Gut microbiome composition and response to sunitinib in metastatic renal cell carcinoma (mRCC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 657-657 ◽  
Author(s):  
Jun Gong ◽  
Nazli Dizman ◽  
Valeriy Poroyko ◽  
Haejung Won ◽  
Cristiane Decat Bergerot ◽  
...  

657 Background: Recent evidence supports a link between stool microbiome composition and immunotherapy response. However, it is unclear how the microbiome may influence clinical outcome in mRCC where vascular endothelial growth factor-targeted therapies remains a standard of care. Methods: Five consecutive stool samples were collected at baseline and at weeks 2, 3, 4 and 12 of treatment with sunitinib in patients (pts) with mRCC. In responders (R: complete/partial response and stable disease) and non-responders (P: primary progression), gut microbiota composition was assessed through extraction of microbial DNA where 16s RNA gene tags (v4) were generated by PCR amplification and sequenced using MiSeq (Illumina). Sequence reads were processed by Mothur software, assembled in Operational Taxonomic Units (OTUs), taxonomically annotated to the genus level, and used to construct Bray-Curtis dissimilarity matrix. The similarity of samples was visualized by principle coordinate (PCo) analysis and further confirmed by k-means clustering and ANOSIM tests. Differentially abundant taxa were determined by METASTATS. Results: Stool bacteriomic profiling identified 25,304 OTUs attributable to 165 genera from 8 phyla in 4 of 6 pts evaluable for response. PCo analysis revealed clear separation of R and P (accounting for 28.9 % of dataset variation) where subsequent k-means clustering confirmed the difference of microbiota in 2 clusters that perfectly align with R and P groups. The significance of this separation was confirmed by ANOSIM analysis (p = 0.005). Analysis of microbiota composition in P and R groups revealed 14 differentially abundant taxonomic units at the genus level. Of those at ≥1% abundance, Bacteroides, Barnesiella and Phascolarctobacterium were elevated in R, while Bifidobacterium and Dorea were elevated in P (p < 0.01 for all). Of those at < 1% abundance, Lactococcus, Sporobacter, Acidaminococcus, Actinomyces, and Asaccharobacter were elevated in P (p < 0.01 for all). Conclusions: Although limited by sample size, we report the first in-human study to suggest a link between microbiota and response to sunitinib as we identified a significant discrepancy in stool bacteriomic distribution between P and R.

Author(s):  
E.V. Korneenko ◽  
◽  
А.E. Samoilov ◽  
I.V. Artyushin ◽  
M.V. Safonova ◽  
...  

In our study we analyzed viral RNA in bat fecal samples from Moscow region (Zvenigorod district) collected in 2015. To detect various virus families and genera in bat fecal samples we used PCR amplification of viral genome fragments, followed by high-throughput sequencing. Blastn search of unassembled reads revealed the presence of viruses from families Astroviridae, Coronaviridae and Herpesviridae. Assembly using SPAdes 3.14 yields contigs of length 460–530 b.p. which correspond to genome fragments of Coronaviridae and Astroviridae. The taxonomy of coronaviruses has been determined to the genus level. We also showed that one bat can be a reservoir of several virus genuses. Thus, the bats in the Moscow region were confirmed as reservoir hosts for potentially zoonotic viruses.


Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 48
Author(s):  
Junya Saeki ◽  
Soichiro Iwanuma ◽  
Suguru Torii

The structure of the first toe is independent of that of the other toes, while the functional difference remains unclear. The purpose of this study was to investigate the difference in the force generation characteristics between the plantar-flexion of the first and second–fifth metatarsophalangeal joints (MTPJs) by comparing the maximal voluntary plantar-flexion torques (MVC torque) at different MTPJs and ankle positions. The MVC torques of the first and second–fifth MTPJs were measured at 0°, 15°, 30°, and 45° dorsiflexed positions of the MTPJs, and at 20° plantar-flexed, neutral, and 20° dorsiflexed positions of the ankle. Two-way repeated measures analyses of variance with Holm’s multiple comparison test (MTPJ position × ankle position) were performed. When the MTPJ was dorsiflexed at 0°, 15°, and 30°, the MVC torque of the first MTPJ when the ankle was dorsiflexed at 20° was higher than that when the ankle was plantar-flexed at 20°. However, the ankle position had no significant effect on the MVC torque of the second–fifth MTPJ. Thus, the MVC torque of the first MTPJ was more affected by the ankle position than the second–fifth MTPJs.


