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1.
Can Vet J ; 61(3): 263-266, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32165749

RESUMO

A 13-year-old cat underwent an extensive caudal external hemipelvectomy to excise a soft tissue sarcoma affecting the left proximal thigh. The cranial tibial fascia was harvested from the ipsilateral limb following amputation and used as a free graft in the reconstruction of the resultant pelvic and abdominal wall defect. Wound healing was uncomplicated, and 6 months following surgery there was no evidence of tumor recurrence or loss of integrity of the abdominal wall or lateral rectal support. Key clinical message: The cranial tibial fascia appears to be an effective autograft tissue for reconstructive surgery and may be applicable for closure of extensive hemipelvectomy procedures performed for tumors affecting the femoral region.

2.
Cochrane Database Syst Rev ; 2: CD012466, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32103487

RESUMO

BACKGROUND: Approximately half of people with heart failure have chronic kidney disease (CKD). Pharmacological interventions for heart failure in people with CKD have the potential to reduce death (any cause) or hospitalisations for decompensated heart failure. However, these interventions are of uncertain benefit and may increase the risk of harm, such as hypotension and electrolyte abnormalities, in those with CKD. OBJECTIVES: This review aims to look at the benefits and harms of pharmacological interventions for HF (i.e., antihypertensive agents, inotropes, and agents that may improve the heart performance indirectly) in people with HF and CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies through 12 September 2019 in consultation with an Information Specialist and using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials of any pharmacological intervention for acute or chronic heart failure, among people of any age with chronic kidney disease of at least three months duration. DATA COLLECTION AND ANALYSIS: Two authors independently screened the records to identify eligible studies and extracted data on the following dichotomous outcomes: death, hospitalisations, worsening heart failure, worsening kidney function, hyperkalaemia, and hypotension. We used random effects meta-analysis to estimate treatment effects, which we expressed as a risk ratio (RR) with 95% confidence intervals (CI). We assessed the risk of bias using the Cochrane tool. We applied the GRADE methodology to rate the certainty of evidence. MAIN RESULTS: One hundred and twelve studies met our selection criteria: 15 were studies of adults with CKD; 16 studies were conducted in the general population but provided subgroup data for people with CKD; and 81 studies included individuals with CKD, however, data for this subgroup were not provided. The risk of bias in all 112 studies was frequently high or unclear. Of the 31 studies (23,762 participants) with data on CKD patients, follow-up ranged from three months to five years, and study size ranged from 16 to 2916 participants. In total, 26 studies (19,612 participants) reported disaggregated and extractable data on at least one outcome of interest for our review and were included in our meta-analyses. In acute heart failure, the effects of adenosine A1-receptor antagonists, dopamine, nesiritide, or serelaxin on death, hospitalisations, worsening heart failure or kidney function, hyperkalaemia, hypotension or quality of life were uncertain due to sparse data or were not reported. In chronic heart failure, the effects of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) (4 studies, 5003 participants: RR 0.85, 95% CI 0.70 to 1.02; I2 = 78%; low certainty evidence), aldosterone antagonists (2 studies, 34 participants: RR 0.61 95% CI 0.06 to 6.59; very low certainty evidence), and vasopressin receptor antagonists (RR 1.26, 95% CI 0.55 to 2.89; 2 studies, 1840 participants; low certainty evidence) on death (any cause) were uncertain. Treatment with beta-blockers may reduce the risk of death (any cause) (4 studies, 3136 participants: RR 0.69, 95% CI 0.60 to 0.79; I2 = 0%; moderate certainty evidence). Treatment with ACEi or ARB (2 studies, 1368 participants: RR 0.90, 95% CI 0.43 to 1.90; I2 = 97%; very low certainty evidence) had uncertain effects on hospitalisation for heart failure, as treatment estimates were consistent with either benefit or harm. Treatment with beta-blockers may decrease hospitalisation for heart failure (3 studies, 2287 participants: RR 0.67, 95% CI 0.43 to 1.05; I2 = 87%; low certainty evidence). Aldosterone antagonists may increase the risk of hyperkalaemia compared to placebo or no treatment (3 studies, 826 participants: RR 2.91, 95% CI 2.03 to 4.17; I2 = 0%; low certainty evidence). Renin inhibitors had uncertain risks of hyperkalaemia (2 studies, 142 participants: RR 0.86, 95% CI 0.49 to 1.49; I2 = 0%; very low certainty). We were unable to estimate whether treatment with sinus node inhibitors affects the risk of hyperkalaemia, as there were few studies and meta-analysis was not possible. Hyperkalaemia was not reported for the CKD subgroup in studies investigating other therapies. The effects of ACEi or ARB, or aldosterone antagonists on worsening heart failure or kidney function, hypotension, or quality of life were uncertain due to sparse data or were not reported. Effects of anti-arrhythmic agents, digoxin, phosphodiesterase inhibitors, renin inhibitors, sinus node inhibitors, vasodilators, and vasopressin receptor antagonists were very uncertain due to the paucity of studies. AUTHORS' CONCLUSIONS: The effects of pharmacological interventions for heart failure in people with CKD are uncertain and there is insufficient evidence to inform clinical practice. Study data for treatment outcomes in patients with heart failure and CKD are sparse despite the potential impact of kidney impairment on the benefits and harms of treatment. Future research aimed at analysing existing data in general population HF studies to explore the effect in subgroups of patients with CKD, considering stage of disease, may yield valuable insights for the management of people with HF and CKD.

