Publications by authors named "Oscar K Serrano"

56 Publications

Effect of Blood Product Resuscitation on the Pharmacokinetics of Ampicillin-Sulbactam during Orthotopic Liver Transplantation.

Surg Infect (Larchmt) 2021 Nov 24. Epub 2021 Nov 24.

Center for Anti-Infective Research and Development, Hartford Hospital, Harford, Connecticut, USA.

Ampicillin-sulbactam is a piperacillin-tazobactam-sparing alternative antibiotic administered as surgical prophylaxis during orthotopic liver transplant (OLT), but limited data are available describing its pharmacokinetics and impact of blood product resuscitation. The purpose of this study was to determine the intra-operative pharmacokinetics of ampicillin-sulbactam in patients during OLT and evaluate the effects of blood resuscitation on exposure. This was a pharmacokinetic study in 10 OLT patients receiving ampicillin-sulbactam surgical prophylaxis. A 5,000-patient Monte Carlo simulation was conducted to identify optimal ampicillin-sulbactam regimens. Linear regression assessed association between blood product administration and ampicillin exposures. Ampicillin and sulbactam concentrations best fitted two-compartment models. Mean ampicillin pharmacokinetic parameters were central compartment volume (V): 6.9 ± 2.0 L, clearance (CL): 26.6 ± 18.4 L/h, and inter-compartmental rate constants (k and k): 4.8 ± 2.6 and 2.3 ± 1.4 h. Sulbactam pharmacokinetic parameters were V: 8.1 ± 2.7 L, CL: 26.1 ± 7.4 L/h, k and k: 4.9 ± 1.0 and 2.8 ± 1.1 h. Participants received between 500 and 23,642 mL of total blood product. No statistical relations were observed between blood product administration and exposures ( 0.00-0.26). Ampicillin-sulbactam 2/1 g every two hours and 2/1 g bolus followed by 6/3 g continuous infusion provided acceptable probability of target attainment up to minimum inhibitory concentrations (MICs) of 16 and 32 mcg/mL, respectively. High and frequent ampicillin-sulbactam doses are required to maintain 100% T > MIC at relevant MICs during OLT and no impact of blood product resuscitation was observed on ampicillin exposure. These are the first data available to guide ampicillin-sulbactam dosing in patients undergoing OLT.
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http://dx.doi.org/10.1089/sur.2021.218DOI Listing
November 2021

Survival benefit of the homologous kidney allograft in simultaneous pancreas-kidney transplants and its potential protective role.

Clin Transplant 2021 Nov 30;35(11):e14462. Epub 2021 Oct 30.

Division of Transplantation, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.

The superior death-censored graft survival of the pancreas allograft in simultaneous pancreas kidney transplants (SPK) over pancreas alone transplants (PTA) has long been recognized. Using data from the Scientific Registry of Transplant Recipients (SRTR) and a high-volume pancreas transplant program, we investigated the possible protective role of the kidney allograft in SPK transplants. We analyzed 19 043 primary pancreas transplants between 2000 and 2020, including 735 transplants performed at the University of Minnesota. SPK transplants demonstrated a superior death-censored graft survival over pancreas after kidney (PAK) and simultaneous pancreas and living donor kidney (SPLK) transplants, which both demonstrated better survival than PTA transplants. This effect was not affected by mode or duration of renal replacement therapy prior to transplant. Furthermore, we found that HLA match at the B-locus between the prior kidney and current pancreas allografts demonstrated a protective effect (HR .54; 95% confidence interval .29-1.00), with a 2-antigen match demonstrating superior death-censored graft survival to a 1- or 0-antigen match. We propose that a homologous kidney allograft in SPK transplants affords protection to the pancreas allograft-likely through a combination of better surveillance for rejection and direct immunoprotection offered by the same-donor kidney.
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http://dx.doi.org/10.1111/ctr.14462DOI Listing
November 2021

Access to liver transplantation for minority populations in the United States.

Curr Opin Organ Transplant 2021 10;26(5):508-512

Department of Surgery, University of Connecticut School of Medicine.

Purpose Of Review: Racial disparities in access to liver transplantation have been known since the National Transplant Act of 1980. Since the inception of the Final Rule in 2000, the United Network of Organ Sharing has sought to ensure the equitable distribution of donor livers. Despite several measures aimed to improve access for vulnerable populations, disparities in outcomes are still prevalent throughout the liver transplant (LT) evaluation, while on the waitlist, and after liver transplantation.

Recent Findings: Blacks and Hispanics are underrepresented on the LT list and have an increased waitlist mortality rate compared to Whites. Additionally, Blacks have a significantly higher risk of posttransplant mortality.

