POST KIDNEY TRANSPLANT NEUTROPAENIA IN SOUTHERN TASMANIA

S KUO1, M JOSE1,2, L JEFFS1, G KIRKLAND1, S YEW1, R YU1
1Royal Hobart Hospital, Hobart, Australia, 2School of Medicine, University of Tasmania, Hobart, Australia

Aim: To determine the incidence of post kidney transplant neutropaenia in Southern Tasmania, its effect on outcome and identify factors associated with increased risk of neutropaenia.
Background: Post-transplant neutropaenia is common and has been associated with poor outcomes. Nonetheless, the optimal management strategy and factors associated with neutropaenia remain unclear.
Methods: A retrospective study was performed on patients (>18 years) who received kidney or kidney-pancreas transplant between 2007-2017. Incidence of and clinical parameters surrounding neutropaenia (<1500 cells/microL) were determined. Pre-transplant parameters and outcome at one year post-transplant were compared to those who did not become neutropaenic.
Results: Of the 105 people who received a transplant (54% male, mean age 49), 54 (51%) first became neutropaenic at a mean time of 115 days post-transplantation with 26% experiencing more episodes subsequently. Post-transplant neutropaenia is associated with increased incidence of infection (68% vs 37%, p<0.05) and infection-related hospital admissions (49% vs 6%, p<0.05). There was a non-statistically significant association with more frequent rejection. CMV positive to negative transplant was associated with increased risk of post-transplant neutropaenia (38% vs 14%, p<0.05). Immunosuppression dose, Trimethoprim/Sulfamethoxazole use and Valgancyclovir use the time of neutropaenia was similar in both groups. There was no statistical significant association found in age at transplantation, gender, previous immunosuppression, type of donor, presence of donor specific antibody, human leukocyte antigen mismatch, ABO compatibility or delayed graft function. Clinician response varied often involving adjustment of multiple medications.
Conclusions: Post-transplant neutropaenia is common and is associated with increased rate of infection with the main risk factor identified being CMV positive to negative transplant.


Biography:
Renal registrar at Royal Hobart Hospital

THE ASSOCIATION OF BODY MASS INDEX CHANGE ONE YEAR POST KIDNEY TRANSPLANTATION WITH GRAFT AND PATIENT SURVIVAL: A COMPARATIVE STUDY BETWEEN INDIGENOUS AND NON-INDIGENOUS AUSTRALIANS

P SUBRAMANI1, S ULLAH2,3,4, W MAJONI5,6,7, J HUGHES2,5,6,7, S MCDONALD1,2,3
1Central Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, Australia, 2Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, Adelaide, Australia, 3University of Adelaide School of Medicine, Faculty of Health and Medical Sciences, Adelaide, Australia, 4South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia, 5Department of Nephrology, Royal Darwin Hospital, Darwin, Australia, 6Menzies School of Health Research, Wellbeing and Preventable Chronic Diseases, Darwin, NT, Darwin, Australia, 7Flinders University Faculty of Medicine, Nursing and Health Sciences, Northern Territory Medical Program, Darwin, Australia

Aim: To compare the association of body mass index (BMI) change in the first year post kidney transplantation with graft and patient survival in Indigenous and non-Indigenous Australians.
Background: Significant post-transplant weight loss or gain is associated with poorer transplant outcomes in non-Indigenous Australians. There is little data comparing early weight change with outcomes between Indigenous and non-Indigenous recipients.
Method: ANZDATA Registry data was used to examine these issues. All adult patients (aged 18+) who received a deceased donor primary kidney-only transplant from 1997-2016 were included. Percentage BMI change at 1-year post transplant was calculated. Outcomes were death censored graft loss and death with functioning graft. The associations were analysed using multivariate Cox proportional hazard models with confounder adjustments.
Results: A total of n=6776 non-Indigenous and n=387 Indigenous recipients were included in this study. Over half the recipients in both groups gained BMI in the first year; 23.1% non-Indigenous and 22.3% Indigenous lost BMI. The risk of graft loss and death were increased in the >10% and 5-10% BMI loss categories (adjusted HR 1.9 (1.6-2.4) and 1.5 (1.2-1.8)  respectively (p <0.001) for graft loss and 1.8 (1.4-2.3) and 1.4 (1.1-1.8) respectively (p <0.01) for death) in the non-Indigenous group. These risks were greater (HR 3.0 (1.4-6.5) and 2.6 (1.3-5.3) (p<0.01) for graft loss and 2.1 (0.9-5.1) (p = 0.10) and 3.0 (1.4-6.6) (p<0.01)) in the Indigenous group. There was no increase risk in graft loss or death associated with BMI gain.Conclusion: BMI loss following kidney transplantation is associated with poor survival outcomes with a greater effect amongst Indigenous recipients. BMI loss can therefore be used as a risk marker of outcome in clinical practice.
Conclusion: BMI loss following kidney transplantation is associated with poor survival outcomes with a greater effect amongst Indigenous recipients. BMI loss can therefore be used as a risk marker of outcome in clinical practice