3.
Nature ; 579(7797): 123-129, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32103176

RESUMO

A mosaic of cross-phylum chemical interactions occurs between all metazoans and their microbiomes. A number of molecular families that are known to be produced by the microbiome have a marked effect on the balance between health and disease1-9. Considering the diversity of the human microbiome (which numbers over 40,000 operational taxonomic units10), the effect of the microbiome on the chemistry of an entire animal remains underexplored. Here we use mass spectrometry informatics and data visualization approaches11-13 to provide an assessment of the effects of the microbiome on the chemistry of an entire mammal by comparing metabolomics data from germ-free and specific-pathogen-free mice. We found that the microbiota affects the chemistry of all organs. This included the amino acid conjugations of host bile acids that were used to produce phenylalanocholic acid, tyrosocholic acid and leucocholic acid, which have not previously been characterized despite extensive research on bile-acid chemistry14. These bile-acid conjugates were also found in humans, and were enriched in patients with inflammatory bowel disease or cystic fibrosis. These compounds agonized the farnesoid X receptor in vitro, and mice gavaged with the compounds showed reduced expression of bile-acid synthesis genes in vivo. Further studies are required to confirm whether these compounds have a physiological role in the host, and whether they contribute to gut diseases that are associated with microbiome dysbiosis.


Assuntos
Ácidos e Sais Biliares/biossíntese , Ácidos e Sais Biliares/química , Metabolômica , Microbiota/fisiologia , Animais , Ácidos e Sais Biliares/metabolismo , Ácido Cólico/biossíntese , Ácido Cólico/química , Ácido Cólico/metabolismo , Fibrose Cística/genética , Fibrose Cística/metabolismo , Fibrose Cística/microbiologia , Vida Livre de Germes , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Camundongos , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo
4.
JAMA Netw Open ; 3(2): e200222, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32108896

