Gut microbiota profiling in hematopoietic stem cell transplant recipients: Towards personalized medicine.

BACKGROUND: Antibiotic resistance in bacteria is a cause for concern, especially in hematopoietic stem cell transplant (HSCT) patients. Endogenous bowel microflora in HSCT patients get replaced by hospital multidrug resistant flora and pose risk of serious bacterial infection during the pre-engraftment stage. For decades, many methods to reduce the translocation of gut microbiota in HSCT patients have been attempted. Despite the logic, of using prophylactic antibiotics, there is no consensus on standard regimen. Personalized antibiotic prophylaxis-based on gut microbiota and clinical profile has been suggested by researchers. In this study, gut microbiota in HSCT recipients has been studied with antimicrobial susceptibility testing and detection of various antibiotic resistance phenotypes. METHODS: Seventy-six HSCT patients (2016-2018) were included. Stool surveillance cultures and antibiotic susceptibility testing were performed. Bacterial isolates were classified into various antibiotic resistance phenotypes. RESULTS: This study revealed that 73.75% HSCT recipients had gut colonized with antibiotic resistance microbiota which included extended-spectrum ß-lactamase-, multidrug- and extensively drug-resistant phenotypes. CONCLUSION: This study reiterates the importance of individual profiling of gut microbiota in HSCT patients.

Blueprinting of summative theory assessment of undergraduate medical students in microbiology.

BACKGROUND: Assessment drives learning. Written assessment of many universities lacks uniformity and validation. Subjectivity influences assessment. Blueprinting has been used as content validity tools. METHODS: In this study, last 5-year's Maharashtra University of Health Sciences (MUHS) second year MBBS papers in Microbiology were evaluated for its content validity. Desired weightage to all the topics in microbiology was given by the faculty of Department of the Microbiology. University papers were also evaluated for level of cognitive domain tested. Closed ended feedback from faculty was taken and was statistically evaluated. RESULT: Study revealed both overrepresentation and underrepresentation of many topics across all the last 5-year university papers in subject of microbiology. The cognitive dimension tested in question papers as per revised Bloom's taxonomy was merely 8% from Bloom's level 1, 20% from level 2, and 8% from level 3, whereas 64% of the questions were ambiguous. Faculty feedback revealed significant impact (P < 0.05) from blueprinting in microbiology. CONCLUSION: Assessment should be aligned to learning objectives, and blueprinting improves content validity.

Providing Coverage for the Unique Lifelong Health Care Needs of Living Kidney Donors Within the Framework of Financial Neutrality.

Organ donation should neither enrich donors nor impose financial burdens on them. We described the scope of health care required for all living kidney donors, reflecting contemporary understanding of long-term donor health outcomes; proposed an approach to identify donor health conditions that should be covered within the framework of financial neutrality; and proposed strategies to pay for this care. Despite the Affordable Care Act in the United States, donors continue to have inadequate coverage for important health conditions that are donation related or that may compromise postdonation kidney function. Amendment of Medicare regulations is needed to clarify that surveillance and treatment of conditions that may compromise postdonation kidney function following donor nephrectomy will be covered without expense to the donor. In other countries lacking health insurance for all residents, sufficient data exist to allow the creation of a compensation fund or donor insurance policies to ensure appropriate care. Providing coverage for donation-related sequelae as well as care to preserve postdonation kidney function ensures protection against the financial burdens of health care encountered by donors throughout their lives. Providing coverage for this care should thus be cost-effective, even without considering the health care cost savings that occur for living donor transplant recipients.

Towards Improving the Transfer of Care of Kidney Transplant Recipients.

Kidney transplant recipients require specialized medical care and may be at risk for adverse health outcomes when their care is transferred. This document provides opinion-based recommendations to facilitate safe and efficient transfers of care for kidney transplant recipients including minimizing the risk of rejection, avoidance of medication errors, ensuring patient access to immunosuppressant medications, avoidance of lapses in health insurance coverage, and communication of risks of donor disease transmission. The document summarizes information to be included in a medical transfer document and includes suggestions to help the patient establish an optimal therapeutic relationship with their new transplant care team. The document is intended as a starting point towards standardization of transfers of care involving kidney transplant recipients.