Summary: Ongoing efforts are necessary to eliminate inequities in transplant access. Strategies such as policy implementation and increasing diversity in the healthcare workforce may prove efficacious in creating change.
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http://dx.doi.org/10.1097/MOT.0000000000000904DOI Listing
October 2021

Challenging the notion of conflict of interest in transplantation: Barriers at the intersection between innovation and clinical advancement.

Am J Transplant 2021 11 24;21(11):3812-3813. Epub 2021 Jul 24.

University of Iowa Hospitals & Clinics, Iowa City, Iowa, USA.

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http://dx.doi.org/10.1111/ajt.16763DOI Listing
November 2021

Initial experience of bamlanivimab monotherapy use in solid organ transplant recipients.

Transpl Infect Dis 2021 Oct 16;23(5):e13662. Epub 2021 Jun 16.

Department of Transplant and Comprehensive Liver Center, Hartford Hospital, Hartford, CT, USA.

The widespread transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to propagate the coronavirus disease 2019 (COVID-19) pandemic with solid organ transplant (SOT) recipients being an exceptionally vulnerable population for poor outcomes. Treatments for COVID-19 are limited; however, monoclonal antibodies are emerging as a potential therapeutic option to change the trajectory of high-risk patients. This retrospective single center cohort study evaluated the outcomes of SOT recipients with mild to moderate COVID-19 who received bamlanivimab monotherapy. Eighteen SOT recipients (15 kidney, 2 liver, and 1 heart) received the medication between November 9, 2020 and February 10, 2021 with no reported infusion reactions. One patient experienced headache and fatigue following the infusion that resolved within 3 days. Fourteen patients continued their recovery as an outpatient with no further escalation in care. Three patients required hospitalization: two for suspected bacterial pneumonia 9 and 32 days postinfusion, respectively, and one for acute kidney injury 7 days postinfusion. One patient had an emergency room visit for gastrointestinal symptoms 24 days postinfusion. In this small cohort of SOT recipients, bamlanivimab monotherapy appeared to be a well-tolerated option for treatment of mild to moderate COVID-19, but it was not completely effective in preventing hospitalization. One month following the end of this cohort, COVID-19 treatment guidance changed due to the rising prevalence of resistant variants. For this reason, bamlanivimab is now recommended to be used only in combination with etesevimab. Further studies are needed to fully elucidate the role of this therapy in SOT recipients.
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http://dx.doi.org/10.1111/tid.13662DOI Listing
October 2021

Acute Myeloid Leukemia Presenting Less Than 3 Weeks After Living Donor Kidney Transplant: A Case Report.

Transplant Proc 2021 May 20;53(4):1360-1364. Epub 2021 Apr 20.

Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut; Hartford Hospital Transplant and Comprehensive Liver Center, Hartford, Connecticut. Electronic address:

Acute myeloid leukemia (AML) is a rare malignancy with increased incidence in the kidney transplantation (KT) population for which immunosuppression has been implicated as a putative cause. The average time interval from KT to AML development is 5 years. We present the case of a 61-year-old man who was found to have peripheral blood blasts on a postoperative day 20 routine blood draw after an uneventful unrelated living donor kidney transplant. He subsequently had a bone marrow biopsy and next-generation sequencing (NGS)-based molecular testing, which demonstrated AML characterized by SMC1A and TET2 mutations. He received induction chemotherapy followed by hematopoietic cell transplantation (HCT) from the kidney donor, who happened to be matched at one haplotype. At 12 months after his HCT and 15 months after his KT, his AML remained in remission, normal renal function was preserved, no active graft-versus-host disease was present, and immunosuppression was tapering. With full donor-derived hematopoietic chimerism, we expect to be able to discontinue immunosuppression shortly, thereby achieving tolerance. The short time interval between KT and development of AML suggests the malignancy was likely present before KT. Modern NGS-based analysis offers a promising method of identifying transplant candidates with unexplained hematologic abnormalities on pre-KT testing who may benefit from formal hematologic evaluation.
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http://dx.doi.org/10.1016/j.transproceed.2021.03.003DOI Listing
May 2021

Evaluation of a multimodal analgesic regimen on outcomes following laparoscopic living donor nephrectomy.

Clin Transplant 2021 08 19;35(8):e14311. Epub 2021 Apr 19.

Department of Pharmacy Services, Hartford Hospital, Hartford, CT, USA.