RESUMO

Importance: Comparative outcome data examining the association of dialysis initiation with hospital length of stay and intensity of care in older adults with kidney failure are scarce, and prior studies are limited to patients treated by nephrology teams. Objective: To compare in-hospital days and intensity of care among older adults with kidney failure who were treated vs not treated with maintenance dialysis. Design, Setting, and Participants: This population-based, retrospective cohort study included adults in Alberta, Canada, 65 years or older with kidney failure, defined by at least 2 consecutive outpatient estimated glomerular filtration rate values of less than 10 mL/min/1.73 m2 spanning a period of at least 90 days from May 15, 2002, to March 31, 2014. Data were analyzed from August 1, 2017, to August 29, 2019. Exposures: Time-varying exposure to maintenance dialysis for treatment of kidney failure. Main Outcomes and Measures: The primary outcome was rate of in-hospital days. Secondary outcomes included rates of hospital admissions, intensive care unit admissions, cardiopulmonary resuscitations, inpatient palliative care, and emergency department visits; risk of in-hospital death; and time to admission to long-term care. Results: A total of 968 patients (median age, 78.5 [interquartile range, 72.4-84.7] years; 489 men [50.5%]; median follow-up, 2.0 [interquartile range, 0.8-3.9] years) were included in the analysis. Patients who underwent dialysis spent more adjusted in-hospital days per person-year (36.25 [95% CI, 30.72-41.77] vs 14.65 [95% CI, 12.28-17.02]; incidence rate ratio [IRR], 2.47 [95% CI, 1.99-3.08]). However, the dialysis group did not have a higher rate of hospital admissions (1.18 [95% CI 1.07-1.29] vs 1.32 [95% CI 1.17-1.48] per year; IRR, 0.89 [95% CI, 0.77-1.03]). Patients in the dialysis group had a higher rate of intensive care unit admissions per 1000 hospitalizations (98.37 [95% CI, 81.09-115.65] vs 54.51 [95% CI, 37.76-71.26]; IRR, 1.80 [95% CI, 1.28-2.54]) and lower rates of inpatient palliative care per 1000 in-hospital days (3.92 [95% CI, 3.13-4.72] vs 8.60 [95% CI, 6.3-11.0]; IRR, 0.45 [95% CI, 0.32-0.64]). Conclusions and Relevance: In this cohort study, compared with nondialysis care, patients who received maintenance dialysis spent more time in the hospital and were more likely to be admitted to intensive care units. This finding suggests trade-offs between longer survival and higher intensity of use of health care services as a function of dialysis initiation. Maintenance dialysis may be a proxy for the type of philosophy of care driving increased in-hospital time and intensive care and less use of palliative care.

5.
Perit Dial Int ; 40(2): 185-192, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32063191

RESUMO

BACKGROUND: Peritoneal dialysis (PD) is a more cost-effective therapy to treat kidney failure than in-center hemodialysis, but successful therapy requires a functioning PD catheter that causes minimal complications. In 2015, the North American Chapter of the International Society for Peritoneal Dialysis established the North American PD Catheter Registry to improve practices and patient outcomes following PD catheter insertion. AIMS: The objective of this study is to propose a methodology for defining insertion-related complications that lead to significant adverse events and report the risk of these complications among patients undergoing laparoscopic PD catheter insertion. METHODS: Patients undergoing laparoscopic PD catheter insertion were enrolled at 14 participating centers in Canada and the United States and followed using a Web-based registry. Insertion-related complications were defined as flow restriction, exit-site leak, or abdominal pain at any point during follow-up. We also included infections or bleeding within 30 days of insertion, and any immediate postoperative complications. Adverse events were categorized as PD never starting or termination of PD therapy, delay in the start of PD therapy or interruption of PD therapy, an emergency department visit or hospitalization, or need for invasive procedures. Cause-specific cumulative incidence functions were used to estimate risk. RESULTS: Five hundred patients underwent laparoscopic PD catheter insertion between 10 November 2015 and 24 July 2018. The cumulative risk of insertion-related complications 6 months from the date of insertion that led to an adverse event was 24%. The risk of flow restriction, exit-site leak, and pain at 6 months was 10.2%, 5.7%, and 5.3%, respectively. PD was never started or terminated in 6.4% of patients due to an insertion-related complication. Leaks and flow restrictions were most likely to delay or interrupt PD therapy. Flow restrictions were the primary cause of invasive procedures. Fifty percent of the complications occurred before the start of PD therapy. CONCLUSIONS: Insertion-related complications leading to significant adverse events following laparoscopic placement of PD catheters are common. Many complications occur before the start of PD. Insertion-related complications are an important area of focus for future research and quality improvement efforts.