Reciprocity to Increase Participation of Compatible Living Donor and Recipient Pairs in Kidney Paired Donation.

Inclusion of compatible living donor and recipient pairs (CPs) in kidney paired donation (KPD) programs could increase living donor transplantation. We introduce the concept of a reciprocity-based strategy in which the recipient of a CP who participates in KPD receives priority for a repeat deceased donor transplant in the event their primary living donor KPD transplant fails, and then we review the practical and ethical considerations of this strategy. The strategy limits prioritization to CPs already committed to living donation, minimizing the risk of unduly influencing donor behavior. The provision of a tangible benefit independent of the CP's actual KPD match avoids many of the practical and ethical challenges with strategies that rely on finding the CP recipient a better-matched kidney that might provide the CP recipient a future benefit to increase KPD participation. Specifically, the strategy avoids the potential to misrepresent the degree of future benefit of a better-matched kidney to the CP recipient and minimizes delays in transplantation related to finding a better-matched kidney. Preliminary estimates suggest the strategy has significant potential to increase the number of living donor transplants. Further evaluation of the acceptance of this strategy by CPs and by waitlisted patients is warranted.

Integrating APOL1 Gene Variants Into Renal Transplantation: Considerations Arising From the American Society of Transplantation Expert Conference.

Thirteen percent of individuals of African ancestry express two variant copies of the gene encoding apolipoprotein 1 (APOL1) that has been associated with an increased risk of end-stage renal disease (ESRD) in the general population. Limited studies suggest that the survival of transplanted kidneys from donors expressing two APOL1 risk alleles is inferior to that of kidneys from donors with zero or one risk allele. In living kidney donation, two case reports describe donors expressing two APOL1 risk alleles who developed ESRD. Given the potential impact of APOL1 variants on the utility and safety of kidney transplantation and living kidney donation, the American Society of Transplantation convened a meeting with the goals of summarizing the current state of knowledge with respect to transplantation and APOL1, identifying knowledge gaps and studies to address these gaps, and considering approaches to integrating APOL1 into clinical practice. The authors recognize that current data are not sufficient to support traditional evidence-based guidelines but also recognize that it may require several years to generate the necessary data. Thus, approaches as to how APOL1 might currently be integrated into the clinical decision-making process were considered. This report summarizes the group's deliberations.

Engaging Living Kidney Donors in a New Paradigm of Postdonation Care.

Recent studies have highlighted the need for better understanding of the long-term health outcomes of living donors. Barriers to establishment of a dedicated long-term donor follow-up data system in the United States include infrastructure costs and donor retention. We propose providing all previous and future living donors with a lifelong health insurance benefit for the primary purpose of facilitating acquisition of health information after donation as an alternative to establishment of a dedicated donor follow-up data system. Donors would consent to allow collection and analysis of their medical data, and continuation of insurance coverage would require completion of regular health assessments. The extension of health insurance would be analogous to the established practice of paying people for participation in a research study and would provide a mechanism to engage donors in a new paradigm of postdonation care in which donors are actively involved in their own health maintenance. Rather than acting as an inducement for donation, providing donors with the ability to easily contribute information about their health status represents a practical strategy to acquire the long-term medical information necessary to better inform future generations of living kidney donors.

Timing of Pregnancy After Kidney Transplantation and Risk of Allograft Failure.