Biography: Priyanka Subramani is currently a final year nephrology trainee at Royal Adelaide Hospital, having spent two years in the Northern Territory, prior to that. Having completed her undergradate medical degree at The University of Adelaide in 2010, she went on to pursue a career as a physician at Monash Health. She has a keen interest in Indigenous health and developing world medicine and is looking to further her experience abroad next year.

KIDNEY TRANSPLANT AND RECIPIENT OUTCOMES IN HYPEROXALURIA.

V HERON1,2, P KERR2, J KANELLIS2, K POLKINGHORNE2, N ISBEL3, E SEE2
1Renal Service, Darling Downs Hospital And Health Service, Toowoomba, Australia, 2Department of Nephrology, Monash Health, Clayton, Australia, 3Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia

Aim: To evaluate graft and patient outcomes following kidney transplantation in end stage kidney disease (ESKD) secondary to hyperoxaluria using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry.
Background: Hyperoxaluria has presented a challenge for transplant physicians given the risk of disease recurrence in the graft. There has been no analysis of transplant and patient outcomes using the ANZDATA registry.
Methods: This cohort study compared the outcomes of all patients with ESKD secondary to hyperoxaluria who received a kidney transplant in Australia and New Zealand between 1965 and 2015 to propensity score matched controls with ESKD secondary to reflux nephropathy. The primary outcome measure was graft survival. Secondary outcomes included estimated glomerular filtration rate (eGFR), acute rejection and patient survival.
Results: Nineteen kidney transplants were performed in 16 patients with hyperoxaluria between September 1965 and December 2015. Median graft survival was 1.8 years (IQR 0.4–10.6) in hyperoxaluria recipients compared to 6.8 years (IQR 2.7–13.0) in reflux nephropathy controls. Compared to reflux nephropathy, hyperoxaluria was not associated with an increased risk of graft failure (SHR 2.43, 95% CI 0.94—6.22, p=0.07). The most common cause of graft failure in the hyperoxaluria cohort was recurrent disease in contrast to chronic allograft nephropathy for reflux nephropathy recipients. Hyperoxaluria was associated with a higher post-transplant serum creatinine, but not with an increased risk of acute rejection or death.
Conclusion: Compared to reflux nephropathy, ESKD secondary to hyperoxaluria was not associated with inferior graft survival, patient survival, or acute rejection risk. However, post-transplant serum creatinine was higher and there was a shorter time to graft failure.


Biography:
Vanessa Heron is an advanced trainee in nephrology currently working at Toowoomba Hospital, Queensland.

BALLOON ANGIOPLASTY WITH CLOT LYSIS AS A FIRST LINE MEASURE FOR SALVAGE OF THROMBOSED ARTERIO-VENOUS ACCESS (AVA)

C WILKINSON1, M MANTHA1, S DHEDA1
1Cairns Base Hospital (Queensland Health), Cairns, Australia