6.
J Am Soc Nephrol ; 31(3): 591-601, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32024663

RESUMO

BACKGROUND: Urine albumin-to-creatinine ratio (ACR) and protein-to-creatinine ratio (PCR) are used to measure urine protein. Recent guidelines endorse ACR use, and equations have been developed incorporating ACR to predict risk of kidney failure. For situations in which PCR only is available, having a method to estimate ACR from PCR as accurately as possible would be useful. METHODS: We used data from a population-based cohort of 47,714 adults in Alberta, Canada, who had simultaneous assessments of urine ACR and PCR. After log-transforming ACR and PCR, we used cubic splines and quantile regression to estimate the median ACR from a PCR, allowing for modification by specified covariates. On the basis of the cubic splines, we created models using linear splines to develop equations to estimate ACR from PCR. In a subcohort with eGFR<60 ml/min per 1.73 m2, we then used the kidney failure risk equation to compare kidney failure risk using measured ACR as well as estimated ACR that had been derived from PCR. RESULTS: We found a nonlinear association between log(ACR) and log(PCR), with the implied albumin-to-protein ratio increasing from <30% in normal to mild proteinuria to about 70% in severe proteinuria, and with wider prediction intervals at lower levels. Sex was the most important modifier of the relationship between ACR and PCR, with men generally having a higher albumin-to-protein ratio. Estimates of kidney failure risk were similar using measured ACR and ACR estimated from PCR. CONCLUSIONS: We developed equations to estimate the median ACR from a PCR, optionally including specified covariates. These equations may prove useful in certain retrospective clinical or research applications where only PCR is available.

8.
Vet Surg ; 49(1): 53-60, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332797

RESUMO

OBJECTIVE: To determine the incidence of and risk factors for regurgitation in dogs within 24 hours of surgical management of brachycephalic obstructive airway syndrome (BOAS). STUDY DESIGN: Retrospective single center study of dogs undergoing BOAS surgery over four years (2013-2017). ANIMALS: Two hundred fifty-eight client-owned dogs referred for surgical intervention for BOAS. METHODS: Electronic medical records were searched for dogs that had undergone surgery for BOAS at a UK specialist referral hospital. Data were assessed by using univariable binomial logistic regression; confounding factors were then identified in a multivariable model. RESULTS: There was an increase in the proportion of dogs that regurgitated while hospitalized preoperatively vs during the first 24 hours postoperatively, from 28 (10.9%) to 89 (34.5%), respectively (P < .0001). History of regurgitation (P = .017, odds ratio [OR] 2.539, 95% confidence interval [CI] 1.178-5.469) and age (P = .008, OR 0.712, 95% CI 0.553-0.916) were detected as risk factors for postoperative regurgitation. For every 1-year increase in age, the odds of experiencing postoperative regurgitation were reduced by 28.8%. CONCLUSION: Corrective surgery for BOAS was associated with a marked incidence of postoperative regurgitation. Younger dogs and those with a history of regurgitation were predisposed to postoperative regurgitation. CLINICAL SIGNIFICANCE: The increased frequency of regurgitation after surgical treatment of BOAS, especially in younger dogs, provides justification for counseling owners regarding this postoperative complication.

9.
Food Chem ; 302: 125290, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31404873

RESUMO

In our daily lives, we consume foods that have been transported, stored, prepared, cooked, or otherwise processed by ourselves or others. Food storage and preparation have drastic effects on the chemical composition of foods. Untargeted mass spectrometry analysis of food samples has the potential to increase our chemical understanding of these processes by detecting a broad spectrum of chemicals. We performed a time-based analysis of the chemical changes in foods during common preparations, such as fermentation, brewing, and ripening, using untargeted mass spectrometry and molecular networking. The data analysis workflow presented implements an approach to study changes in food chemistry that can reveal global alterations in chemical profiles, identify changes in abundance, as well as identify specific chemicals and their transformation products. The data generated in this study are publicly available, enabling the replication and re-analysis of these data in isolation, and serve as a baseline dataset for future investigations.