The optimal timing of pregnancy after kidney transplantation remains uncertain. We determined the risk of allograft failure among women who became pregnant within the first 3 posttransplant years. Among 21 814 women aged 15-45 years who received a first kidney-only transplant between 1990 and 2010 captured in the United States Renal Data System, n = 729 pregnancies were identified using Medicare claims. The probability of allograft failure from any cause including death (ACGL) at 1, 3, and 5 years after pregnancy was 9.6%, 25.9%, and 36.6%. In multivariate analyses, pregnancy in the first posttransplant year was associated with an increased risk of ACGL (hazard ratio [HR]: 1.18; 95% confidence interval [CI] 1.00, 1.40) and death censored graft loss (DCGL) (HR:1.25; 95% CI 1.04, 1.50), while pregnancy in the second posttransplant year was associated with an increased risk of DCGL (HR: 1.26; 95% CI 1.06, 1.50). Pregnancy in the third posttransplant year was not associated with an increased risk of ACGL or DCGL. These findings demonstrate a higher incidence of allograft failure after pregnancy than previously reported and that the increased risk of allograft failure extends to pregnancies in the second posttransplant year.

Advances in the understanding of complement mediated glomerular disease: implications for recurrence in the transplant setting.

Recent advances in the understanding of the role of complement in glomerular disease allow for more accurate assessment of the risk of disease recurrence after transplantation, and inform the development of targeted treatment strategies to overcome specific defects in the alternate pathway of the complement system. These advances along with remaining knowledge deficits are reviewed with specific relevance to membranoproliferative glomerulonephritis (MPGN) and C3 glomerulopathy, a heterogenous group of diseases with a high rate of recurrence leading to allograft failure. Recommendations to establish an accurate diagnosis and inform therapeutic decision making in transplant candidates with a histologic diagnosis of MPGN are provided.

Economic consequences incurred by living kidney donors: a Canadian multi-center prospective study.

Some living kidney donors incur economic consequences as a result of donation; however, these costs are poorly quantified. We developed a framework to comprehensively assess economic consequences from the donor perspective including out-of-pocket cost, lost wages and home productivity loss. We prospectively enrolled 100 living kidney donors from seven Canadian centers between 2004 and 2008 and collected and valued economic consequences ($CAD 2008) at 3 months and 1 year after donation. Almost all (96%) donors experienced economic consequences, with 94% reporting travel costs and 47% reporting lost pay. The average and median costs of lost pay were $2144 (SD 4167) and $0 (25th-75th percentile 0, 2794), respectively. For other expenses (travel, accommodation, medication and medical), mean and median costs were $1780 (SD 2504) and $821 (25th-75th percentile 242, 2271), respectively. From the donor perspective, mean cost was $3268 (SD 4704); one-third of donors incurred cost >$3000, and 15% >$8000. The majority of donors (83%) reported inability to perform usual household activities for an average duration of 33 days; 8% reported out-of-pocket costs for assistance with these activities. The economic impact of living kidney donation for some individuals is large. We advocate for programs to reimburse living donors for their legitimate costs.

Hypercalcemia in renal transplant patients: prevalence and management in Canadian transplant practice.

Hypercalcemia, occurring in up to 25% of patients within 12 months following renal transplantation, and persistent hyperparathyroidism were evaluated following renal transplantation, by retrospective chart review of 1000 adult patients transplanted between January 1, 2003 and January 31, 2008 with at least six months follow-up. Serum calcium, parathyroid hormone, and phosphate levels were recorded at 12, 24, 36, and 48 months. Average follow-up was 766 (535) d (mean (SD); median 668 d). Majority were first transplants (85%); deceased donor 57%. Point prevalence of hypercalcemia (serum Ca(2+) > 2.6 mM) was 16.6% at month 12, 13.6% at month 24, 9.5% at month 36, and 10.1% at month 48. Point prevalence of serum parathyroid hormone (PTH) > 10 pM was 47.6% at month 12, 51.1% at month 24, 43.4% at month 36, and 39.3% at month 48. Estimated glomerular filtration rate (GFR) was maintained throughout and was not different between patients with or without hypercalcemia or elevated PTH. Cinacalcet was prescribed in 12% of patients with hypercalcemia and persistent hyperparathyroidism; parathyroidectomy was performed in 112/1000 patients, 15 post-transplant. Persistent hyperparathyroidism, often accompanied by hypercalcemia, is common following successful renal transplantation, but the lack of clear management suggests the need for further study and development of evidence-based guidelines.