Postoperative pain is a significant source of morbidity in patients undergoing living donor nephrectomy (LDN) and a deterrent for candidates. We implemented a standardized multimodal analgesic regimen, which consists of pharmacist-led pre-procedure pain management education, a combination transversus abdominis plane and rectus sheath block performed by the regional anesthesia team, scheduled acetaminophen and gabapentin, and as-needed opioids. This single-center retrospective study evaluated outcomes between patients undergoing LDN who received a multimodal analgesic regimen and a historical cohort. The multimodal cohort had a significantly shorter length of stay (LOS) (days, mean ± SD: 1.8 ± 0.7 vs. 2.6 ± 0.8; p < .001) and a greater proportion who were discharged on postoperative day (POD) 1 (38.6% vs. 1.5%; p < .001). The total morphine milligram equivalents (MME) that patients received during hospitalization were significantly less in the multimodal cohort on POD 0-2. The outpatient MME prescribed through POD 60 was also significantly less in the multimodal cohort (median [IQR]; 180 [150-188] vs. 225 [150-300]; p < .001). The mean patient-reported pain score (PRPS) was significantly lower in the multimodal cohort on POD 0-2. The maximum PRPS was significantly lower on POD 0 (mean ± SD: 7 ± 2 vs. 8 ± 1, respectively; p = .02). This study suggests that our multimodal regimen significantly reduces LOS, PRPS, and opioid requirements and has the potential to improve the donation experience.
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http://dx.doi.org/10.1111/ctr.14311DOI Listing
August 2021

Evaluation of cytomegalovirus prophylaxis in low and intermediate risk kidney transplant recipients receiving lymphocyte-depleting induction.

Transpl Infect Dis 2021 Aug 18;23(4):e13573. Epub 2021 Feb 18.

Department of Pharmacy, Hartford Hospital, Hartford, CT, USA.

Cytomegalovirus (CMV) is a significant cause of morbidity in kidney transplant recipients (KTR). Historically at our institution, KTR with low and intermediate CMV risk received 6 months of valganciclovir if they received lymphocyte depleting induction therapy. This study evaluates choice and duration of CMV prophylaxis based on donor (D) and recipient (R) CMV serostatus and the incidence of post-transplant CMV viremia in low (D-/R-) and intermediate (R+) risk KTR receiving lymphocyte-depleting induction therapy. A protocol utilizing valacyclovir for 3 months for D-/R- and valganciclovir for 3 months for R+ was evaluated. Adult D-/R- and R+ KTR receiving anti-thymocyte globulin, rabbit or alemtuzumab induction from 8/20/2016 to 9/30/2018 were evaluated through 1 year post-transplant. Patients were excluded if their CMV serostatus was D+/R-, received a multi-organ transplant, or received basiliximab. Seventy-seven subjects met the inclusion criteria: 25 D-/R- (4 historic group, 21 experimental group) and 52 R+ (31 historic, 21 experimental). No D-/R- patients experienced CMV viremia. Among the R+ historic and experimental groups, there was no significant difference in viremia incidence (35.5% vs 52.4%; P = .573). Of these cases, the peak viral load was similar between the groups (median [IQR], 67 [<200-444] vs <50 [<50-217]; P = .711), and there was no difference in the incidence of CMV syndrome (16.1% vs 14.3%; P = 1.000) or CMV related hospitalization (12.9% vs 14.3%; P = 1.000). No patient experienced tissue invasive disease. These results suggest limiting valganciclovir exposure may be possible in low and intermediate risk KTR receiving lymphocyte-depleting induction therapy with no apparent impact on CMV-related outcomes.
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http://dx.doi.org/10.1111/tid.13573DOI Listing
August 2021

Donor-Recipient Matching to Optimize the Utility of High Kidney Donor Profile Index Kidneys.

Transplant Proc 2021 Apr 25;53(3):865-871. Epub 2020 Dec 25.

Hartford Hospital Transplant and Comprehensive Liver Center, Hartford, Connecticut; University of Connecticut School of Medicine, Farmington, Connecticut. Electronic address:

Background: In December 2014, the Kidney Donor Profile Index (KDPI) was developed to give more precise information on donor kidney quality. Kidneys with KDPI scores ≥ 85 (K ≥ 85) have been reported to have inferior outcomes to kidneys with KDPI scores < 85.

Methods: After the implementation of the new Kidney Allocation System, we developed a protocol to evaluate K ≥ 85 use. We analyzed the safety and efficacy of our institutional criteria and evaluated post-transplant outcomes. K ≥ 85 recipients were stratified based on their 1-year creatinine and estimated glomerular filtration rates to elucidate characteristics associated with serum creatinine < 1.7 mg/dL or estimated glomerular filtration rates ≤ 45 mL/min/1.73 m.