Assuntos
Bebidas/análise , Análise de Alimentos , Manipulação de Alimentos , Espectrometria de Massas , Metabolômica , Fermentação , Fluxo de Trabalho
10.
Can J Kidney Health Dis ; 6: 2054358119861943, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798925

RESUMO

Background: Clinical practice guidelines recommend arteriovenous fistulas as the preferred form of vascular access for hemodialysis. However, some studies have suggested that older age is associated with poorer fistula outcomes. Objective: We assessed the impact of age on the outcomes of fistula creation and access-related procedures. Design: This was a prospective cohort study using data collected as part of the Dialysis Measurement Analysis and Reporting (DMAR) system. Setting: Participating Canadian dialysis programs, including Southern Alberta Renal Program, Manitoba Renal Program, Sunnybrook Health Sciences Centre (Toronto, Ontario), London Health Sciences Centre (London, Ontario), and The Ottawa Hospital (Ottawa, Ontario). Patients: Incident hemodialysis patients aged 18 years and older who started dialysis between January 1, 2004, and May 31, 2012. Measurements: The primary outcome was the proportion of all first fistula attempts that resulted in catheter-free fistula use, defined as independent use of a fistula for hemodialysis (ie, no catheter in place). Secondary outcomes included the time to catheter-free fistula use among patients with a fistula creation attempt, total number of days of catheter-free fistula use, and the proportion of a patient's hemodialysis career spent with an independently functioning fistula (ie, catheter-free fistula use). Methods: We compared patient characteristics by age group, using t tests or Wilcoxon rank sum tests, and chi-square or Fisher exact tests, as appropriate. Logistic and fractional logistic regression were used to estimate the odds of achieving catheter-free fistula use by age group and the proportion of dialysis time spent catheter-free, respectively. Results: A total of 1091 patients met our inclusion criteria (567 age ≥ 65; 524 age < 65). Only 57% of first fistula attempts resulted in catheter-free fistula use irrespective of age (adjusted odds ratio [OR]≥65vs<65: 1.01; P = .93). The median time from hemodialysis start to catheter-free use of the first fistula did not differ by age when grouped into fistulas attempted pre- and post-dialysis initiation. The adjusted rates of access-related procedures were comparable (incidence rate ratio [IRR]≥65vs<65: 0.95; P = .32). The median percentage of follow-up time spent catheter-free was similar and low in patients who attempted fistulas (<65 years: 19% vs ≥65 years: 21%; P = .85). Limitations: The relatively short follow-up time may have underestimated the benefits of fistula creation and the observational study design precludes inferences about causality. Conclusions: In our study, older patients who underwent a fistula attempt were just as likely as younger patients to achieve catheter-free fistula use, within a similar time frame, and while requiring a similar number of access procedures. However, the minority of dialysis time was spent catheter-free.

11.
J Bone Miner Res ; 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31886921

RESUMO

Glucocorticoids (GCs) are potent immune-modulating drugs with significant side effects, including glucocorticoid-induced osteoporosis (GIO). GCs directly induce osteoblast and osteocyte apoptosis but also alter intestinal microbiota composition. Although the gut microbiota is known to contribute to the regulation of bone density, its role in GIO has never been examined. To test this, male C57/Bl6J mice were treated for 8 weeks with GC (prednisolone, GC-Tx) in the presence or absence of broad-spectrum antibiotic treatment (ABX) to deplete the microbiota. Long-term ABX prevented GC-Tx-induced trabecular bone loss, showing the requirement of gut microbiota for GIO. Treatment of GC-Tx mice with a probiotic (Lactobacillus reuteri [LR]) prevented trabecular bone loss. Microbiota analyses indicated that GC-Tx changed the abundance of Verrucomicobiales and Bacteriodales phyla and random forest analyses indicated significant differences in abundance of Porphyromonadaceae and Clostridiales operational taxonomic units (OTUs) between groups. Furthermore, transplantation of GC-Tx mouse fecal material into recipient naïve, untreated WT mice caused bone loss, supporting a functional role for microbiota in GIO. We also report that GC caused intestinal barrier breaks, as evidenced by increased serum endotoxin level (2.4-fold), that were prevented by LR and ABX treatments. Enhancement of barrier function with a mucus supplement prevented both GC-Tx-induced barrier leakage and trabecular GIO. In bone, treatment with ABX, LR or a mucus supplement reduced GC-Tx-induced osteoblast and osteocyte apoptosis. GC-Tx suppression of Wnt10b in bone was restored by the LR and high-molecular-weight polymer (MDY) treatments as well as microbiota depletion. Finally, we identified that bone-specific Wnt10b overexpression prevented GIO. Taken together, our data highlight the previously unappreciated involvement of the gut microbiota and intestinal barrier function in trabecular GIO pathogenesis (including Wnt10b suppression and osteoblast and osteocyte apoptosis) and identify the gut as a novel therapeutic target for preventing GIO. © 2019 American Society for Bone and Mineral Research.