Aim: To assess long-term outcome of thrombolysis plus balloon angioplasty of thrombosed fistulae.
Background: A thrombosed AVA often necessitates an emergent central catheter to facilitate immediate haemodialysis and then surgical intervention. Most thrombosis is due to significant stenosis limiting flow.  Early intervention may salvage the AVA.  We reviewed the immediate success and long-term outcomes of these interventions.
Methods: We present a retrospective observational study of the rates of percutaneous angioplasty of thrombosed AVAs from our health service since 2010.   Initial success was defined as on table return of flow. Ongoing patency was defined as effective dialysis at 3, 6 and 12 months in the absence of further intervention.   Data collected from the medical records included date of fistula creation, percutaneous and surgical interventions prior and following the thrombolysis events.
Results: 30 patients received 43 thrombolysis/angioplasty episodes.  The mean time to first thrombosis was 4.8 years with a prior mean 4.6 angioplasty procedures/ patient. All AVA were in the upper limbs; 80% were fistulae and 20% were grafts.  Cause of thrombosis was stenosis in 93% of the episodes.  Mean time to lysis was 1.6 days with 95% performed in outpatient setting.  The initial success rate was 97%.  15 episodes (35%) required central line access within the first week following procedure. AVA patency was 44% at 3 months, 36% at 6 months and 20% at 12 months.  By 12 months, 25% of AVAs had subsequent angioplasty and were functional, 10 patients required formation of new AVA; and 3 patients were dialysing via a permacath.
Conclusion: Following AVA thrombosis, percutaneous intervention avoided emergent central catheter insertion in 65% of patients, surgical intervention was avoided in 57% of patients.


Biography:
Dr Catherine Wilkinson is a advanced trainee in nephrology, currently based at Cairns Hospital.

EFFECTIVENESS OF MULTIMODAL INTERVENTIONS IN IMPROVING ARTERIOVENOUS FISTULA (AVF) USE OF NEW PLANNED HAEMODIALYSIS PATIENTS – A SINGLE CENTRE STUDY

PG TAN1, D LANGSFORD1, T PIANTA1, D BARIT1
1Northern Health, Epping, Australia

Aim: To evaluate if multidisciplinary interventions increase AVF use at time of planned haemodialysis initiation.
Background: The Victorian Key Performance Indicator (KPI) for commencement of planned haemodialysis with an AVF is 70%. In 2015, a multidisciplinary approach to improve fistula use at haemodialysis initiation was commenced: one-on-one chronic kidney disease education, use of vascular led arteriovenous ultrasound mapping and a combined nephrologist-vascular surgical AVF planning and triage clinic.
Methods: Patients commencing planned haemodialysis, AVF creation and prevalent use of permacath between 1/1/15 and 31/12/17 were retrospectively analysed. Quarterly KPI data from June 2015 to December 2017 was compared to state average. Patients that underwent pre-dialysis AVF creation were retrospectively stratified into low- or high-risk of dialysis need based on calculated 8-Variable Kidney Failure Risk Equation (KFRE) from demographic and renal specific data at time of vascular referral.
Results: Across the study period, 68 patients commenced haemodialysis whilst 85 underwent AVF creation. AVF use upon haemodialysis commencement consistently improved from 57% to 91%, compared to the statewide average of 56%-66%. Prevalent permacath rate fell from 18.3% to 10%.  Pre-dialysis AVF creation had increased from 74% to 85%. Amongst those who started dialysis with catheters, 50% had poor engagement with the Unit and 22% had late decision change regarding preferred dialysis modality. High-risk patients with KFRE score ≥20% had shorter waiting time for AVF creation (median 45 days(IQR95.75-294.25) vs 142days(IQR30-115), p-value <0.001) but no difference in time from access creation to dialysis commencement. There were no significant changes in patient characteristics over this period.
Conclusions: Multimodal interventions including joint assessment by nephrologists and vascular surgeons may improve triaging of patients and AVF use at haemodialysis commencement.


Biography:
Pek Ghe Tan is one of the Renal advanced trainee in Victoria. She is currently in her final year of training at the Northern Hospital.