Results: From December 2014 to December 2019, 304 deceased donor kidney transplants were performed at Hartford Hospital; 58 (19%) were K ≥ 85 with an average KDPI of 91%. There were 4 graft losses; 2 were death censored. Prolonged cold ischemia time and black recipient race were associated with inferior recipient graft function at 1 year.

Conclusions: High KDPI kidney use requires a multifaceted evaluation that takes into account donor and recipient characteristics for an ideal match. We have identified several characteristics that may predict optimal post-transplant kidney function.
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http://dx.doi.org/10.1016/j.transproceed.2020.10.040DOI Listing
April 2021

Impact of Intraoperative Cell Salvage on Concentrations of Antibiotics Used for Surgical Prophylaxis.

Antimicrob Agents Chemother 2020 11 17;64(12). Epub 2020 Nov 17.

Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA

Intraoperative cell salvage (IOCS) is used to administer autologous blood lost during surgery. We studied antibiotic disposition through an IOCS system for vancomycin, piperacillin, ampicillin, and cefazolin. Only 2% ± 1% of antibiotic inoculated in whole blood was recovered in the IOCS reinfusion bag, whereas 97% ± 17% was found in the waste. These observations were confirmed for ampicillin in two patients undergoing liver transplantation. Studies measuring the impact of IOCS on perioperative antibiotic concentrations are warranted.
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http://dx.doi.org/10.1128/AAC.01725-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674051PMC
November 2020

Getting back to work: A framework and pivot plan to resume elective surgery and procedures after COVID-19.

Surg Open Sci 2021 Apr 22;4:12-18. Epub 2020 Oct 22.

Hartford HealthCare, Hartford, CT.

Introduction: The COVID-19 pandemic has compelled a majority of hospital systems to reduce surgical and procedural volumes in an attempt to preserve resources. Elective surgery and procedures resumption has proven to be a calculated risk between COVID-19 exposure and resource depletion and patient morbidity and mortality from surgical deferral.

Methods: Within a few days of halting elective surgery and procedures, our 7-hospital (2427 in-patient beds, 26,647 inpatient surgeries) healthcare system developed a multidisciplinary Pivot Plan with the primary outcome of a phased resumption of elective surgery and procedures. The plan entailed the integration of our electronic medical record, order entry automatization, perioperative staff utilization, partnering with primary care providers, and a stepwise COVID-19 testing algorithm based on a predetermined hierarchy of case acuity and timeliness of patient care.

Results: The Pivot Plan was instituted on May 10, 2020. Since then, 22,624 patients have been tested for COVID-19 in anticipation of an elective surgery and procedures; 140 (0.62%) tested positive for COVID-19 and had their procedure deferred. As our testing capability has increased, we have been able to increase our added elective surgery and procedures capacity from 13 cases per day to 531 cases per day. In turn, we have seen the case volume increase by 52%.

Conclusion: Our academic healthcare system located in one of the initial COVID-19 hotspots in the United States has successfully resumed elective surgery and procedures in part due to a receptive and supportive culture based upon nimbleness, agility, and rapid integration of multiple resources from a cohort of diverse disciplines applied to the perioperative services workflow.
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http://dx.doi.org/10.1016/j.sopen.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578777PMC
April 2021

Opioid Avoidance in Liver Transplant Recipients: Reduction in Postoperative Opioid Use Through a Multidisciplinary Multimodal Approach.

Liver Transpl 2020 10 31;26(10):1254-1262. Epub 2020 Aug 31.

Department of Transplant, Hartford Hospital, Hartford, CT.

The prevalence of substance use disorder in the liver transplantation (LT) population makes postoperative pain management challenging. We report our initial experience with a novel, comprehensive, multidisciplinary opioid avoidance pathway in 13 LT recipients between January 2018 and September 2019. Patients received comprehensive pre-LT education on postoperative opioid avoidance by the surgeon, pharmacist, and psychologist at the time of listing. Immediately after LT, patients received a continuous incisional ropivacaine infusion, ketamine, acetaminophen, and gabapentin as standard nonopioid medications; rescue opioids were used as needed. We compared outcomes with a historical cohort of 27 LT recipients transplanted between August 2016 and January 2018 managed primarily with opioids. On average, opioid avoidance patients used 92% fewer median (interquartile range [IQR]) morphine milligram equivalents (MMEs) versus the historical cohort (7 [1-11] versus 87 [60-130] MME; P < 0.001) per postoperative day over a similar length of stay (8 [7-10] versus 6 [6-10] days; P = 0.14). Fewer outpatient MMEs were prescribed within the first 60 days after LT in the opioid avoidance group versus the historical cohort: 125 (25-150) versus 270 (0-463) MME (P = 0.05). This proof-of-concept study outlines the potential to profoundly reduce opioid utilization in the LT population using a comprehensive multidisciplinary approach.
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http://dx.doi.org/10.1002/lt.25847DOI Listing
October 2020

Clinical Impact of Antecedent Bariatric Surgery on Liver Transplant Outcomes: A Retrospective Matched Case-control Study.