2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S29-S30
Author(s):  
Tomer Lagziel ◽  
Louis J Born ◽  
Luis H Quiroga ◽  
Eliana Duraes ◽  
Pragna N Shetty ◽  
...  

Abstract Introduction Topical delivery of antibacterial agents is typically incorporated and is an essential component of burn wound therapy. The goal is to prevent infection and promote the healing process. Poorly treated wounds can result in scarring or severely in sepsis and multi-organ dysfunction. Topical SSD cream has been the gold-standard for initial local care in partial thickness or full thickness burns. Due to immediate burst release of the drug into the exposed areas, application is relatively frequent (usually twice daily). However, it remains unknown whether twice-daily SSD dressings are superior to once-daily. Methods We maintained a twice-daily dressing change standard of care until 01/01/2019. Patients admitted after that date had their dressing changed once-daily. Our goal is to review outcomes for 75 patients before the change-of-practice and 75 patients after. The main outcomes recorded are wound infection rates, hospital-acquire complications (non-wound related), pain scores, daily narcotic requirements, average amount of SSD used, and length-of-stay. Results Preliminary results of the 75 pre-change-of-practice and 75 post-change-of-practice patients showed slightly better outcomes in the post-change group. Wound-infection rates were the same for both groups (pre=5.33%, post=5.33%), average daily pain-levels for the pre-change group were slightly higher but the difference was negligible and not statistically significant (pre=5.76, post=5.69). The pre-change group had a higher average daily narcotic dosage (pre=6.81mg, post=6.38mg), hospital-acquired complication rates were higher pre-change (pre=10.67%, post=6.67%), and length-of-stay was longer in the pre-change group (pre=10.81, post=9.25). The average amount of SSD jars used per patient was higher as well (pre=6.30, post=2.85). Statistical analysis of the distribution of burn type, age, and burn depth showed no discrepancy and a generalized decreased length-of-stay with once-daily SSD dressing change. Conclusions Preliminary results show that once-daily dressing changes of SSD in burn wounds have no negative impact on wound outcomes. However, it is associated with a decreased length-of-stay, decreased pain levels, and less hospital-acquired complications. A decreased length-of-stay means reduced medical expenses for the patient and the hospital. In addition, less hospital-acquired complications result in better patient recovery. Since the difference in wound outcomes is negligible and statistically insignificant, changing the standard-of-care to once-daily could prove beneficial.


2021 ◽  
pp. 089719002110212
Author(s):  
Brandy Williams ◽  
Justin Muklewicz ◽  
Taylor D. Steuber ◽  
April Williams ◽  
Jonathan Edwards

Background: Shifting inpatient antibiotic treatment to outpatient parenteral antimicrobial therapy may minimize treatment for acute bacterial skin and skin structure infections, including cellulitis. The purpose of this evaluation was to compare 30-day hospital readmission or admission due to cellulitis and economic outcomes of inpatient standard-of-care (SoC) management of acute uncomplicated cellulitis to outpatient oritavancin therapy. Methods: This retrospective, observational cohort study was conducted at a 941-bed community teaching hospital. Adult patients 18 years and older treated for acute uncomplicated cellulitis between February 2015 to December 2018 were eligible for inclusion. Information was obtained from hospital and billing department records. Patients were assigned to either inpatient SoC or outpatient oritavancin cohorts for comparison. Results: 1,549 patients were included in the study (1,348 in the inpatient SoC cohort and 201 in the outpatient oritavancin cohort). The average length of stay for patients admitted was 3.6 ± 1.5 days. The primary outcome of 30-day hospital readmission or admission due to cellulitis occurred in 49/1348 (3.6%) patients in the inpatient SoC cohort versus 1/201 (0.5%) in the outpatient oritavancin cohort (p = 0.02). The difference between costs and reimbursement was improved in the outpatient oritavancin group (p < 0.001). Conclusion: Outpatient oritavancin for acute uncomplicated cellulitis was associated with reduction in 30-day hospital readmissions or admissions compared to inpatient SoC. Beneficial economic outcomes for the outpatient oritavancin cohort were observed. Additional studies are required to confirm these findings.