A PILOT STUDY OF WEARABLE DEVICES TO DETECT SEPSIS

J YO1, C KARSCHIMKUS2, S CHRISTOV3, F VOLPATO4, P CHAMPION DE CRESPIGNY5, SG HOLT6
1Melbourne Health, Parkville, Australia, 2Melbourne Health, Parkville, Australia, 3Melbourne Health, Parkville, Australia, 4Freelance Signal Analyst, Melbourne, Australia, 5Melbourne Health, Parkville, Australia, 6Melbourne Health, Parkville, Australia

Aim: Health monitoring devices are popular, accepted and purchased by many patients. We assessed the feasibility of a watch device to detect infection.
Background: Infection is an important cause of morbidity and mortality among patients with kidney disease, and early identification and treatment reduces mortality. Diagnosis remains a challenge, but fever is a relatively reliable sign.
Methods: We conducted a single-center prospective cross-sectional pilot study of in-patients to demonstrate proof of concept. Patients randomly admitted under the nephrology unit between August 2017 and April 2018 were consented to wear a monitoring device. Participants wore a clinical grade device that measured peripheral temperature at the wrist (Empatica E4) along with other physiological variables, and we report early analysis of temperature (t) alone. We classified patients as having sepsis, no sepsis and/or treated sepsis and examined how well t correlated with the presence of sepsis.
Results: 104 patients underwent data recording and 82 patients had complete data. 58 patients had no sepsis,15 patients had sepsis and 9 patients had treated sepsis. None of the 41 patients who had at least 84% of readings <35°C had active sepsis. Of the 41 patients with greater than 16% of readings ≥35°C, 15 had sepsis (PPV=21%, NPV=100%). 9/10 patients who had >0.5% of readings ≥37°C had sepsis (PPV=52%, NPV=92%) (1 false positive was admitted with limb ischaemia after occlusion of a vascular graft).
Conclusion: Peripheral temperature measurement may add value to sepsis detection. Further data analysis is underway to refine the detection algorithm. We hope to be able to incorporate such algorithms into a consumer device that can continuously monitor and signal the user of impending infection.


Biography:
Dr. Jennifer Yo is currently a final year Advanced Nephrology Trainee at Melbourne Health.

CKD.QLD: ASSOCIALTION OF MONOCLONAL GAMMOPATHIES AND CHRONIC KIDNEY DISEASE

S WILKINSON1, S VENUTHURUPALLI1,2,3, A CAMERON2,3,4, HG HEALY2,3,4, R FASSETT2,5,6, WE HOY2,3
1Darling Downs Hospital And Health Service, Toowoomba, Australia, 2NHMRC CKD.CRE and CKD.QLD, The University of Queensland, Brisbane, Australia, 3School of Clinical Medicine, Faculty of Medicine, The University of Queensland, Brisbane, Australia, 4Kidney Health Service (RBWH), Metro North Hospital and Health Service, Brisbane, Australia, 5School of Human Movement Studies, The University of Queensland, Brisbane, Australia, 6Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia

Aim: To explore the association between monoclonal gammopathies and chronic kidney disease (CKD)
Background: Chronic kidney disease (CKD) is a common complication of monoclonal gammopathies with multiple myeloma being the most widely recognized. In 2012, the International Kidney and Monoclonal Gammopathy (MG) Research Group introduced a new term, monoclonal gammopathy of renal significance (MGRS), which describes a group of renal disorders caused by a monoclonal immunoglobulin, or its components.
Methods: Records of CKD registry of patients attending renal clinics from the Darling Downs with documented monoclonal gammopathies were reviewed for demographic profile, renal biopsy rates, diagnostic ascertainment of CKD.
Results: A total of 27 (1.9%) cases were identified from 1400 recruited to the CKD Registry, with a median age of 68.9 years with male preponderance (59.2%).  A quarter of them (7/27) had confirmed multiple myeloma. Of the remaining 20 cases MGRS was diagnosed by renal histology in four (20%) with one each of AL amyloidosis, fibrillary nephropathy, monoclonal immune deposition disease (MIDD) and monoclonal related membranoproliferative glomerulonephritis (MPGN). Low-grade B-cell lymphoma was associated with two cases. The remaining 16 (59.2%) were documented as monoclonal gammopathy of undetermined significance (MGUS) with two had unrelated histology on renal biopsy (FSGS and membranous nephropathy). Kidney biopsy was performed in 7 (25%) cases only.  Remaining 14 cases were listed other aetiologias for renal disease without kidney biopsy.
Conclusion: Kidney biopsy was not done in half of CKD patients with paraproteinemia (MGUS) to ascertain the association of MG with kidney disease. Kidney biopsy may be considered in cases that would be otherwise labelled as MGUS, as potentially disease altering treatments for MGRS are being withheld.


