Impact of functional status on outcomes of simultaneous pancreas-kidney transplantation: Risks and opportunities for patient benefit

Background. The impact of functional status on survival among simultaneous pancreas-kidney transplant (SPKT) candidates and recipients is not well described. Methods. We examined national Scientific Registry of Transplant Recipients (SRTR) data for patients listed for SPKT in the United States (2006-2019). Functional status was categorized by center-reported Karnofsky Performance Score (KPS). We used Cox regression to quantify associations of KPS at listing and transplant with subsequent patient survival, adjusted for baseline patient and transplant factors (adjusted hazard ratio,(95% LCL)aHR(95%UCL)). We also explored time-dependent associations of SPKT with survival risk after listing compared with continued waiting in each functional status group. Results. KPS distributions among candidates (N = 16 822) and recipients (N = 10 316), respectively, were normal (KPS 80-100), 62.0% and 57.8%; capable of self-care (KPS 70), 23.5% and 24.7%; requires assistance (KPS 50-60), 12.4% and 14.2%; and disabled (KPS 10-40), 2.1% and 3.3%. There was a graded increase in mortality after listing and after transplant with lower functional levels. Compared with normal functioning, mortality after SPKT rose progressively for patients capable of self-care (aHR,(1.00)1.18(1.41)), requiring assistance (aHR,(1.06)1.31(1.60)), and disabled (aHR,(1.10)1.55(2.19)). In time-dependent regression, compared with waiting, SPKT was associated with 2-fold mortality risk within 30 days of transplant. However, beyond 30 days, SPKT was associated with reduced mortality, from 52% for disabled patients (aHR,(0.26)0.48(0.88)) to 70% for patients with normal functioning (aHR,(0.26)0.30(0.34)). Conclusions. While lower functional status is associated with increased mortality risk among SPKT candidates and recipients, SPKT can provide long-term survival benefit across functional status levels in those selected for transplant

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Outcomes of kidney transplantation in patients with hepatitis B virus infection: A systematic review and meta-analysis

AIM To assess outcomes of kidney transplantation including patient and allograft outcomes in recipients with hepatitis B virus (HBV) infection, and the trends of patient's outcomes overtime. METHODS A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through October 2017. Studies that reported odds ratios (OR) of mortality or renal allograft failure after kidney transplantation in patients with HBV [defined as hepatitis B surface antigen (HBsAg) positive] were included. The comparison group consisted of HBsAg-negative kidney transplant recipients. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017080657). RESULTS Ten observational studies with a total of 87623 kidney transplant patients were enrolled. Compared to HBsAg-negative recipients, HBsAg-positive status was significantly associated with increased risk of mortality after kidney transplantation (pooled OR = 2.48; 95% CI: 1.61-3.83). Meta-regression showed significant negative correlations between mortality risk after kidney transplantation in HBsAg-positive recipients and year of study (slopes = -0.062, P = 0.001). HBsAg-positive status was also associated with increased risk of renal allograft failure with pooled OR of 1.46 (95% CI: 1.08-1.96). There was also a significant negative correlation between year of study and risk of allograft failure (slopes = -0.018, P = 0.002). These associations existed in overall analysis as well as in limited cohort of hepatitis C virus-negative patients. We found no publication bias as assessed by the funnel plots and Egger's regression asymmetry test with P = 0.18 and 0.13 for the risks of mortality and allograft failure after kidney transplantation in HBsAg-positive recipients, respectively. CONCLUSION Among kidney transplant patients, there are significant associations between HBsAg-positive status and poor outcomes including mortality and allograft failure. However, there are potential improvements in patient and graft survivals in HBsAg-positive recipients overtime

Risk Factors and Management of Osteoporosis Post-Transplant

Bone and mineral disorders are common after organ transplantation. Osteoporosis post transplantation is associated with increased morbidity and mortality. Pathogenesis of bone disorders in this particular sub set of the population is complicated by multiple co-existing factors like preexisting bone disease, Vitamin D deficiency and parathyroid dysfunction. Risk factors include post-transplant immobilization, steroid usage, diabetes mellitus, low body mass index, older age, female sex, smoking, alcohol consumption and a sedentary lifestyle. Immunosuppressive medications post-transplant have a negative impact on outcomes, and further aggravate osteoporotic risk. Management is complex and challenging due to the sub-optimal sensitivity and specificity of non-invasive diagnostic tests, and the underutilization of bone biopsy. In this review, we summarize the prevalence, pathophysiology, diagnostic tests and management of osteoporosis in solid organ and hematopoietic stem cell transplant recipients

The Use of Donor-Derived Cell-Free DNA for Assessment of Allograft Rejection and Injury Status

Patient monitoring after kidney transplantation (KT) for early detection of allograft rejection remains key in preventing allograft loss. Serum creatinine has poor predictive value to detect ongoing active rejection as its increase is not sensitive, nor specific for acute renal allograft rejection. Diagnosis of acute rejection requires allograft biopsy and histological assessment, which can be logistically challenging in some cases and carries inherent risk for complications related to procedure. Donor-derived cell-free DNA (dd-cfDNA), DNA of donor origin in the blood of KT recipient arising from cells undergoing injury and death, has been examined as a potential surrogate marker for allograft rejection. A rise in dd-cfDNA levels precedes changes in serum creatinine allows early detections and use as a screening tool for allograft rejection. In addition, when used in conjunction with donor-specific antibodies (DSA), it increases the pre-biopsy probability of antibody-mediated rejection (ABMR) aiding the decision-making process. Advancements in noninvasive biomarker assays such as dd-cfDNA may offer the opportunity to improve and expand the spectrum of available diagnostic tools to monitor and detect risk for rejection and positively impact outcomes for KT recipients. In this this article, we discussed the evolution of dd-cfDNA assays and recent evidence of assessment of allograft rejection and injury status of KT by the use of dd-cfDNA

Risk Factors and Management of Osteoporosis Post-Transplant

Bone and mineral disorders are common after organ transplantation. Osteoporosis post transplantation is associated with increased morbidity and mortality. Pathogenesis of bone disorders in this particular sub set of the population is complicated by multiple co-existing factors like preexisting bone disease, Vitamin D deficiency and parathyroid dysfunction. Risk factors include post-transplant immobilization, steroid usage, diabetes mellitus, low body mass index, older age, female sex, smoking, alcohol consumption and a sedentary lifestyle. Immunosuppressive medications post-transplant have a negative impact on outcomes, and further aggravate osteoporotic risk. Management is complex and challenging due to the sub-optimal sensitivity and specificity of non-invasive diagnostic tests, and the underutilization of bone biopsy. In this review, we summarize the prevalence, pathophysiology, diagnostic tests and management of osteoporosis in solid organ and hematopoietic stem cell transplant recipients

Approach to pancreas transplant during the COVID‐19 pandemic

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/166434/1/ctr14177.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/166434/2/ctr14177_am.pd