12.
Wilderness Environ Med ; 30(4S): S87-S99, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31780084

RESUMO

The Wilderness Medical Society reconvened an expert panel to update best practice guidelines for spinal cord protection during trauma management. This panel, with membership updated in 2018, was charged with the development of evidence-based guidelines for management of the injured or potentially injured spine in wilderness environments. Recommendations are made regarding several parameters related to spinal cord protection. These recommendations are graded based on the quality of supporting evidence and balance the benefits and risks/burdens for each parameter according to the methodology stipulated by the American College of Chest Physicians. Key recommendations include the concept that interventions should be goal oriented (spinal cord/column protection in the context of overall patient and provider safety) rather than technique oriented (immobilization). This evidence-based, goal-oriented approach does not support the immobilization of suspected spinal injuries via rigid collars or backboards.


Assuntos
Padrões de Prática Médica , Traumatismos da Medula Espinal/terapia , Traumatismos da Coluna Vertebral/terapia , Medicina Selvagem/normas , Humanos , Imobilização/efeitos adversos , Imobilização/métodos , Sociedades Médicas , Traumatismos da Medula Espinal/prevenção & controle , Traumatismos da Coluna Vertebral/prevenção & controle , Medicina Selvagem/métodos
13.
Genome Biol ; 20(1): 226, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672156

RESUMO

As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewer samples. We term this approach leaderboard metagenome sequencing. To explore protocol optimization for leaderboard metagenomics in real samples, we introduce a benchmark of library prep and sequencing using internal references generated by synthetic long-read technology, allowing us to evaluate high-throughput library preparation methods against gold-standard reference genomes derived from the samples themselves. We introduce a low-cost protocol for high-throughput library preparation and sequencing.


Assuntos
Biblioteca Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica/métodos , Animais , Benchmarking , Microbioma Gastrointestinal , Humanos , Camundongos
14.
Nat Methods ; 16(12): 1306-1314, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31686038

RESUMO

Integrating multiomics datasets is critical for microbiome research; however, inferring interactions across omics datasets has multiple statistical challenges. We solve this problem by using neural networks (https://github.com/biocore/mmvec) to estimate the conditional probability that each molecule is present given the presence of a specific microorganism. We show with known environmental (desert soil biocrust wetting) and clinical (cystic fibrosis lung) examples, our ability to recover microbe-metabolite relationships, and demonstrate how the method can discover relationships between microbially produced metabolites and inflammatory bowel disease.


Assuntos
Bactérias/metabolismo , Microbiota , Animais , Benchmarking , Cianobactérias/metabolismo , Fibrose Cística/microbiologia , Doenças Inflamatórias Intestinais/microbiologia , Camundongos , Pseudomonas aeruginosa/metabolismo
15.
mSystems ; 4(5)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551401

RESUMO

To visualize the personalized distributions of pathogens and chemical environments, including microbial metabolites, pharmaceuticals, and their metabolic products, within and between human lungs afflicted with cystic fibrosis (CF), we generated three-dimensional (3D) microbiome and metabolome maps of six explanted lungs from three cystic fibrosis patients. These 3D spatial maps revealed that the chemical environments differ between patients and within the lungs of each patient. Although the microbial ecosystems of the patients were defined by the dominant pathogen, their chemical diversity was not. Additionally, the chemical diversity between locales in the lungs of the same individual sometimes exceeded interindividual variation. Thus, the chemistry and microbiome of the explanted lungs appear to be not only personalized but also regiospecific. Previously undescribed analogs of microbial quinolones and antibiotic metabolites were also detected. Furthermore, mapping the chemical and microbial distributions allowed visualization of microbial community interactions, such as increased production of quorum sensing quinolones in locations where Pseudomonas was in contact with Staphylococcus and Granulicatella, consistent with in vitro observations of bacteria isolated from these patients. Visualization of microbe-metabolite associations within a host organ in early-stage CF disease in animal models will help elucidate the complex interplay between the presence of a given microbial structure, antibiotics, metabolism of antibiotics, microbial virulence factors, and host responses.IMPORTANCE Microbial infections are now recognized to be polymicrobial and personalized in nature. Comprehensive analysis and understanding of the factors underlying the polymicrobial and personalized nature of infections remain limited, especially in the context of the host. By visualizing microbiomes and metabolomes of diseased human lungs, we reveal how different the chemical environments are between hosts that are dominated by the same pathogen and how community interactions shape the chemical environment or vice versa. We highlight that three-dimensional organ mapping methods represent hypothesis-building tools that allow us to design mechanistic studies aimed at addressing microbial responses to other microbes, the host, and pharmaceutical drugs.