Quantification of the early risk of death in elderly kidney transplant recipients.

To inform decision making regarding transplantation in patients ≥ 65 years, we quantified the early posttransplant risk of death by determining the time to equal risk and equal survival between transplant recipients and wait-listed dialysis patients in the United States between 1995 and 2007 (total n = 25 468). Survival was determined using separate multivariate nonproportional hazards analyses in low-, intermediate- and high-risk cardiovascular risk patients. Compared to wait-listed patients with similar cardiovascular risk, standard criteria (SCD) and expanded criteria (ECD) recipients had a higher risk of death in the perioperative and early-posttransplant period. In contrast, low and intermediate risk living donor (LD) recipients had an immediate survival advantage compared to similar risk wait-listed patients. In all risk groups, transplantation was associated with a long-term survival advantage compared to dialysis, but there were marked differences in time to equal risk of death, and time to equal survival by donor type. For example, survival in high-risk recipients of an LD, SCD and ECD transplant became equal to that in similar risk wait-listed patients 130, 368 and 521 days after transplantation. Early posttransplant mortality risk is eliminated in low- and intermediate-risk patients, and markedly reduced in high-risk patients with LD transplantation.

The survival benefit of kidney transplantation in obese patients.

Obese patients have a decreased risk of death on dialysis but an increased risk of death after transplantation, and may derive a lower survival benefit from transplantation. Using data from the United States between 1995 and 2007 and multivariate non-proportional hazards analyses we determined the relative risk of death in transplant recipients grouped by body mass index (BMI) compared to wait-listed candidates with the same BMI (n = 208 498). One year after transplantation the survival benefit of transplantation varied by BMI: Standard criteria donor transplantation was associated with a 48% reduction in the risk of death in patients with BMI ≥ 40 kg/m(2) but a ≥ 66% reduction in patients with BMI < 40 kg/m2. Living donor transplantation was associated with ≥ 66% reduction in the risk of death in all BMI groups. In sub-group analyses, transplantation from any donor source was associated with a survival benefit in obese patients ≥ 50 years, and diabetic patients, but a survival benefit was not demonstrated in Black patients with BMI ≥ 40 kg/m(2). Although most obese patients selected for transplantation derive a survival benefit, the benefit is lower when BMI is ≥ 40 kg/m(2), and uncertain in Black patients with BMI ≥ 40 kg/m(2).

Lower incidence of inappropriate shock therapy in patients with combined cardiac resynchronisation therapy defibrillators (CRT-D) compared with patients with non-CRT defibrillators (ICDs).

INTRODUCTION: A significant number of patients experience inappropriate shock therapy (IST) from implantable cardioverter-defibrillators (ICD). An increasing number of patients with advanced heart failure receive combined ICD and cardiac resynchronisation therapy devices (CRT-D). The incidence of IST in this group is less well described. We aimed to assess the incidence and predictors of IST in CRT-D patients. METHODS: A retrospective cohort study of prospectively collected data on patients who received an ICD and CRT-D between October 2007 and January 2009 at our institution were studied. The primary outcome measures were the IST event rate and all-cause mortality. RESULTS: A total of 185 patients with ICD/CRT-D (100/85) were included in the analysis. Eighteen patients experienced 35 episodes of IST during the follow-up (21 ± 13 months). There was a significantly lower IST cumulative event rate in the CRT-D vs. ICD group, 5% (CI: 1-13%) vs. 19% (95% CI: 11-30%) by 24 months, (p = 0.017). The majority of the IST was caused by atrial arrhythmias with atrial fibrillation accounting for 28 episodes of IST in nine patients. Multivariate analysis using Cox hazard model including baseline characteristics and coexisting appropriate shock therapy showed that a history of atrial fibrillation/flutter was the strongest independent predictor of IST with a hazard ratio of 3.53 (p = 0.019). CONCLUSION: Patients with CRT-D had a significantly lower incidence of IST compared with patients receiving an ICD. Given that atrial arrhythmia remained the commonest trigger for IST, our finding lends support to the hypothesis that CRT may reduce atrial fibrillation burden in patients receiving CRT-D.