Biography:
Sally Wilkinson is a basic physician trainee at Toowoomba Hospital. She is passionate about research involving chronic kidney disease especially the relation between cancer and CKD. She propose to pursue her advance traineeship in both Nephrology and Onchology

PERSONALISED IMMUNOLOGY IN THE MANAGEMENT OF COMPLEX AUTOIMMUNITY

P PURI1, G WALTERS1,3, K GIBSON1, A COOK2, D FULCHER3, C VINUESA2,3, SJIANG1,2,3
1The Canberra Hospital , Canberra City., Australia, 2Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Canberra City , Australia, 3Centre for Personalised Immunology, NHMRC Centre for Research Excellence, Canberra city,  Australia

A 72-year-old male presented with severe hypophosphatemia, hypokalaemia and hypomagnesaemia associated with recurrent pathological fractures. His background included a steroid-dependant eosinophilia-associated autoimmune disease (EAAD), associated with hypogammaglobulinaemia. Investigations demonstrated hyperphosphaturia (85mmol/24 hours) with normal renal function, parathyroid hormone (PTH) and 25- and 1,25-dihydroxycholecalciferol levels. Serum fibroblast growth factor (FGF23) levels ranged between 56 – 900ng/L suggestive of tumour-induced osteomalacia (TIO). Venous sampling and DOTATATE CT-PET were non-diagnostic. Aside from persistent eosinophilia, autoimmune serology was negative.
Treatment: Phosphate was corrected with parenteral phosphate (dose 80mmol/12hr) and calcitriol (3ug/daily). The patient was trialled on methotrexate, hydroxyurea, and secukinumab with limited clinical efficacy.  Despite normalization of eosinophilia by mepolizumab he remained prednisolone dependant requiring 15mg/day to maintain EAAD remission. Due to the severity of his autoimmune disease and steroid dependency, the patient underwent immunophenotyping and exome sequencing through the Canberra Hospital Glomerulonephritis clinic and ANU Centre for Personalised Immunology. Immunophenotyping demonstrated an increase in CD8+ T cells (61.1%vs 36.8% (58.5-63.8) of CD3+ in healthy controls (HC) p=0.005) and T regulatory cells (Tregs) (CD3+CD4+CD25+CD127-) (17.05 vs 5.54 (4.65-5.54) HC, p=<0.0001). CD8+ subsets demonstrated reduced naïve CD8+ (CD3+CD8+CCR7+CD45RA+) (8.5% vs 46.7 (37.8-58.8) p=0.0009) and expansion of CD8+ TEMRA (CD3+CD8+CCR7-CD45RA+) (66.4% vs 13.9 (11.1 – 19.6), p<0.0001) suggesting a state of chronic activation. We commenced tacrolimus aiming levels between 5-7ng/ml to control CD8+ activity. 2 months after initiation the patient was tapering on 9mg prednisolone with no inflammatory arthritis. Repeat immunophenotyping demonstrated a decline in Tregs (17.05 to 8.5% post-treatment) and CD8+ TEMRA (66.4 – 57.2% post-treatment).
Discussion: Immunophenotyping and genome sequencing may assist in individualising aetiology, pathophysiology and therefore therapeutic targets in difficult to treat or undifferentiated autoimmune disease.


Biography:
I am a first year Renal trainee at the Canberra hospital. I have an interest in renal immunology and transplantation. I hope to undertake more research in these fields over the course of my training both in a lab and clinical setting.

IMPACT OF BELATACEPT CONVERSION ON KIDNEY TRANSPLANT FUNCTION, HISTOLOGY AND GENE EXPRESSION

P SANGHI1, P HALLORAN2, D KUMAR1, J REEVE2, M LEVY1, A SHARMA1, H FATTAH1, P KIMBALL1, HD MASSEY1,  AL KING1, G GUPTA1

1Virginia Commonwealth University, Richmond, USA; 2Alberta Transplant Applied Genomics Center, Edmonton, Canada

Background: Belatacept (bela) might be an alternative to Calcineurin Inhibitors (CNI) in order to avoid nephrotoxicity. In this study we assessed the impact of bela conversion in a cohort of kidney transplant patients (KT).

