Peritoneal Effluent Cell-Free DNA Sequencing in Peritoneal Dialysis Patients With and Without Peritonitis.

RATIONALE & OBJECTIVE: Conventional culture can be insensitive for the detection of rare infections and for the detection of common infections in the setting of recent antibiotic usage. Patients receiving peritoneal dialysis (PD) with suspected peritonitis have a significant proportion of negative conventional cultures. This study examines the utility of metagenomic sequencing of peritoneal effluent cell-free DNA (cfDNA) for evaluating the peritoneal effluent in PD patients with and without peritonitis. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We prospectively characterized cfDNA in 68 peritoneal effluent samples obtained from 33 patients receiving PD at a single center from September 2016 to July 2018. OUTCOMES: Peritoneal effluent, microbial, and human cfDNA characteristics were evaluated in culture-confirmed peritonitis and culture-negative peritonitis. ANALYTICAL APPROACH: Descriptive statistics were analyzed and microbial cfDNA was detected in culture-confirmed peritonitis and culture-negative peritonitis. RESULTS: Metagenomic sequencing of cfDNA was able to detect and identify bacterial, viral, and eukaryotic pathogens in the peritoneal effluent from PD patients with culture-confirmed peritonitis, as well as patients with recent antibiotic usage and in cases of culture-negative peritonitis. LIMITATIONS: Parallel cultures were not obtained in all the peritoneal effluent specimens. CONCLUSIONS: Metagenomic cfDNA sequencing of the peritoneal effluent can identify pathogens in PD patients with peritonitis, including culture-negative peritonitis.

Gut microbiota profiles and fecal beta-glucuronidase activity in kidney transplant recipients with and without post-transplant diarrhea.

Post-transplant diarrhea is a common complication after solid organ transplantation and is frequently attributed to the widely prescribed immunosuppressant mycophenolate mofetil (MMF). Given recent work identifying the relationship between MMF toxicity and gut bacterial ß-glucuronidase activity, we evaluated the relationship between gut microbiota composition, fecal ß-glucuronidase activity, and post-transplant diarrhea. We recruited 97 kidney transplant recipients and profiled the gut microbiota in 273 fecal specimens using 16S rRNA gene sequencing. We further characterized fecal ß-glucuronidase activity in a subset of this cohort. Kidney transplant recipients with post-transplant diarrhea had decreased gut microbial diversity and decreased relative gut abundances of 12 genera when compared to those without post-transplant diarrhea (adjusted p value < .15, Wilcoxon rank sum test). Among the kidney transplant recipients with post-transplant diarrhea, those with higher fecal ß-glucuronidase activity had a more prolonged course of diarrhea (≥7 days) compared to patients with lower fecal ß-glucuronidase activity (91% vs 40%, p = .02, Fisher's exact test). Our data reveal post-transplant diarrhea as a complex phenomenon with decreased gut microbial diversity and commensal gut organisms. This study further links commensal bacterial metabolism with an important clinical outcome measure, suggesting fecal ß-glucuronidase activity could be a novel biomarker for gastrointestinal-related MMF toxicity.

Kidney recipients with allograft failure, transition of kidney care (KRAFT): A survey of contemporary practices of transplant providers.

Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first. More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care.

COVID-19 infection in former living kidney donors.

The COVID-19 pandemic brought living donor kidney transplant programs across the United States to a near halt in March 2020. As programs have begun to reopen, potential donor candidates often inquire about their risk of a COVID-19 infection and its potential impact on kidney function after donation. To address their concerns, we surveyed 1740 former live kidney donors at four transplant centers located in New York and Michigan. Of these, 839 (48.2%) donors responded, their mean age was 46 ± 12.5 years, 543 (65%) were females, and 611 (73%) were white. Ninety-two donors (11%) had symptoms suggestive of a COVID-19 infection with fever (48%) and fatigue (43%) being the most common. Among those with symptoms, 42 donors underwent testing and 16 tested positive. Testing was more common among donors with private insurance, and a positive test result was more common among young black donors. Only one donor surveyed required hospitalization and none required dialysis. Fourteen donors have recovered completely and two partially. Our survey highlights that a COVID-19 infection in former donors results in a mild disease with good recovery. These data will be useful for transplant programs to counsel living donors who are considering kidney donation during this pandemic.

