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Transplantation (all articles)

Cohort Study: High Rate of Preventable Adverse Events in Surgical Inpatients

16 Nov, 2024 | 17:29h | UTC

Background: Adverse events during hospital admissions, particularly in surgical settings, remain a significant cause of patient harm despite efforts to improve patient safety since the “To Err is Human” report. Advances in surgical techniques and patient care necessitate an updated assessment of the current state of perioperative safety.

Objective: To estimate the frequency, severity, and preventability of adverse events associated with perioperative care in surgical inpatients and to identify the settings and healthcare professionals involved.

Methods: A multicenter retrospective cohort study was conducted across 11 US hospitals in Massachusetts. A weighted random sample of 1,009 patients was selected from 64,121 adults admitted for surgery in 2018. Trained nurses reviewed electronic health records to identify adverse events, which were then adjudicated by physicians. Adverse events were classified by type, severity, preventability, setting, and professions involved.

Results: Adverse events occurred in 38.0% of patients (95% CI, 32.6–43.4%), with major adverse events in 15.9% (12.7–19.0%). Among 593 adverse events identified, 59.5% were potentially preventable, and 20.7% were definitely or probably preventable. The most common events were surgery-related (49.3%), adverse drug events (26.6%), healthcare-associated infections (12.4%), and patient care events (11.2%). Adverse events most frequently occurred in general care units (48.8%) and involved attending physicians (89.5%) and nurses (58.9%).

Conclusions: More than one-third of surgical inpatients experienced adverse events, with nearly half classified as major and most potentially preventable. These findings highlight the critical need for ongoing improvement in patient safety throughout perioperative care involving all healthcare professionals.

Implications for Practice: Healthcare providers should enhance patient safety protocols across all perioperative settings, not just in operating rooms. Emphasis should be placed on preventing surgery-related complications, adverse drug events, and healthcare-associated infections by fostering teamwork and continuous monitoring.

Study Strengths and Limitations: Strengths include a comprehensive review of medical records and systematic classification of adverse events by trained professionals. Limitations involve the study’s confinement to Massachusetts hospitals in 2018, potential variability in documentation practices, and limited sample size affecting generalizability and specialty-specific estimates.

Future Research: Further studies are needed to assess adverse event rates in diverse geographic locations and healthcare systems, explore effective interventions to reduce preventable harm, and evaluate long-term trends in surgical patient safety.

Reference: Duclos A, Frits ML, Iannaccone C, Lipsitz SR, Cooper Z, Weissman JS, Bates DW. Safety of inpatient care in surgical settings: cohort study. BMJ. 2024; DOI: http://doi.org/10.1136/bmj-2024-080480

 

Review: Lung Transplantation

16 Nov, 2024 | 13:33h | UTC

Introduction: Lung transplantation has progressed from experimental to standard therapy for life-threatening lung diseases, offering improved survival and quality of life. Challenges include primary graft dysfunction, chronic lung allograft dysfunction (CLAD), infections, and long-term immunosuppression effects. This review highlights current practices, developments, and opportunities to enhance this transformative therapy.