16.
J Am Soc Nephrol ; 30(11): 2219-2227, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31540963

RESUMO

BACKGROUND: Most kidney failure risk calculators are based on methods that censor for death. Because mortality is high in people with severe, nondialysis-dependent CKD, censoring for death may overestimate their risk of kidney failure. METHODS: Using 2002-2014 population-based laboratory and administrative data for adults with stage 4 CKD in Alberta, Canada, we analyzed the time to the earliest of kidney failure, death, or censoring, using methods that censor for death and methods that treat death as a competing event factoring in age, sex, diabetes, cardiovascular disease, eGFR, and albuminuria. Stage 4 CKD was defined as a sustained eGFR of 15-30 ml/min per 1.73 m2. RESULTS: Of the 30,801 participants (106,447 patient-years at risk; mean age 77 years), 18% developed kidney failure and 53% died. The observed risk of the combined end point of death or kidney failure was 64% at 5 years and 87% at 10 years. By comparison, standard risk calculators that censored for death estimated these risks to be 76% at 5 years and >100% at 7.5 years. Censoring for death increasingly overestimated the risk of kidney failure over time from 7% at 5 years to 19% at 10 years, especially in people at higher risk of death. For example, the overestimation of 5-year absolute risk ranged from 1% in a woman without diabetes, cardiovascular disease, or albuminuria and with an eGFR of 25 ml/min per 1.73 m2 (9% versus 8%), to 27% in a man with diabetes, cardiovascular disease, albuminuria >300 mg/d, and an eGFR of 20 ml/min per 1.73 m2 (78% versus 51%). CONCLUSIONS: Kidney failure risk calculators should account for death as a competing risk to increase their accuracy and utility for patients and providers.

17.
Metabolites ; 9(8)2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31405168

RESUMO

Fermenting food is an ancient form of preservation ingrained many in human societies around the world. Westernized diets have moved away from such practices, but even in these cultures, fermented foods are seeing a resurgent interested due to their believed health benefits. Here, we analyze the microbiome and metabolome of organically fermented vegetables, using a salt brine, which is a common 'at-home' method of food fermentation. We found that the natural microbial fermentation had a strong effect on the food metabolites, where all four foods (beet, carrot, peppers and radishes) changed through time, with a peak in molecular diversity after 2-3 days and a decrease in diversity during the final stages of the 4-day process. The microbiome of all foods showed a stark transition from one that resembled a soil community to one dominated by Enterobacteriaceae, such as Erwinia spp., within a single day of fermentation and increasing amounts of Lactobacillales through the fermentation process. With particular attention to plant natural products, we observed significant transformations of polyphenols, triterpenoids and anthocyanins, but the degree of this metabolism depended on the food type. Beets, radishes and peppers saw an increase in the abundance of these compounds as the fermentation proceeded, but carrots saw a decrease through time. This study showed that organically fermenting vegetables markedly changed their chemistry and microbiology but resulted in high abundance of Enterobacteriaceae which are not normally considered as probiotics. The release of beneficial plant specialized metabolites was observed, but this depended on the fermented vegetable.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31369099

RESUMO

BACKGROUND: Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes. METHOD: Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7-9 being critically important). The relative importance was determined by a best-worst scale using multinomial logistic regression. Open text responses were analysed thematically. RESULTS: The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best-worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best-worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle. CONCLUSIONS: Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD.