Gut commensal microbiota and decreased risk for Enterobacteriaceae bacteriuria and urinary tract infection.

Urinary tract infection (UTI) is a common complication in kidney transplant recipients and can lead to significant morbidity and mortality. Recent evidence supports a role for the gut as a source for UTIs but little is known about the relationship between gut commensal bacteria and UTI development. We hypothesized that the abundance of gut commensal bacteria is associated with a lower risk of developing bacteriuria and UTIs. We performed gut microbiome profiling using 16S rRNA gene sequencing of the V4-V5 hypervariable region on 510 fecal specimens in 168 kidney transplant recipients. Fifty-one kidney transplant recipients (30%) developed Enterobacteriaceae bacteriuria within the first 6 months after transplantation (Enterobacteriaceae Bacteriuria Group) and 117 did not (No Enterobacteriaceae Bacteriuria Group). The relative abundances of Faecalibacterium and Romboutsia were significantly higher in the fecal specimens from the No Enterobacteriaceae Bacteriuria Group than those from the Enterobacteriaceae Bacteriuria Group (Adjusted P value<.01). The combined relative abundance of Faecalibacterium and Romboutsia was inversely correlated with the relative abundance of Enterobacteriaceae (r = -0.13, P = .003). In a multivariable Cox Regression, a top tercile cutoff of the combined relative abundance of Faecalibacterium and Romboutsia of ≥13.7% was independently associated with a decreased risk for Enterobacteriaceae bacteriuria (hazard ratio 0.3, P = .02) and Enterobacteriaceae UTI (hazard ratio 0.4, P = .09). In conclusion, we identify bacterial taxa associated with decreased risk for Enterobacteriaceae bacteriuria and Enterobacteriaceae UTI in kidney transplant recipients, which supports future studies on modulating the gut microbiota as a novel treatment for preventing UTIs.

Impact of gender and race on expectations and outcomes in total knee arthroplasty.

BACKGROUND: Total joint arthroplasty is one of the most common surgeries performed in the United States with total knee arthroplasty (TKA) being one of the most successful surgeries for restoring function and diminishing pain. Even with the demonstrated success of TKA and a higher prevalence of arthritis and arthritis related disability among minorities, racial and gender disparity remains a constant issue in providing care for the adult reconstruction patient. AIM: To assess the role of demographics and expectations on differences in perioperative patient reported outcomes (PRO) following TKA. METHODS: One hundred and thirty-three patients scheduled for primary unilateral TKA secondary to moderate to severe osteoarthritis were enrolled in this two-institution prospective study. Validated PRO questionnaires were collected at four time points. Statistical analysis was conducted to determine the impact of gender, ethnic background and expectation surveys responses to assess PRO at these time points. RESULTS: Females were associated with worse preoperative Knee Injury and Osteoarthritis Outcome Scores (KOOS) for symptoms, pain, and activities of daily living. African Americans were associated with worse KOOS for pain, activities of daily living, and quality of life. Despite worse preoperative scores, no difference was noted in these categories between the groups postoperatively. Additionally, all pre-operative psychometric scales were equivalent across groups except Geriatric Depression scale, which was significantly different between groups within the Race and Age Group (P < 0.05). Conversely, Pain Catastrophizing Scale, was significantly different for all subscales and total score within Age Group (P < 0.05), and the Magnification, Helplessness subscales as well as the Total score were significantly different between groups for Race and Relationship Status (P < 0.01). CONCLUSION: We conclude that female and African American patients have lower preoperative KOOS scores compared to white male patients. No postoperative differences in outcomes between these groups.