Key Recommendations

  1. Candidate Selection: Selection criteria have shifted from strict contraindications to a holistic approach emphasizing physiologic age, frailty, and recoverability. Early referral and multidisciplinary assessment are recommended to address barriers and optimize outcomes.
  2. Donor-Lung Utilization: Extended-criteria donors, including older donors and those with smoking histories, are increasingly used. Ex vivo lung perfusion allows detailed lung assessment and reconditioning, while antiviral therapies enable transplantation of lungs from hepatitis C-positive donors.
  3. Lung Allocation: Urgency-weighted scores prioritize factors like medical urgency and post-transplant survival. Recent updates include biologic disadvantages, patient access, and logistical efficiency to improve fairness and outcomes.
  4. Surgical Techniques: Bilateral sequential lung transplantation is standard, with ECMO replacing cardiopulmonary bypass in many cases. Surgical approaches are tailored to individual needs, with options like volume reduction or lobectomy for size mismatches.
  5. Postoperative Management: Primary graft dysfunction affects up to 25% of recipients and is a major early complication. Preventive strategies, ECMO support, and infection management are critical. Attention to airway complications and acute kidney injury further improves recovery.
  6. Immunosuppression: Maintenance therapy typically includes a calcineurin inhibitor, glucocorticoid, and cell-cycle inhibitor. Induction therapy is individualized. Ongoing studies are exploring adjunct therapies like mTOR inhibitors and inhaled immunosuppressants to prevent CLAD.
  7. Management of ALAD and CLAD: Early detection and treatment of acute lung allograft dysfunction are essential. CLAD, affecting half of recipients within 5 years, remains a major challenge. Current therapies slow progression, but further research is needed for targeted prevention and treatment.
  8. Infections: Infections remain a leading cause of morbidity and mortality. Prophylaxis against cytomegalovirus, fungal pathogens, and community-acquired viruses is essential to minimize complications and reduce CLAD risk.
  9. Cancer Risk: Post-transplant cancer risk is elevated due to immunosuppression. Lung cancer and post-transplant lymphoproliferative disease are the most common malignancies, emphasizing the need for routine surveillance and early intervention.
  10. Long-Term Outcomes: Median survival remains limited at 6.7 years. Efforts focus on improving long-term outcomes by balancing graft function maintenance with minimizing adverse effects of immunosuppression. Collaborative research aims to refine diagnostics, personalize therapies, and address CLAD mechanisms.

Conclusion: Enhanced donor utilization, tailored candidate selection, refined perioperative care, and robust long-term monitoring are pivotal to advancing lung transplantation. Ongoing research and collaboration are critical to overcoming challenges like CLAD, improving survival, and enhancing patient quality of life.

Reference: Christie JD, et al. Lung Transplantation. New England Journal of Medicine. 2024. DOI: http://doi.org/10.1056/NEJMra2401039

 

Management of Ascites in Cirrhosis: Key Recommendations from the British Society of Gastroenterology Guidelines

12 Oct, 2024 | 18:23h | UTC

Introduction: Ascites, the pathological accumulation of fluid within the peritoneal cavity, is a common and serious complication of cirrhosis, indicating advanced liver disease and portending increased morbidity and mortality. Recognizing the need for updated clinical guidance, the British Society of Gastroenterology (BSG), in collaboration with the British Association for the Study of the Liver (BASL), has issued comprehensive guidelines. These aim to standardize the diagnosis and management of ascites in cirrhotic patients, incorporating recent advances to optimize patient outcomes.

Key Recommendations:

  1. Diagnostic Paracentesis: It is strongly recommended that all patients with new-onset ascites undergo diagnostic paracentesis to measure total protein concentration and calculate the serum-ascites albumin gradient (SAAG). (Quality of evidence: moderate; Recommendation: strong)
  2. Spontaneous Bacterial Peritonitis (SBP): Prompt diagnostic paracentesis should be performed in hospitalized patients with ascites, especially those with gastrointestinal bleeding or signs of infection, to rule out SBP. An ascitic neutrophil count >250/mm³ confirms SBP, necessitating immediate empirical antibiotic therapy tailored to local resistance patterns. (Quality of evidence: moderate; Recommendation: strong)
  3. Dietary Salt Restriction: Patients should restrict dietary sodium intake to no more than 5–6.5 grams per day (87–113 mmol), equivalent to a no-added-salt diet, to manage fluid accumulation effectively. (Quality of evidence: moderate; Recommendation: strong)
  4. Diuretic Therapy: For initial moderate ascites, spironolactone monotherapy is recommended. In cases of recurrent severe ascites, combination therapy with spironolactone and furosemide is advised. Regular monitoring for adverse events such as electrolyte imbalances and renal impairment is essential. (Quality of evidence: moderate; Recommendation: strong)
  5. Large Volume Paracentesis (LVP): LVP is a safe and effective treatment for refractory ascites. Informed consent is required, and routine coagulation studies or prophylactic blood product infusions before the procedure are not recommended. (Quality of evidence: moderate; Recommendation: strong)
  6. Use of Human Albumin Solution (HAS): After LVP exceeding 5 liters, infusion of HAS at 8 grams per liter of ascites removed is strongly recommended to prevent circulatory dysfunction. (Quality of evidence: high; Recommendation: strong)
  7. Transjugular Intrahepatic Portosystemic Shunt (TIPSS): TIPSS should be considered for patients with refractory ascites not responding to medical therapy, with caution exercised in patients over 70 years or those with significant comorbidities. (Quality of evidence: high; Recommendation: strong)
  8. Non-Selective Beta-Blockers (NSBBs): The presence of refractory ascites is not a contraindication for NSBB therapy. Patients should be closely monitored, and dose adjustments made in cases of hypotension or renal dysfunction. (Quality of evidence: moderate; Recommendation: strong)
  9. Palliative Care: Patients unsuitable for liver transplantation should be offered palliative care referral to focus on symptom management and quality of life improvement. Alternative interventions for refractory ascites may also be considered. (Quality of evidence: weak; Recommendation: strong)

