with advanced liver cirrhosis are additive in favor of bleeding. We report the case of a patient with a history of alcohol abuse who presented with liver cirrhosis and nontraumatic muscle hematoma diagnosed as a spontaneous hematoma of the gastrocnemius muscle. He was managed conservatively with infusions of fresh frozen plasma and platelets, which resulted in resolution of the hematoma. The pathogenesis of 'spontaneous' muscle hematoma remains anecdotal, but since it is reported in patients on anticoagulant therapy or with hemostatic disorders, it is hypothetically related to severely deranged coagulation. Here we review the relevant literature pertaining to the pathogenesis, presentation and treatment options available for treating this often fatal complication of bleeding diatheses.