Transplantation 2021 06;105(6):1280-1284

Division of Transplantation, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN.

Background: Bariatric surgery (BS) may be associated with significant malabsorption and nutritional deficiencies.

Methods: Between March 1987 and January 2017, we performed 922 liver transplants (LT) at our institution; 33 had antecedent BS. We matched the BS cohort to LT recipients without BS (1:3 matching) based on exact matching for gender and cancer and inverse variance matching for age, LT body mass index, MELD score, and transplant date.

Results: We analyzed outcomes in 132 LT recipients (33 BS; 99 non-BS). The BS cohort comprised 26 (79%) women with a mean age of 52.4 years. The BS procedures included 20 Roux-en-Y gastric bypass (61%), 6 jejunoileal bypass (18%), 3 gastric band (9%), 2 sleeve gastrectomy (6%), and 1 duodenal switch (3%). The primary indications for LT listing were alcoholic cirrhosis (9; 27%), nonalcoholic steatohepatitis (7; 21%), hepatitis C (8; 24%), and hepatocellular carcinoma (3; 9%). At LT, body mass index for the BS cohort was 29.6, and MELD was 24. Compared with matched controls, BS recipients did not have longer LT length of hospital stay (17.8 versus 15.7 d, P = 0.71), longer intensive care unit length of stay (5.3 versus 4.1 d, P = 0.16), or higher 30-day complication rate (76% versus 85%, P = 0.43). Overall patient survival was similar (1- and 3-y survival was 90.1% and 75.9% for BS; 90.9% and 76.4% for non-BS, P = 0.34).

Conclusions: A history of BS does not portend a deleterious effect on LT outcomes.
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http://dx.doi.org/10.1097/TP.0000000000003378DOI Listing
June 2021

Incidental COVID-19 in a heart-kidney transplant recipient with malnutrition and recurrent infections: Implications for the SARS-CoV-2 immune response.

Transpl Infect Dis 2020 Dec 1;22(6):e13367. Epub 2020 Jul 1.

Hartford Hospital Transplant & Comprehensive Liver Center, Hartford, Connecticut, USA.

The clinical course and outcomes of immunocompromised patients, such as transplant recipients, with COVID-19 remain unclear. It has been postulated that a substantial portion of the disease burden seems to be mediated by the host immune activation to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present a simultaneous heart-kidney transplant (SHKT) recipient who was hospitalized for the management of respiratory failure from volume overload complicated by failure to thrive, multiple opportunistic infections, and open non-healing wounds in the setting of worsening renal dysfunction weeks prior to the first case of SARS-CoV-2 being detected in the state of Connecticut. After his third endotracheal intubation, routine nucleic acid testing (NAT) for SARS-CoV-2, in anticipation of a planned tracheostomy, was positive. His hemodynamics, respiratory status, and ventilator requirements remained stable without any worsening for 4 weeks until he had a negative NAT test. It is possible that the immunocompromised status of our patient may have prevented significant immune activation leading up to clinically significant cytokine storm that could have resulted in acute respiratory distress syndrome and multisystem organ failure.
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http://dx.doi.org/10.1111/tid.13367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323106PMC
December 2020

Successful management of noncirrhotic hyperammonemia syndrome after kidney transplantation from putative Ureaplasma infection.

Transpl Infect Dis 2020 Oct 13;22(5):e13332. Epub 2020 Jun 13.

Hartford Hospital Transplant Program, Hartford, CT, USA.