Conclusion: Implementation of these evidence-based guidelines is expected to enhance patient care by promoting early diagnosis, preventing complications, and standardizing management strategies for ascites in cirrhosis. Adherence to these recommendations can improve clinical outcomes, reduce hospitalizations, and enhance the quality of life for affected patients.

Reference: Aithal GP, Palaniyappan N, China L, et al. Guidelines on the management of ascites in cirrhosis. Gut. 2021;70(1):9–29. DOI: http://doi.org/10.1136/gutjnl-2020-321790

 

Phase 2 RCT: Axatilimab Demonstrates Efficacy in Refractory Chronic GVHD by Targeting CSF1R-Dependent Macrophages

19 Sep, 2024 | 16:05h | UTC

Background: Chronic graft-versus-host disease (GVHD) is a significant long-term complication of allogeneic hematopoietic stem-cell transplantation, affecting approximately half of recipients and leading to substantial morbidity and mortality. Standard therapies often fail to induce durable responses in patients with refractory or recurrent disease. CSF1R-dependent monocytes and macrophages are key mediators of chronic GVHD, contributing to inflammation and fibrosis. Axatilimab, a CSF1R-blocking antibody, has shown promising activity in early studies.

Objective: To evaluate the efficacy and safety of axatilimab at three different doses in patients with recurrent or refractory chronic GVHD.

Methods: In this phase 2, multinational, randomized study (AGAVE-201), 241 patients aged ≥2 years with active chronic GVHD after at least two prior systemic therapies were randomized 1:1:1 to receive intravenous axatilimab at 0.3 mg/kg every 2 weeks (n=80), 1 mg/kg every 2 weeks (n=81), or 3 mg/kg every 4 weeks (n=80). Randomization was stratified by chronic GVHD severity and prior use of FDA-approved therapies (ibrutinib, ruxolitinib, or belumosudil). The primary endpoint was overall response rate (complete or partial response) within the first six cycles. The key secondary endpoint was a patient-reported reduction in symptom burden, defined as a decrease of more than 5 points on the modified Lee Symptom Scale (range 0–100).

Results: The overall response rate was 74% (95% CI, 63%–83%) in the 0.3 mg/kg group, 67% (95% CI, 55%–77%) in the 1 mg/kg group, and 50% (95% CI, 39%–61%) in the 3 mg/kg group, exceeding the predefined efficacy threshold in all groups. A clinically meaningful reduction in symptom burden was reported in 60%, 69%, and 41% of patients in the respective dose groups. Median time to response was less than 2 months across all groups. Organ-specific responses were observed in all affected organs, including skin, lungs, joints, and fascia.

The most common adverse events were dose-dependent transient laboratory abnormalities related to CSF1R blockade, such as elevations in liver enzymes and creatine kinase, which were not associated with clinical symptoms or end-organ damage. Periorbital edema occurred more frequently at higher doses. Adverse events leading to discontinuation occurred in 6% of patients in the 0.3 mg/kg group, 22% in the 1 mg/kg group, and 18% in the 3 mg/kg group. Serious infections were reported but were not dose-dependent.