Yield and fibre quality associated with cotton leaf curl disease of Bt-cotton in Punjab.

Cotton leaf curl disease (CLCuD), caused by Gemini virus and transmitted through whitefly (Bemisia tabaci) is a serious problem in Northern India, affecting the productivity to a great extent. Depending upon the severity of infection in susceptible varieties, the disease can cause upto 90.0 % yield losses besides this, it also causes deterioration in fibre quality. The objective of the present study was to determine the effect of cotton leaf curl disease on seed cotton yield and fibre characters of two popular Bt-cotton hybrids in Punjab. The disease caused 52.7% reduction in number of bolls and 54.2 % in boll weight in Bt cotton hybrid RCH 134. Similarly, it reduced the fibre length from 29.1 to 26.2 mm (9.9%); fibre uniformity from 68.9 to 68.1% (1.1%); fibre strength from 29.1 to 26.9 g per texture (7.5%) and miconaire value from 5.2 to 5.0 g inch(-1) (3.8%). Similar results were reported in Bt cotton hybrid MRC 6304, where the disease reduced the boll number and boll weight by 46.1 and 43.4%, respectively. However, to the fibre quality was not much affected by varying level of disease severity. The studies clearly reflect the adverse impact of CLCuD on yield and fibre quality especially 2.5% span length. Thus suggesting the management of disease using integrated disease management strategies to avoid quantitative and qualitative losses.

Income of living kidney donors and the income difference between living kidney donors and their recipients in the United States.

Disincentives for living kidney donation are common but are poorly understood. We studied 54 483 living donor kidney transplants in the United States between 2000 and 2009, limiting to those with valid zip code data to allow determination of median household income by linkage to the 2000 U.S. Census. We then determined the income and income difference of donors and recipients. The median household income in donors and recipients was $46 334 ±$17 350 and $46 439 ±$17 743, respectively. Donation-related expenses consume ≥ 1 month's income in 76% of donors. The mean ± standard deviation income difference between recipients and donors in transplants involving a wealthier recipient was $22 760 ± 14 792 and in 90% of transplants the difference was <$40 000 dollars. The findings suggest that the capacity for donors to absorb the financial consequences of donation, or of recipients to reimburse allowable expenses, is limited. There were few transplants with a large difference in recipient and donor income, suggesting that the scope and value of any payment between donors and recipients is likely to be small. We conclude that most donors and recipients have similar modest incomes, suggesting that the costs of donation are a significant burden in the majority of living donor transplants.

The impact of pancreas transplantation on kidney allograft survival.

Whether pancreas after kidney transplantation (PAK) compromises kidney allograft survival, and what pre-PAK glomerular filtration rate (GFR) should be used to select patients for PAK is unclear. We analyzed all (n = 2776) PAK recipients in the United States between 1989 and 2007 and compared their risk of kidney failure to a comparator group of n = 13 635 young adult diabetic kidney only transplant recipients during the same time after accounting for selection bias by the use of a propensity score for PAK in a multivariate time to event analysis. In a secondary analysis, we determined the association of pre-PAK GFR with subsequent kidney allograft survival. Despite an increased risk of death early after pancreas transplantation, PAK recipients had a decreased long-term risk of kidney allograft failure compared to diabetic kidney only transplant recipients HR = 0.89; 95% CI: [0.78-1.00]; p = 0.05. An association of pre-PAK GFR with kidney survival was not evident until 3 years after pancreas transplantation, and patients with a pre-PAK GFR of 30-39 mL/min still attained 10-year post-PAK kidney survival of 69%. We conclude that PAK is associated with improved kidney allograft survival, and pre-PAK GFR 30-39 mL/min should not preclude PAK. Expanded use of PAK is warranted.