Noncirrhotic hyperammonemia (NCH) is a rare but often fatal complication of solid organ transplantation. We present a case wherein an infectious cause of NCH was suspected following kidney transplantation (KT) and the patient was promptly started on empirical antibiotic treatment which proved to be lifesaving. A 56-year-old Chinese woman with a past medical history of end-stage renal disease secondary to ischemic nephropathy and cerebrovascular accident received a kidney from a 52-year-old brain-dead donor with a Kidney Donor Profile Index score of 70%. She experienced immediate graft function and was discharged on post-operative day (POD) 4. On POD 10, she presented with a fever, acute onset of confusion, and abdominal pain. Her mental status deteriorated and required emergent intubation. Empiric broad-spectrum antibiotics were initiated. On hospital day 3, a serum ammonia was 889 μmol/L (normal <53 μmol/L). A urine sample was sent for Ureaplasma polymerase chain reaction (PCR) testing, and moxifloxacin and doxycycline were empirically started. Her ammonia rapidly normalized, and her mental status improved 48 hours after antibiotic initiation. She was extubated 5 days into treatment and was discharged after an 11-day hospitalization. Following discharge, her urine test resulted positive for Ureaplasma parvum or Ureaplasma urealyticum DNA detection with the 16S rRNA gene amplification probe. Mental status changes and hyperammonemia in the first 30 days post-KT should raise suspicion for NCH, and prompt empiric treatment with antimicrobials covering Ureaplasma and Mycoplasma should be considered.
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http://dx.doi.org/10.1111/tid.13332DOI Listing
October 2020

Deceased donor kidney transplant complicated by spontaneous rupture of native kidney in a HIV patient.

CEN Case Rep 2020 05 27;9(2):182-185. Epub 2020 Jan 27.

Hartford Hospital Transplant and Comprehensive Liver Center, 85 Seymour Street, Suite 320, Hartford, CT, 06106, USA.

Spontaneous native kidney rupture (SNKR) is a rare occurrence, commonly associated with underlying renal tumors or acquired renal cystic disease in both the kidney transplant (KT) and non-KT populations. Herein, we present a 65-year-old African American man who experienced a non-malignant SNKR 6 days after a deceased donor KT and underwent emergent native nephrectomy. The patient's hospital course was complicated by thrombocytopenia and refractory hypertension. He experienced delayed graft function and was maintained on hemodialysis until post-operative day 30. This case demonstrates an unusual presentation of SNKR in the immediate post-KT setting and illustrates the clinical decision-making algorithm.
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http://dx.doi.org/10.1007/s13730-020-00453-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148391PMC
May 2020

Long-term outcomes of pediatric kidney transplant recipients with a pretransplant malignancy.

Pediatr Transplant 2019 11 13;23(7):e13557. Epub 2019 Aug 13.

Department of Surgery, Division of Transplantation, University of Minnesota, Minneapolis, Minnesota.

A childhood malignancy can rarely progress to ESRD requiring a KT. To date, few reports describe long-term outcomes of pediatric KT recipients with a pretransplant malignancy. Between 1963 and 2015, 884 pediatric (age: 0-17 years old) recipients received 1055 KTs at our institution. KT outcomes were analyzed in children with a pretransplant malignancy. We identified 14 patients who had a pretransplant malignancy prior to KT; the majority were <10 years old at the time of KT. Ten (71%) patients received their grafts from living donors, the majority of which were related to the recipient. Wilms' tumor was the dominant type of pretransplant malignancy, seen in 50% of patients. The other pretransplant malignancy types were EBV-positive lymphoproliferative disorders, non-EBV-positive lymphoma, leukemia, neuroblastoma, soft-tissue sarcoma, and ovarian cancer. Ten of the 14 patients received chemotherapy as part of their pretransplant malignancy treatment. Graft survival at 1, 3, and 5 years was 93%, 83%, and 72%, respectively. Patient survival at 1, 5, and 10 years was 100%, 91%, and 83%, respectively. Six (40%) patients suffered AR following KT; half of them had their first episode of AR within 1 month of KT. Our single-center experience demonstrates that pediatric KT recipients with a previously treated pretransplant malignancy did not exhibit worse outcomes than other pediatric KT patients.
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http://dx.doi.org/10.1111/petr.13557DOI Listing
November 2019

Aggressive Epstein-Barr virus-negative B-cell post-transplant lymphoproliferative disorder in a hepatitis C-negative liver transplant recipient who received a hepatitis C-positive graft: Implications for D+/R- hepatitis C virus seroconversion.

Transpl Infect Dis 2019 Oct 22;21(5):e13144. Epub 2019 Jul 22.

Hartford Hospital Transplant & Comprehensive Liver Center, Hartford, Connecticut.