Conclusions: Axatilimab demonstrated significant efficacy in patients with heavily pretreated recurrent or refractory chronic GVHD, with the highest response rates and best tolerability observed at the lowest dose tested (0.3 mg/kg every 2 weeks). Targeting CSF1R-dependent monocytes and macrophages may represent a novel therapeutic strategy in chronic GVHD.

Implications for Practice: Axatilimab offers a potential new treatment option for patients with chronic GVHD refractory to standard therapies, including those who have failed prior FDA-approved treatments. Clinicians should consider axatilimab as a therapeutic option while monitoring for transient laboratory abnormalities associated with CSF1R blockade. The lower dose appears to provide optimal efficacy with fewer adverse events.

Study Strengths and Limitations: Strengths include the randomized, multinational design and inclusion of patients with severe, refractory chronic GVHD who had received multiple prior therapies. Limitations include the lack of a comparator group, which may introduce outcome-reporting bias, and the small sizes of subgroups, limiting the generalizability of certain findings.

Future Research: Further studies are needed to confirm these results, assess long-term outcomes, and explore axatilimab in earlier lines of therapy and in combination with other treatments. Investigations into the use of axatilimab in other autoimmune diseases characterized by CSF1R-driven macrophage-mediated inflammation and fibrosis are also warranted.

Reference: Wolff D, Cutler C, Lee SJ, Pusic I, Bittencourt H, White J, Hamadani M, et al. Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2024. DOI: http://doi.org/10.1056/NEJMoa2401537

 

RCT: Hypothermic Oxygenated Perfusion Trends Toward Lower Primary Graft Dysfunction in Heart Transplantation – The Lancet

17 Aug, 2024 | 19:38h | UTC

Study Design and Population: This randomized, controlled, open-label, multicenter clinical trial evaluated the safety and efficacy of hypothermic oxygenated machine perfusion (HOPE) compared to static cold storage (SCS) in preserving donor hearts for transplantation. Conducted across 15 transplant centers in eight European countries, the study enrolled 229 adult heart transplant candidates between November 2020 and May 2023. The trial included 204 patients who received a transplant and met the study’s inclusion and exclusion criteria.

Main Findings: The primary composite endpoint, including cardiac-related death, graft dysfunction, and rejection within 30 days post-transplant, occurred in 19% of patients in the HOPE group compared to 30% in the SCS group, reflecting a 44% risk reduction (HR 0.56, 95% CI 0.32–0.99, p=0.059). Notably, primary graft dysfunction was significantly lower in the HOPE group (11% vs. 28%, RR 0.39, 95% CI 0.20–0.73). The incidence of major adverse cardiac transplant events was also reduced with HOPE (18% vs. 32%, RR 0.56, 95% CI 0.34–0.92).

Implications for Practice: HOPE showed a potential clinical benefit by reducing the incidence of primary graft dysfunction and major adverse cardiac events after heart transplantation. Although the primary endpoint was not statistically significant, the observed risk reductions suggest that HOPE could improve outcomes in heart transplantation. Further research is needed to confirm these findings and optimize donor heart preservation strategies.

Reference: Rega, F., Lebreton, G., Para, M., Michel, S., Schramm, R., Begot, E., et al. (2024). Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial. The Lancet, 404(10453), 670-682. DOI: https://doi.org/10.1016/S0140-6736(24)01078-X.

