Risk stratification of renal transplant recipients using routine parameters: Implication of learning from SARS-CoV-2 into transplant follow-up program.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation. In the course of acute SARS-CoV-2 infection, various laboratory markers have been identified as predictors for high risk of mortality. AIM: To risk stratify renal transplant recipients (RTxR) using general demographic parameters, comorbidities and routine laboratory markers for the severity of the disease and its outcomes. We believe that learning about these routinely moni tored parameters can help us plan better strategies for the RTxR follow-up program. METHODS: This present study includes RTxR who acquired SARS-CoV-2 infection from March 2020 to February 2021. We recorded the basic demographics, comorbidities and routine laboratory markers. We investigated the impact of SARS-CoV-2 infection on RTxRs and risk-stratified the progression of disease severity and outcomes in terms of recovery or mortality. RESULTS: From 505 RTxRs in our renal transplant follow-up program, 29 (7.75%) RTxRs had PCR-positive SARS-CoV-2 infection. We recorded 8 deaths from SARS-CoV-2 infection giving an overall mortality rate of 1.6% but a significant 27.6% mortality in SARS-CoV-2 positive recipients. Age more than 68 years, non-Caucasian ethnicity and male gender were associated with a significant drop in survival probability; P ≤ 0.001. < 0.001 and < 0.0001 respectively. 87.5% of the deceased were diabetic; P ≤ 0.0.0001. Estimated glomerular filtration rate of less than 26 mL/min/1.73 m2, serum albumin less than 20 g/L, Hemoglobin less than 9.6 g/L and serum calcium less than 1.70 mmol/L were all associated with significantly increased risk of mortality; P = 0.0128, < 0.001, < 0.0001 and 0.0061 respectively. CONCLUSION: This study has identified some routinely used modifiable parameters in predicting a higher risk of mortality and morbidity. This knowledge can be used in RTxR follow-up programs by addressing these parameters early to help reduce the morbidity and mortality in RTxRs.

Long non-coding RNAs regulated NF-κB signaling in cancer metastasis: Micromanaging by not so small non-coding RNAs.

Cancer metastasis is a major reason for the cancer-associated deaths and a role of long non-coding RNAs (lncRNAs) in cancer metastasis is increasingly being realized. Among the many oncogenic pathways, NF-κB signalling's involvement in cancer metastasis as a key inflammation-regulatory transcription factor has been a subject of interest for long time. Accumulating data from in vitro as well as in vivo studies along with analysis of clinical cancer tissues points to regulation of NF-κB signalling by lncRNAs with implications toward the onset of cancer metastasis. LncRNAs FOXD2-AS1, KRT19P3 and the NF-κB interacting lncRNA (NKILA) associate with lymph node metastasis and poor prognosis of individual cancers. The role of epithelial-mesenchymal transition (EMT) in cancer metastasis is well known. EMT is regulated by NF-κB and regulation of NF-κB/EMT-induced metastasis by lncRNAs remains a hot topic of research with indications for such roles of lncRNAs MALAT1, SNHG15, CRNDE and AC007271.3. Among the many lncRNAs, NKILA stands out as the most investigated lncRNA for its regulation of NF-κB. This tumor suppressive lncRNA has been reported downregulated in clinical samples representing different human cancers. Mechanistically, NKILA has been consistently shown to inhibit NF-κB activation via inhibition of IκBα phosphorylation and the resulting suppression of EMT. NKILA is also a target of natural anticancer compounds. Given the importance of NF-κB as a master regulatory transcription factor, lncRNAs, as the modulators of NF-κB signaling, can provide alternate targets for metastatic cancers with constitutively active NF-κB.