Post-transplant lymphoproliferative disorder (PTLD) is an uncommon, but well-described complication after liver transplantation. Most recently, Hepatitis C virus (HCV) has been implicated in the development of PTLD. A HCV-negative 62-year-old man with autoimmune hepatitis received a HCV nucleic acid amplification test-positive liver graft from a 73-year-old brain-dead donor (D+/R-). After his recovery from the operation, the patient was treated for HCV and achieved an undetectable viral load. He was readmitted 6 months after transplant with a spontaneous perisplenic hematoma, weight loss, failure to thrive, low-grade fevers, and abnormal liver function tests. He had a rapid clinical deterioration and expired shortly after admission. His liver biopsy demonstrated EBV-negative monomorphic B-cell PTLD. Our case is the first to report an aggressive early-onset EBV-negative monomorphic B-cell PTLD in a HCV D+/R- liver transplant. This case illustrates the paucity of knowledge on HCV seroconversion and its involvement in EBV-negative monomorphic B-cell PTLD development.
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http://dx.doi.org/10.1111/tid.13144DOI Listing
October 2019

Maximizing Deceased-Donor Allograft Utilization: Management of a Celiac Artery Aneurysm in a Deceased-Donor Liver.

Exp Clin Transplant 2021 Oct 25;19(10):1103-1105. Epub 2019 Jun 25.

From the Division of Transplantation, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA.

As the scarcity of transplantable organs continues to rise, compounded with an aging donor population, transplant surgeons are increasingly confronted with organ offers from less than ideal donors. The presence of a celiomesenteric aneurysm involving the vascular supply of a donor allograft may predispose to vascular complications in the transplanted liver. We present a 61-year-old brain-dead donor who was discovered to have a celiac artery aneurysm during organ recovery. After gross atherosclerotic or mycotic involvement was ruled out and after careful consideration of the vascular reconstructive options, the donor common hepatic artery was divided distal to the aneurysmal dilatation and anastomosed to the recipient bifurcation of the left and right hepatic artery in an end-to-end beveled anastomosis. The postoperative course was unre-markable, with normal blood flow through the anastomosis and no significant com-plications. The recipient is doing well 6 months after transplant. The presence of a celiomesenteric aneurysm should not discourage the use of an otherwise adequate liver graft. Careful vascular reconstruction is encouraged to increase the rate of marginal graft utilization and minimize vascular complications. Liberal postoperative imaging can enable early detection of vascular com-plication and prompt intervention. Through this case, we demons-trate the remarkable potential of less-than-ideal grafts with acceptable posttransplant outcomes.
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http://dx.doi.org/10.6002/ect.2019.0023DOI Listing
October 2021

Delivery of transplant care among Hmong kidney transplant recipients: Outcomes from a single institution.

Clin Transplant 2019 05 6;33(5):e13539. Epub 2019 Apr 6.

Division of Transplantation, Department of Surgery, Minneapolis, Minnesota.

Kidney transplantation entails well-coordinated complex care delivery. Patient-provider cultural and linguistic discordance can lead to healthcare disparities. We analyzed kidney transplantation outcomes among our institution's Hmong recipients using a retrospective cohort study. From 1995 to 2015, 2164 adult (age ≥18) recipients underwent kidney transplantation at our institution; 78 self-identified as Hmong. Survival rates were analyzed and compared to Caucasian recipients (n = 2086). Fifty (64.1%) Hmong recipients consistently requested interpreters. Mean follow-up was 9.8 years for both groups. Hmong recipients (N = 78) were on average younger at transplant (45.7 vs 49.7 years; P = 0.02), more likely to be female (56% vs 38%; P = 0.001), and had higher gravidity (5.0 vs 1.9 births; P < 0.001). There were 13 (16.7%) Hmong living donor recipients, who were younger (32.8 vs 42.9 years; P = 0.006) at transplant compared to Caucasians (1429, 68.5%). Hmong 1- and 5-year patient survival was 100%; Caucasians, 97.1% and 88% (P < 0.001). Hmong 1- and 5-year graft survival was 98.7% and 84.9%; Caucasians 94.8% and 80.9% (P = 0.013). One- and 5-year rejection-free survival showed no difference (88.9% vs 82.4%; 86.7% vs 83.4%, P = 0.996). Despite cultural and linguistic differences between Hmong recipients and providers, we found no evidence of inferiority in KT outcomes in the Hmong population.
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http://dx.doi.org/10.1111/ctr.13539DOI Listing
May 2019

Retransplant Outcomes Compared With First Kidney Transplants: Important Observations Not Reported in the Scientific Registry of Transplant Recipients Annual Report.

Exp Clin Transplant 2020 02 22;18(1):48-52. Epub 2019 Feb 22.

From the Department of Surgery, Division of Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.

Objectives: Twice per year, the Scientific Registry of Transplant Recipients provides risk-adjusted center-specific reports of 1- and 3-year outcomes. In addition, the Registry reports 10-year aggregate survival outcomes for kidney transplant recipients. However, in this annual report, no distinction is made between outcomes of patients with a first transplant versus those with retransplants.