19.
Can J Kidney Health Dis ; 6: 2054358119843139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105964

RESUMO

Background: Fistula creation is recommended to avoid the use of central venous catheters for hemodialysis. The extent to which timing of fistula creation minimizes catheter use is unclear. Objective: To compare patient outcomes of 2 fistula creation strategies: fistula attempt prior to the initiation of dialysis ("predialysis") or fistula attempt after starting dialysis ("postinitiation"). Design: Cohort study. Setting: Five Canadian dialysis programs. Patients: Patients who started hemodialysis between 2004 and 2012, who underwent fistula creation, and were tracked in the Dialysis Measurement Analysis and Reporting (DMAR) system. Measurements: Catheter-free fistula use within 1 year of hemodialysis start, probability of catheter-free fistula use during follow-up, and rates of access-related procedures. Methods: Retrospective data analysis: logistic regression; negative binomial regression. Results: Five hundred and eight patients had fistula attempts predialysis and 583 postinitiation. At 1 year, 80% of those with predialysis attempts achieved catheter-free use compared to 45% with post-initiation attempts (adjusted odds ratio [OR]preVSpost = 4.67; 95% confidence interval [CI] = 3.28-6.66). The average of all patient follow-up time spent catheter-free was 63% and 28%, respectively (probability of use per unit time, ORpreVSpost = 2.90; 95% CI = 2.18-3.85). This finding was attenuated when accounting for maturation time and when restricting the analysis to those who achieved catheter-free use. Predialysis fistula attempts were associated with lower procedure rates after dialysis initiation-1.61 procedures per person-year compared with 2.55-but had 0.65 more procedures per person prior to starting dialysis. Limitations: Observational design, unknown indication for predialysis and postinitiation fistula creation, and unknown reasons for prolonged catheter use. Conclusions: Predialysis fistula attempts were associated with a higher probability of catheter-free use and remaining catheter-free over time, and also resulted in fewer procedures compared with postinitiation attempts, which could be due to timing of attempt or patient factors. Catheter use and procedures were still common for all patients, regardless of the timing of fistula creation.

20.
mBio ; 10(2)2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992350

RESUMO

Pulmonary exacerbations are the leading cause of death in cystic fibrosis (CF) patients. To track microbial dynamics during acute exacerbations, a CF rapid response (CFRR) strategy was developed. The CFRR relies on viromics, metagenomics, metatranscriptomics, and metabolomics data to rapidly monitor active members of the viral and microbial community during acute CF exacerbations. To highlight CFRR, a case study of a CF patient is presented, in which an abrupt decline in lung function characterized a fatal exacerbation. The microbial community in the patient's lungs was closely monitored through the multi-omics strategy, which led to the identification of pathogenic shigatoxigenic Escherichia coli (STEC) expressing Shiga toxin. This case study illustrates the potential for the CFRR to deconstruct complicated disease dynamics and provide clinicians with alternative treatments to improve the outcomes of pulmonary exacerbations and expand the life spans of individuals with CF.IMPORTANCE Proper management of polymicrobial infections in patients with cystic fibrosis (CF) has extended their life span. Information about the composition and dynamics of each patient's microbial community aids in the selection of appropriate treatment of pulmonary exacerbations. We propose the cystic fibrosis rapid response (CFRR) as a fast approach to determine viral and microbial community composition and activity during CF pulmonary exacerbations. The CFRR potential is illustrated with a case study in which a cystic fibrosis fatal exacerbation was characterized by the presence of shigatoxigenic Escherichia coli The incorporation of the CFRR within the CF clinic could increase the life span and quality of life of CF patients.


Assuntos
Fibrose Cística/complicações , Progressão da Doença , Infecções por Escherichia coli/diagnóstico , Genômica , Pulmão/microbiologia , Metabolômica , Adulto , Estudos de Casos e Controles , Coinfecção/complicações , Fibrose Cística/microbiologia , Gerenciamento Clínico , Evolução Fatal , Perfilação da Expressão Gênica , Humanos , Pulmão/fisiopatologia , Masculino , Metaboloma , Metagenoma , Microbiota , Toxina Shiga/genética , Escherichia coli Shiga Toxigênica/genética , Escherichia coli Shiga Toxigênica/patogenicidade
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