Methods: EBV seropositive adult patients were converted to bela from tacrolimus, as per our protocol, for biopsy proven interstitial fibrosis/tubular atrophy. A majority of patients (N=29; 71%) underwent a surveillance biopsy within 6 months of conversion. A subset of pre- and post-conversion biopsies underwent transcriptome analysis (N=20) using the Molecular microscope system (MMDx).

Results
: Forty-one (mean age=45 years) patients were switched to bela at a median of 6 months post-KT. Many were sensitized (cPRA range=29-100%); regrafts (22%); had delayed graft function (56%) and had a history of acute rejection (22%). Death-censored graft survival was 88% at a mean follow-up of 3.4 years post-conversion. Of the five allograft failures, three were lost partially due to acute rejection. The median time to conversion was 5.6 months and median time on bela was 17months.

Renal function improved from an eGFR of 31.6±15.8ml/min/1.73m2 to 38.7±17.7ml/min/1.73m2 at 3 months (p=0.003) post conversion. This improvement was sustained with an eGFR of 40.7±15.8ml/min/1.73m2   at most recent follow-up (p<0.001). Paired pre- and post-conversion histologic analysis did not reveal any worsening of microvascular inflammation or chronicity. Similarly, MMDx analysis did not reveal any significant changes in markers of acute kidney injury.

Conclusions
: In this study we demonstrate that belatacept conversion might be safe for KT patients, including the high-immunologic risk group. Since renal function improved early and then stayed stable, it is possible that the primary reason for improvement is vasomotor, rather than a true change in fibrogenesis.

FATHERHOOD WHILE RECEIVING DIALYSIS AND AFTER KIDNEY TRANSPLANTATION: ANALYSIS OF THE AUSTRALIAN AND NEW ZEALAND DIALYSIS AND TRANSPLANTATION (ANZDATA) REGISTRY 1970–2014

A FITZPATRICK1, A GULYANI2, P CLAYTON1,2,3, SP MCDONALD, S JESUDASON1,3

1Central and Northern Adelaide Renal and Transplantation Services (CNARTS), Royal Adelaide Hospital, Adelaide, South Australia; 2ANZDATA and ANZOD Registry, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, South Australia; 3School of Medicine, University of Adelaide, Adelaide, South Australia

Aim: To describe parenthood outcomes for fathers receiving renal replacement therapy (RRT).

Background: The effects of paternal uraemia, immunosuppression and comorbidity may affect offspring. Outcome data for pregnancies fathered by dialysed versus transplanted men is minimal.

Methods: Parenthood data reported to ANZDATA (1970-2014) was analysed using the Student’s t-test, chi-squared/Fisher’s exact test, and random effects linear and logistic regression.

Results: Overall, 872 men had 1248 conception events reported. Renal replacement therapy modality at conception was transplant for 925 (74%), haemodialysis for 275 (22%) and peritoneal dialysis for 48 (4%) of events. Transplanted fathers had mean±SD preconception serum creatinine of 155.9±56.6 umol/L. The parenthood data form introduced in 2001 improved data collection. After 2001, 529 parenthood events were reported. Gestational age (GA) was missing for only 2.5% and birthweight (BW) for 38.6% of reports.

The live birth rate (LBR) was 96.1% (1199 births) and similar between transplanted and dialysed men (97.9% vs. 96.2%, p=ns). The LBR for pregnancies reaching >20 weeks (where GA was known) was 99.7% for transplant fathers and 99.3% for dialysed fathers, comparable to national rates (99.3%, AIHW 2014). The mean±SD GA was 38.1±2.7 weeks, and BW 3.36±0.66kg.  Treatment modality, time post-transplant and dialysis duration had no significant association with fetal outcome. Paternal mycophenolate use (n=358 events) was not associated with abnormal foetal morphology (OR 0.43, 95%CI 0.08, 2.37), and had no effect on LBR (OR 1.35, 95%CI 0.64, 2.84), GA (0.60 weeks, 95% CI 0.34, 1.54) or BW (85.6grams, 95%CI -59.6, 230.7).

Conclusions: A large number of fatherhood events have been reported to ANZDATA, facilitated by specific parenthood forms. No difference in fetal outcomes was observed between transplanted or dialysed fathers.

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