The impact of coronavirus disease 2019 pandemic on working dynamics of junior and middle grade doctors in the United Kingdom: Learning from their experience requires immediate improvement in health care planning and management-An outcome analysis of a nationwide survey.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019) pandemic had an unprecedented impact on health services across the world resulting in increased demand of intensive care capacity, opening Nightingale hospitals, and mass movement of doctors across various specialities. This unplanned redeployment raised concerns among various health care workers. The objective of the current study is to explore working dynamics and experience of junior and middle grade doctors during current pandemic. METHODS: We organised a nationwide cross-sectional survey of junior and middle grade doctors working in the United Kingdom. The survey was aimed to study their level of participation during coronavirus disease 2019 pandemic and its impact on their clinical practices and well-being. RESULTS: In total, 1564 completed questionnaires with representations from all regions of the United Kingdom were included. The mean age of respondents was 30.64 years (95% confidence interval +1.025; standard deviation = 9.9057). There were 51.5% females with significantly more participants from Black, Asian, and minority ethnic group (n = 835, p = 0.0073); 963 (61.6%, p ⩽ 0.0001) doctors were redeployed outside their primary speciality. The major redeployments were from other specialities to Intensive Therapy Units (41.8%, p ⩽ 0.001); 63.3% of respondents spend more than 8 weeks in redeployed speciality (p ⩽ 0.0001). There was a significant impact of coronavirus disease 2019 on personal, mental, and physical well-being of doctors. The major areas requiring immediate attention include proper leadership and clinical support (64.1%), pre-redeployment planning and induction (48.5%), redeployment according to the skills and/or in familiar specialities (44.6%), and regular mental and physical well-being checks (37%). CONCLUSION: The outcome of the survey concluded with four major recommendations, including the need to have a named supervisor for these doctors, structured induction program, regular well-being checks, and involving them in crisis planning. These recommendations will help to shape future health care policies and management particularly when it is related to redeployment of doctors during any crisis or pandemic.

Safety and Efficacy of Kidney Transplants From Older Adult Living Donors: A Comparative Analysis of Donor and Recipient Outcomes.

OBJECTIVES: We investigated the safety of donor nephrectomy from older adult donors (age ≥60 years), as well as long-term donor, recipient, and graft outcomes. MATERIALS AND METHODS: We retrospectively analyzed data from 307 living donor kidney transplants from 1996 to 2016 and defined 2 cohorts based on donor age. Cohort A comprised donors aged 60 years and older, and cohort B comprised donors from 18 to 59 years old. We recorded donor and recipient perioperative complications, outcomes, and survival rates and used SPSS and MedCalc statistical software programs for data analyses. RESULTS: The mean follow-up period for donor-recipient pairs in cohort A was 97 months (SD, 25.1 months) with median 108 months (IQR, 92-108 months) and in cohort B was 100.57 months (SD, 25.45 months) with median 120 months (IQR, 84-120 months). Mean donor age in cohort A was 64.13 years (SD, 3.78 years) with median 63 years (IQR, 61-66.5 years) and in cohort B was 41.08 years (SD, 9.15 years) with median 41 years (IQR, 34.5-48 years) (P < .001, cohort A vs B). Mean recipient age in cohort A was 47.65 years (SD, 14.26 years) with median 48.5 years (IQR, 35.5-61 years) and in cohort B was 43.55 years (SD, 13.15 years) with median 40.5 years (IQR, 33.5-54 years) (P < .001, cohort A vs B). Both cohorts showed no significant differences in perioperative donor and recipient complications. Renal function (measured as estimated glomerular filtration rate) in remaining native kidneys of cohort A showed no significant decline during median 8-year follow-up (P = .089 and P < .414, respectively). There were no significant differences in survival rates for donors, recipients, and grafts. CONCLUSIONS: Living donor kidney transplant from older adult donors is safe and effective with good long-term patient and allograft survival.

Cardiovascular Risk Assessment in Elderly Living Kidney Donors: Risk Comparison Before and After Donation Using QRISK Equation.

OBJECTIVES: This study aimed to assess whether donor age would increase the risk of cardiovascular comorbidities during the first few years after donation. Cardiovascular risk was calculated using the QRISK tool (University of Nottingham and EMIS, Nottingham, UK). MATERIALS AND METHODS: Data were collected from 221 living renal transplant donors at St. George's University Hospital NHS Foundation Trust between 2008 and 2012 before and after donation (at 6, 12, and 24 mo). QRISK scores were calculated for each patient at these time points before stratifying our patients into 2 cohorts: cohort A (age ≤ 59 y) and cohort B (age ≥ 60 y). QRISK scores were then compared using unpaired t tests. RESULTS: Before donation, mean QRISK scores were 3.4% in cohort A and 12.4% in cohort B (P < .001). At 6, 12, and 24 months after kidney donation, the risks were 3.3% and 12.2% (P < .001), 3.8% and 13.6% (P < .001), and 5% and 15.4% (P < .001) in cohort A versus cohort B. CONCLUSIONS: When we analyzed risk before donation, both age groups showed a significant increase in cardiovascular risk at 24 months. This subtle increase in cardiovascular risk in the 2 groups may be attributed to changing patient demographics, such as the increasing age of patients, rather than the donation itself. Elderly kidney donors, therefore, are a key source of donation after satisfactory cardiovascular work-up. However, elderly kidney donors will require long-term postoperative follow-up care and specific counseling aimed at reducing modifiable cardiovascular risk factors.