Gut uropathogen abundance is a risk factor for development of bacteriuria and urinary tract infection.

The origin of most bacterial infections in the urinary tract is often presumed to be the gut. Herein, we investigate the relationship between the gut microbiota and future development of bacteriuria and urinary tract infection (UTI). We perform gut microbial profiling using 16S rRNA gene deep sequencing on 510 fecal specimens from 168 kidney transplant recipients and metagenomic sequencing on a subset of fecal specimens and urine supernatant specimens. We report that a 1% relative gut abundance of Escherichia is an independent risk factor for Escherichia bacteriuria and UTI and a 1% relative gut abundance of Enterococcus is an independent risk factor for Enterococcus bacteriuria. Strain analysis establishes a close strain level alignment between species found in the gut and in the urine in the same subjects. Our results support a gut microbiota-UTI axis, suggesting that modulating the gut microbiota may be a potential novel strategy to prevent UTIs.

Butyrate-producing gut bacteria and viral infections in kidney transplant recipients: A pilot study.

BACKGROUND: The gut microbiome is being associated increasingly with development of infections besides Clostridium difficile infection. A recent study found an association between butyrate-producing gut (BPG) bacteria and less frequent development of lower respiratory viral infections in allogeneic hematopoietic stem cell transplant recipients (Haak et al, Blood 131(26): 2978, 2018). In this investigation, we examine the relationship between the abundance of BPG bacteria and the development of viral infections in a cohort of kidney transplant recipients. METHODS: We recruited 168 kidney transplant recipients who provided 510 fecal specimens in the first 3 months after transplantation and profiled the gut microbiota using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We classified the kidney transplant recipients into higher BPG Bacteria Group and lower BPG Bacteria Group using the same criteria of 1% relative gut abundance of BPG bacteria as the Haak et al study. RESULTS: Administration of antibiotics against anaerobes was associated with a significant decrease in the relative gut abundance of BPG bacteria. The higher BPG Bacteria Group was associated with less development of respiratory viral infections (Hazard Ratio [HR]: 0.28, P = .01) but not with less development of CMV viremia (HR: 0.38, P = .13) or BK viremia (HR: 1.02, P = .98) at 2 years post transplantation. CONCLUSION: Our pilot investigation supports future validation of the relationship between high relative gut abundance of BPG bacteria and decreased risk for development of respiratory viral infections.

Gastrointestinal pathogen colonization and the microbiome in asymptomatic kidney transplant recipients.

BACKGROUND: In kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of GI pathogens in asymptomatic individuals in this population. METHODS: We recruited 142 kidney transplant recipients who provided a non-diarrheal fecal sample within the first 10 days after transplantation. The specimens were evaluated for GI pathogens using the BioFire® FilmArray® GI Panel (BioFire Diagnostics, LLC), which tests for 22 pathogens. The fecal microbiome was also characterized using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We evaluated whether detection of Clostridioides difficile and other GI pathogens was associated with post-transplant diarrhea within the first 3 months after transplantation. RESULTS: Among the 142 subjects, a potential pathogen was detected in 43 (30%) using the GI Panel. The most common organisms detected were C difficile (n = 24, 17%), enteropathogenic Escherichia coli (n = 8, 6%), and norovirus (n = 5, 4%). Detection of a pathogen on the GI panel or detection of C difficile alone was not associated with future post-transplant diarrhea (P > .05). The estimated number of gut bacterial species was significantly lower in subjects colonized with C difficile than those not colonized with a GI pathogen (P = .01). CONCLUSION: Colonization with GI pathogens, particularly C difficile, is common at the time of kidney transplantation but does not predict subsequent diarrhea. Detection of C difficile carriage was associated with decreased microbial diversity and may be a biomarker of gut dysbiosis.

Gut microbiota dysbiosis and diarrhea in kidney transplant recipients.