 

RCT | Exploring the impact of total pancreatectomy with islet autotransplantation to reduce postoperative complications

8 Aug, 2023 | 13:25h | UTC

Total Pancreatectomy With Islet Autotransplantation as an Alternative to High-risk Pancreatojejunostomy After Pancreaticoduodenectomy: A Prospective Randomized Trial – Annals of Surgery

 

AAP Policy Statement | Pediatric organ donation and transplantation: across the care continuum

1 Aug, 2023 | 14:26h | UTC

Pediatric Organ Donation and Transplantation: Across the Care Continuum – Pediatrics

News Release: Policy underscores role of medical home in pediatric organ donation, transplantation – AAP News

Commentary: Pediatric Organ Donation and Transplantation: What Primary Care Providers and Families Should Know – AAP Journal Blog

 

Nonrandomized Controlled Trial | Long-term survival of 80% in selected colorectal cancer patients post liver transplant

1 Aug, 2023 | 14:20h | UTC

Long-Term Survival, Prognostic Factors, and Selection of Patients With Colorectal Cancer for Liver Transplant: A Nonrandomized Controlled Trial – JAMA Surgery (link to abstract – $ for full-text)

 

Commentary on Twitter

 

Study | Left ventricular dysfunction in brain-dead heart donors – incidence, reversibility, and implications

31 Jul, 2023 | 14:09h | UTC

Left Ventricular Dysfunction Associated With Brain Death: Results From the Donor Heart Study – Circulation (free for a limited period)

 

Cohort Study | Proton pump inhibitor use linked to increased fatigue in kidney transplant recipients

26 Jul, 2023 | 13:21h | UTC

Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients: Results From the TransplantLines Biobank and Cohort Study – American Journal of Kidney Diseases

 

Commentary on Twitter

 

AHA Statement | Indications, evaluation, and outcomes for dual heart-kidney and heart-liver transplantation

14 Jul, 2023 | 12:51h | UTC

Dual-Organ Transplantation: Indications, Evaluation, and Outcomes for Heart-Kidney and Heart-Liver Transplantation: A Scientific Statement From the American Heart Association – Circulation

 

Guideline | Acute liver failure

10 Jul, 2023 | 13:59h | UTC

Acute Liver Failure Guidelines – The American Journal of Gastroenterology

Related:

EASL Clinical Practice Guidelines on acute-on-chronic liver failure – Journal of Hepatology

Guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU

Acute-on-chronic liver failure: far to go—a review – Critical Care

 

Canadian Guidance | Deceased organ and tissue donation after medical assistance in dying

10 Jul, 2023 | 13:41h | UTC

Deceased organ and tissue donation after medical assistance in dying: 2023 updated guidance for policy – Canadian Medical Association Journal

Commentary: What happens to the organs of people who choose medically assisted deaths? – CTV News

 

RCT | Substituting saline with balanced crystalloid solution reduces delayed graft function in kidney transplantation

30 Jun, 2023 | 14:56h | UTC

Summary: The BEST-Fluids study was a pragmatic, multicentre, double-blind, randomized controlled trial carried out across 16 hospitals in Australia and New Zealand, aimed at comparing the use of balanced crystalloid solution (Plasma-Lyte 148) and saline in deceased donor kidney transplantation. The sample size comprised of 808 participants, who were either adults or children of any age, with the primary outcome defined as delayed graft function (DGF) occurring within 7 days post-transplantation.

Findings from the trial revealed that the balanced crystalloid group experienced less DGF than the saline group, with 121 out of 404 participants (30%) and 160 out of 403 participants (40%), respectively. This result yields an adjusted relative risk of 0.74 and an adjusted risk difference of 10.1%.

The study suggests that balanced crystalloid solution significantly reduces the incidence of DGF compared to saline. As no significant safety concerns were raised during the trial, the researchers recommend the use of balanced crystalloid solution as the standard-of-care intravenous fluid in deceased donor kidney transplantation. However, the study doesn’t indicate any significant differences in graft failure or mortality rates, which calls for further research.

Article: Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial – The Lancet (free registration required)

 

Liver Transplantation 2023 | Status report, current and future challenges

29 Jun, 2023 | 13:50h | UTC

Liver Transplantation 2023: Status Report, Current and Future Challenges – Clinical Gastroenterology and Hepatology

 

RCT | Cyclophosphamide-based regimen enhances GVHD-free survival after hematopoietic stem-cell transplantation

27 Jun, 2023 | 13:54h | UTC

Summary: The article details a phase 3 trial comparing the efficacy of two graft-versus-host disease (GVHD) prophylactic regimens in hematologic cancer patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). The experimental group received cyclophosphamide–tacrolimus–mycophenolate mofetil, and the standard group received tacrolimus–methotrexate. The patients, a total of 431, underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched unrelated donor.