2021 ◽  
Vol 9 (8) ◽  
pp. 1571
Author(s):  
Rotem Sela ◽  
Sivan Laviad-Shitrit ◽  
Leena Thorat ◽  
Bimalendu B. Nath ◽  
Malka Halpern

Chironomids (Diptera; Chironomidae) are aquatic insects that are abundant in freshwater. We aimed to study the endogenous microbiota composition of Chironomus ramosus larvae that were sampled from the Mutha River and a laboratory culture in India. Furthermore, we performed a metagenomic analysis of the larval microbiome, sampled from the Mutha River. Significant differences were found between the bacterial community composition of C. ramosus larvae that were sampled from the Mutha River and the laboratory culture. A total of 54.7% of the amplicon sequence variants (ASVs) that were identified in the larvae from the Mutha River were unique, compared to only 12.9% of unique ASVs that were identified from the laboratory-reared larvae. The four most abundant phyla across all samples were: Proteobacteria, Fusobacteria, Firmicutes, and Bacteroidetes, while the nine most abundant genera were: Aeromonas, Alkanindiges, Breznakia, Cetobacterium, Chryseobacterium, Desulfovibrio, Dysgonomonas, Thiothrix, and Vibrio. Moreover, in the metagenomic analysis, we detected bacterial genes and bacterial pathways that demonstrated the ability to degrade different toxic compounds, detoxify metal, and confer resistance to antibiotics and UV radiation, amongst other functions. The results illuminate the fact that there are detoxifying enzymes in the C. ramosus larval microbiome that possibly play a role in protecting the insect in polluted environments.


2021 ◽  
Vol 10 (5) ◽  
pp. 1097
Author(s):  
Jeong-Ju Yoo ◽  
Hee Shin ◽  
Ju Song ◽  
Minjung Kim ◽  
Jina Yun ◽  
...  

Traditionally, the diagnostic mainstay of recurrent urinary tract infection has been urinary culture. However, the causative uropathogen of recurrent cystitis has not been well established. Urine DNA next-generation sequencing (NGS) can provide additional information on these infections. Herein, we compared urine NGS results and urine cultures in patients with acute uncomplicated cystitis (AUC) and recurrent cystitis (RC), and evaluated the difference in microbiome patterns in the NGS results. Patients who underwent urine culture and NGS due to AUC or RC were retrospectively reviewed. All urine samples were collected via a transurethral catheter and studied utilizing a type of NGS called 16S ribosomal RNA gene amplification and sequencing. The sensitivity of urine NGS was significantly higher than that of conventional urine culture (69.0% vs. 16.7%, p < 0.05). The detection rate of urine NGS was slightly lower in the RC group than in the AUC group (67.7% vs. 72.7%). Microbiome diversity was significantly higher in the RC group compared to the AUC group (p = 0.007), and the microbiome composition was significantly different between the AUC and RC groups. In the urine NGS results, Pseudomonas, Acinetobacter, and Enterobacteriaceae were found in the AUC group, and Sphingomonas, Staphylococcus, Streptococcus, and Rothia spp. were detected in the RC group. Urine NGS can significantly increase the diagnostic sensitivity compared to traditional urine culture methods, especially in RC patients. AUC and RC patients had significant differences in bacterial diversity and patterns. Therefore, recurrent cystitis might be approached from a different perspective.