Posttransplant diarrhea is associated with kidney allograft failure and death, but its etiology remains unknown in the majority of cases. Because altered gut microbial ecology is a potential basis for diarrhea, we investigated whether posttransplant diarrhea is associated with gut dysbiosis. We enrolled 71 kidney allograft recipients for serial fecal specimen collections in the first 3 months of transplantation and profiled the gut microbiota using 16S ribosomal RNA (rRNA) gene V4-V5 deep sequencing. The Shannon diversity index was significantly lower in 28 diarrheal fecal specimens from 25 recipients with posttransplant diarrhea than in 112 fecal specimens from 46 recipients without posttransplant diarrhea. We found a lower relative abundance of 13 commensal genera (Benjamini-Hochberg adjusted P ≤ .15) in the diarrheal fecal specimens including the same 4 genera identified in our prior study. The 28 diarrheal fecal specimens were also evaluated by a multiplexed polymerase chain reaction (PCR) assay for 22 bacterial, viral, and protozoan gastrointestinal pathogens, and 26 specimens were negative for infectious etiologies. Using PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) to predict metagenomic functions, we found that diarrheal fecal specimens had a lower abundance of metabolic genes. Our findings suggest that posttransplant diarrhea is not associated with common infectious diarrheal pathogens but with a gut dysbiosis.

The Effect of Psychosensory Therapy on Short-term Outcomes of Total Joint Arthroplasty: A Randomized Controlled Trial.

Poor outcomes associated with increased perioperative opioid use have led investigators to seek alternative pain management modalities after total joint arthroplasty. Nonpharmacological approaches, such as electroceuticals, have shown promise. The purpose of this study was to evaluate the effects of "havening," a specific form of psychosensory therapy, on postoperative pain scores and narcotic consumption. In this prospective, randomized controlled trial, the authors compared 19 patients who underwent psychosensory therapy with 22 patients who served as the control group. Visual analog scale scores were collected preoperatively, every day during the hospitalization, and at approximately 1-month follow-up. Narcotic consumption during hospitalization was converted into daily morphine milligram equivalents and compared between the cohorts. In addition, postoperative complications, emergency department visits, and readmissions were compared between the cohorts. No difference in visual analog scale pain scores was reported between cohorts on postoperative day 1 (P=.229), at discharge (P=.434), or at 1-month follow-up (P=.256). Furthermore, there was no significant variance in mean daily morphine milligram equivalents (P=.221), length of stay (P=.313), postoperative complications (P=.255), 90-day readmissions (P=.915), and emergency department visits (P=.46) between the cohorts. This study showed that psychosensory therapy was not effective in reducing pain or narcotic consumption following total joint arthroplasty. Nonetheless, future studies assessing the role of psychosensory therapeutic interventions among patients after total joint arthroplasty are warranted to better understand the clinical implications of innovative therapies aimed at alleviating pain. [Orthopedics. 2018; 41(6):e848-e853.].

Prevalence of Neurocognitive Dysfunction and Its Effects on Postoperative Outcomes in Total Joint Arthroplasty.

BACKGROUND: The prevalence of neurocognitive dysfunction (NCD) and its effects on postoperative outcomes have not been well characterized following total joint arthroplasty (TJA) population. This study aims at better understand this relationship. METHODS: Patients were evaluated for neurocognitive function using the grooved pegboard test for the dominant (PEG-D) and nondominant hand (PEG-N), and the Rey Auditory Verbal Learning Test (RAVLT). The patient scores for each test was compared to age-controlled normative values in order to identify NCD. Baseline characteristics and postoperative outcomes were then compared amongst the two cohorts. RESULTS: Ninety-nine consecutive patients were prospectively enrolled. Nearly 54% were identified as neurocognitively deficient on at least 1 of the 3 tests (31% by RAVLT, 21% by PEG-D, and 30% by PEG-N). There was a statistically significant prevalence of NCD in patients older than 60 years when compared to normative controls for RAVLT (P < .001). Patients with depression or an American Society of Anesthesiologist score of 3 were 5 times as likely to have NCD, while patients with a body mass index between 20-30 kg/m2 were 5 times less likely to have NCD. Furthermore, patients identified as NCD preoperatively were significantly more likely to be transferred to the intensive care unit (48% vs 14%) and fail physical therapy (64% vs 17%), respectively. CONCLUSION: NCD is highly prevalent within total joint arthroplasty candidates and may be correlated with higher body mass index, American Society of Anesthesiologist scores, and rates of depression. The condition predisposes patients to suboptimal postoperative outcomes including increased intensive care unit admissions and prolonged rehabilitation.