The primary end point was GVHD-free, relapse-free survival at 1 year. Results indicated a significantly higher incidence of this outcome in the experimental group (hazard ratio, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P=0.001). At 1 year, adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) in the experimental group, compared to 34.9% (95% CI, 28.6 to 41.3) in the standard group.

Notably, patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall survival, disease-free survival, relapse, transplantation-related death, and engraftment did not show a substantial difference between the groups. These results suggest that cyclophosphamide–tacrolimus–mycophenolate mofetil may offer a more effective prophylaxis against GVHD in HSCT patients.

Article: Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis – New England Journal of Medicine (link to abstract – $ for full-text)

News Release: Study Sets New Standard for Graft-Versus-Host Disease Prevention After Stem Cell Transplant – Johns Hopkins Medicine

 

Commentary on Twitter

 

Consensus Paper | Primary prophylaxis of invasive fungal diseases in patients with hematological malignancies

23 Jun, 2023 | 13:23h | UTC

Primary prophylaxis of invasive fungal diseases in patients with haematological malignancies: 2022 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) – Journal of Antimicrobial Chemotherapy

 

Review | Acute graft-versus-host disease

14 Jun, 2023 | 14:20h | UTC

Acute graft-versus-host disease – Nature Reviews Disease Primers (if the link is paywalled, try this one)

 

Commentary on Twitter

 

RCT | No change in delayed graft function with normothermic perfusion vs. cold storage in kidney transplants

13 Jun, 2023 | 14:00h | UTC

Normothermic machine perfusion versus static cold storage in donation after circulatory death kidney transplantation: a randomized controlled trial – Nature Medicine

 

Commentary on Twitter

 

Review | Challenges and opportunities in antimicrobial stewardship among hematopoietic stem cell transplant and oncology patients

13 Jun, 2023 | 13:55h | UTC

Challenges and Opportunities in Antimicrobial Stewardship among Hematopoietic Stem Cell Transplant and Oncology Patients – Antibiotics

 

RCT | Noninferior survival rates with hearts donated after circulatory death versus brain death

12 Jun, 2023 | 13:57h | UTC

Transplantation Outcomes with Donor Hearts after Circulatory Death – New England Journal of Medicine (link to abstract – $ for full-text)

Video summary: Outcomes with Donor Hearts after Circulatory Death | NEJM

News Release: Multicenter Trial Finds Using Circulatory Death Donors is Safe and Effective for Heart Transplantation – Northwestern Medicine

Commentary: Transplantation Outcomes With Donor Hearts After Circulatory Death – American College of Cardiology

 

Commentary on Twitter

 

RCT | Letermovir demonstrates noninferiority to valganciclovir for CMV prophylaxis in kidney transplantation

12 Jun, 2023 | 13:38h | UTC

Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients: A Randomized Clinical Trial – JAMA (free for a limited period)

Editorial: A New Antiviral Option for Cytomegalovirus Prevention After Kidney Transplant – JAMA (free for a limited period)

See also: Visual Abstract

Commentary: Newly approved antiviral is promising alternative against cytomegalovirus illness in kidney transplants – CIDRAP

 

Consensus Paper | Organ donation in the surgical ICU

1 Jun, 2023 | 12:12h | UTC

Organ donation in the surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document – Trauma Surgery & Acute Care Open

 

ISHLT Guideline | Mechanical circulatory support

29 May, 2023 | 10:40h | UTC

The 2023 International Society for Heart and Lung Transplantation Guidelines for Mechanical Circulatory Support: A 10- Year Update – The Journal of Heart and Lung Transplantation

 

ISHLT Guidelines for the care of heart transplant recipients

3 May, 2023 | 15:09h | UTC

The International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients – The Journal of Heart and Lung Transplantation

 

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