Author(s):  
Julia Gonzalez ◽  
Diana Carolina Andrade ◽  
JianLi Niu

Abstract Background Acute bacterial skin and skin structure infections (ABSSSIs) are common infectious diseases that cause a significant economic burden on the healthcare system. This study aimed to compare the cost-effectiveness of dalbavancin vs standard of care (SoC) in the treatment of ABSSSI in a community-based healthcare system. Methods This was a retrospective study of adult patients with ABSSSI treated with dalbavancin or SoC during a 27-month period. Patients were matched based on age and body mass index. The primary outcome was average net cost of care to the healthcare system per patient, calculated as the difference between reimbursement payments and the total cost to provide care to the patient. The secondary outcome was proportion of cases successfully treated, defined as no ABSSSI-related readmission within 30 days after the initiation of treatment. Results Of the 418 matched patients, 209 received SoC and 209 received dalbavancin. The average total cost of care per patient was greater with dalbavancin vs SoC ($4770 vs $2709, P &lt; .0001). The average reimbursement per patient was $3084 with dalbavancin vs $2633 SoC (P = .527). The net cost, calculated as revenue minus total cost, was $1685 with dalbavancin vs $75 with SoC (P = .013). The overall treatment success rate was 74% with dalbavancin vs 85% with SoC (P = .004). Conclusions Dalbavancin was more costly than SoC for the treatment of ABSSSI, with a higher 30-day readmission rate. Dalbavancin does not offer an economic or efficacy advantage.


mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Lauren E. Fuess ◽  
Stijn den Haan ◽  
Fei Ling ◽  
Jesse N. Weber ◽  
Natalie C. Steinel ◽  
...  

ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems.


2019 ◽  
pp. 299-334
Author(s):  
Lucy Jones

This chapter discusses the difference between the law of torts and contract and criminal law. It explores the tort of negligence, considering the necessary elements for a claim of negligence, namely the defendant owed the claimant a duty of care, the defendant breached that duty of care, and reasonably foreseeable damage was caused by the breach of duty. The chapter considers the special requirements for the recovery of pure economic loss and for loss as a result of psychiatric injuries, looking at both primary and secondary victims. The principles relating to breach of a duty of care, including the standard of care, are discussed. The chapter concludes with a discussion of the final element, considering the need for a causal link between the breach of duty by the defendant and the damage suffered by the claimant.


2019 ◽  
pp. 089719001987257
Author(s):  
Francis J. Zamora ◽  
Rani P. Madduri ◽  
Ashmi A. Philips ◽  
Nancy Miller ◽  
Mini Varghese

Background: Appropriate pain control is one of the cornerstones necessary to promote positive clinical outcomes. A new bupivacaine liposomal formulation was designed to extend its analgesic effect for up to 72-hours post-surgery, reportedly leading to significant opioid-sparing. Method: Retrospective and prospective chart review conducted in a 178-bed academic institution between January 2013 to December 2013 and August 2014 to November 2014, in 115 patients that receive hip and knee arthroplasty. The primary outcome was the measurement of average daily pain score on post-operative days 1 and 2. Secondary outcomes included length of stay, overall opioid use post-surgery and pain control satisfaction using Press-Ganey® scores. Results: The average pain scores in the HCl group were 4.64 and 4.38 (Likert score: 0-10) for POD 1 and POD 2, compared to 4.72 POD 1 and 4.2 POD 2 in the liposome group (POD 1: p = 0.413; POD 2: p = 0.303). The difference in LOS for knee arthroplasty was statistically significant [HCl group: 1.94 days (± 0.66) versus liposome group: 2.27 days (±0.77) p-value = 0.038)] favoring the standard of care. For hip arthroplasty or bilateral knee arthroplasty the differences in LOS were not statistically significant ( p = 0.052 and p = 0.484 respectively). 93% of the patients in the HCl group, pain was well controlled, versus 88.5% in the liposome group with similar oxycodone IR use among groups. Conclusion: Liposome bupivacaine did not offer a notable benefit compared to the HCl formulation in our study.


Sign in / Sign up

Export Citation Format

Share Document