Impact of Social Support and Pain Coping Abilityon Length of Stay and Discharge Disposition following Hip and Knee Arthroplasty A Prospective Study.

INTRODUCTION: While there are many factors known to predict the outcomes of hip and knee arthroplasty procedures, there is a growing interest in predictors that take into consideration the social and psychological preparedness of patients prior to surgery. This study's aim was to determine whether patients' preoperative social support and pain catastrophizing characteristics are independently associated with the outcomes of postoperative length of stay or discharge disposition following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: Data on a prospective sample of 189 THA and TKA adult patients using the pain catastrophizing scale and the medical outcomes study social support expectation score were analyzed. Demographic characteristics, such as age, gender, and race (Caucasian versus non-Caucasian), which served as covariates, were also collected. Bivariate associations between our outcome variables and covariates using Pearson's and Spearman's rank correlation coefficients and Mann Whitney U test for continuous variables (age, MOS-SSS) and Chi-squared tests for categorical variables (gender, race, ethnicity, procedure, catastrophizing) were employed. Statistical significance was set at p ≤ 0.05. Data are presented as median with range values, frequencies with percentages, or adjusted odds ratios (OR) and betas (ß) with 95% confidence intervals (CI). RESULTS: There were 73 (38.6%) patients categorized as catastrophizers. Median score for social support was 90.8 (range: 3.9 to 100). No statistically significant associations between pain catastrophizing or social support were observed for length of stay (ß: 0.03, 95% CI: - 0.24-0.31, p = 0.81; ß: - 0.002, 95% CI: - 0.010-- 0.006, p = 0.58) and discharge disposition (OR: 1.15, 95% CI: 0.51-2.55, p = 0.74; OR: 0.99, 95% CI: 0.97-1.01, p = 0.37). Significant associations with discharge to a rehabilitation facility included non-Caucasian (OR: 5.4, 95% CI: 2.4-11.8, p < 0.001) and longer length of stay (OR: 1.6, 95% CI: 1.01-2.4, p = 0.04). Female gender and non-Caucasian were associated with longer length of stay (ß: 0.3, 95% CI: 0.03-0.6, p = 0.03; and ß: 0.4, 95% CI: 0.1-0.6, p=0.008, respectively). CONCLUSION: We did not find a significant association between pain catastrophizing behavior and level of social support with length of stay or discharge disposition.

Principles of Antibiotic Prophylaxis in Total Joint Arthroplasty: Current Concepts.

Infection is a rare, serious complication after total joint arthroplasty and constitutes a considerable emotional and financial burden for patients, surgeons, and healthcare systems. Prevention of surgical site and periprosthetic joint infections is crucial. This requires knowledge of the microorganisms that commonly cause these infections, including Staphylococcus species. Selection of the appropriate antibiotic regimen to treat infection remains controversial, but cefazolin and cefuroxime are the most commonly recommended antibiotics for prophylaxis. Appropriate timing of administration before surgery, with redosing performed as needed, can help to ensure optimal antibiotic concentration during surgery. Given the increasing evidence that S aureus colonization is a risk factor for periprosthetic joint infection, an exploration of the potential benefits of preoperative S aureus carrier screening and decolonization protocols is warranted. The use of antibiotic-loaded bone cement in primary total joint arthroplasty and antibiotic powder at wound closure are other controversial topics that require additional research.

Principles of Antibiotic Prophylaxis in Total Joint Arthroplasty: Current Concepts.

Infection is a rare, serious complication following total joint arthroplasty and constitutes a considerable emotional and financial burden for patients, surgeons, and healthcare systems. Prevention of surgical site and periprosthetic joint infections is crucial. This requires knowledge of the microorganisms that commonly cause these infections, including Staphylococcus species. Selection of the appropriate antibiotic regimen to treat infection remains controversial, but cefazolin and cefuroxime are the most commonly recommended antibiotics for prophylaxis. Appropriate timing of administration before surgery, with redosing performed as needed, can help to ensure optimal antibiotic concentration during surgery. Given the increasing evidence that S aureus colonization is a risk factor for periprosthetic joint infection, an exploration of the potential benefits of preoperative S aureus carrier screening and decolonization protocols is warranted. The use of antibiotic-loaded bone cement in primary total joint arthroplasty and antibiotic powder at wound closure are other controversial topics that require additional research.

Interpars - an anatomical examination of the lumbar pars interarticulares with significance for spinal decompression.

BACKGROUND: Spine procedures continue to increase significantly. As such, a more precise understanding of the anatomy, especially the pars interarticularis (PI) is critical. Current data characterizing the PI level-by-level is lacking. This study analyzed the average PI width at each level of the lumbar spine in order to elucidate statistically significant PI variations between lumbar levels. METHODS: The interpars distance, the narrowest distance between the lateral edges of the left and right PI, was measured directly with calipers on 53 complete lumbar specimens and digitally via Fastrack measurements of 30 sets of lumbar vertebrae. For both methods, the mean interpars distances were compared moving down the lumbar spine. RESULTS: For direct measurements, the average interpars distances increased from L2 to L5. Analysis revealed significant differences across all levels. A significant difference was noted between male and female vertebrae only at L1. For Fastrack measurements, the average interpars distances also increased from L2 to L5. An increase in spinal canal width was observed across all but L1-L2, and an increase in the interpars-to-spinal-canal-width ratio was noted at all levels except L1-L2 and L4-L5. CONCLUSIONS: The amount of bone in the PI available for surgical removal becomes smaller moving from L5 to L1. There is a larger "margin-for-error" at L4 and L5 when decompressing the spinal canal from one side to the other than there is in the upper lumbar spine. At L1 and L2, de- compressing the entire width of the spinal canal leaves only a millimeter of remaining pars on either side. Care should be taken to use "undercutting techniques" in upper lumbar decompressions to preserve the PI.

A systematic review of comparative studies on bone graft alternatives for common spine fusion procedures.

BACKGROUND: The increased prevalence of spinal fusion surgery has created an industry focus on bone graft alternatives. While autologous bone graft remains the gold standard, the complications and morbidity from harvesting autologous bone drives the search for reliable and safe bone graft substitutes. With the recent information about the adverse events related to bone morhogenetic protein use, it is appropriate to review the literature about the numerous products that are not solely bone morphogenetic protein. PURPOSE: The purpose of this literature review is to determine the recommendations for use of non-bone morphogenetic protein bone graft alternatives in the most common spine procedures based on a quantifiable grading system. STUDY DESIGN: Systematic literature review. METHODS: A literature search of MEDLINE (1946-2012), CINAHL (1937-2012), and the Cochrane Central Register of Controlled Trials (1940-April 2012) was performed, and this was supplemented by a hand search. The studies were then evaluated based on the Guyatt criteria for quality of the research to determine the strength of the recommendation. RESULTS: In this review, more than one hundred various studies on the ability of bone graft substitutes to create solid fusions and good patient outcomes are detailed. CONCLUSION: The recommendations for use of bone graft substitutes and bone graft extenders are based on the strength of the studies and given a grade.