Materials And Methods: We analyzed data from the Scientific Registry of Transplant Recipients between 1992 and 2015 to determine outcomes after a 1st, 2nd, or ≥ 3rd kidney transplant. Recipients were stratified by donor source (living vs deceased) and transplant number, and rates of graft failure, death-censored graft failure, and death with functioning graft were determined.

Results: From 1992 to 2015, rates of graft failure and death-censored graft failure at 6 months, 1 year, 3 years, 5 years, and 10 years decreased; however, long-term rates of death with functioning graft were unchanged. Outcomes for 1st and 2nd kidney transplant were better than outcomes for ≥ 3rd transplant.

Conclusions: It would be extremely valuable if the Scientific Registry of Transplant Recipients could present stratified analyses that would account for a host of factors, including organ sequence, which tend to vary by center. The presentation of risk-adjusted outcomes in the annual Registry report could include a more comprehensive assessment of program performance. Such information would be extremely useful for transplant centers, patients, and their support networks, organ procurement organizations, and other transplant stakeholders.
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http://dx.doi.org/10.6002/ect.2018.0244DOI Listing
February 2020

Influence of the procurement surgeon on transplanted abdominal organ outcomes: An SRTR analysis to evaluate regional organ procurement collaboration.

Am J Transplant 2019 08 18;19(8):2219-2231. Epub 2019 Mar 18.

Division of Transplantation, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.

Single-center studies have demonstrated regional organ procurement collaboration to reduce travel redundancy and improve procurement efficiency. We studied deceased donor kidney, liver, and pancreas transplants performed in the United States between 2002 and 2014 using the Scientific Registry of Transplant Recipients (SRTR). We compared graft failure (GF), death-censored graft failure (DCGF), and patient death (PD) between organs procured by surgeons from the recipient's center (transplant procurement team [TPT]) versus surgeons from a different center (NTPT). Primary nonfunction (PNF) was assessed for liver and kidney and delayed graft function (DGF) for kidney using mixed-effects logistic modeling. There were 64 906 liver (61.6% TPT), 118 152 kidney (26.1% TPT), 10 832 simultaneous pancreas kidney (SPK; 56.6% TPT), and 4378 solitary pancreas (SP; 34.0% TPT) transplants. When compared to NTPT, DCGF for organs procured by TPT was significantly less for liver (adjusted HR: 0.93; 95% CI: 0.88-0.98) and marginally significant for kidney (0.97; 0.93-1.00) and SPK (0.90; 0.82-1.00), and not significant for SP (0.98; 0.86 -1.11). DGF for TPT kidney was significantly lower (adjusted OR 0.91; 0.87-0.95). Albeit modest, our findings demonstrate a difference between locally procured organs and those procured by the implanting team. Elucidating the etiology of these differences will enhance regional organ procurement collaboration.
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http://dx.doi.org/10.1111/ajt.15301DOI Listing
August 2019

Clinical utility of postoperative phosphate recovery profiles to predict liver insufficiency after living donor hepatectomy.

Am J Surg 2019 08 11;218(2):374-379. Epub 2019 Jan 11.

Division of Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.

Background: Living donor hepatectomy (LDH) is associated with significant postoperative hypophosphatemia.

Methods: From January 1997 through July 2017, we performed 176 LDH and compared donors who developed liver insufficiency (LI) to those that did not within 30 days of LDH. Using smoothing splines, we constructed a mixed-effects model and assessed receiver operating characteristic curves.

Results: Of the 176 donors, 161 were included in our study and 10 (6.2%) developed LI. The cohorts differed in minimum observed phosphate levels (1.77 mg/dL, LI cohort; 2.01 mg/dL No LI cohort) at a median nadir of 1.6 days (38 h) postoperatively (p = 0.003). In the ROC analysis, intraoperative time and postoperative phosphate levels best predicted LI (sensitivity, 90%; specificity, 55.6%).

Conclusion: Mean postoperative phosphate profiles differ significantly between those patients who develop LI and those who do not in the first 38 h after LDH.
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http://dx.doi.org/10.1016/j.amjsurg.2019.01.006DOI Listing
August 2019

Transjugular Removal of a Retained Intraportal Procurement Cannula in a Liver Transplant Recipient.

J Vasc Interv Radiol 2018 12;29(12):1778-1780

Division of Transplantation, Department of Surgery, University of Minnesota Medical School, Mayo Mail Code 195, 420 Delaware Street SE, Minneapolis, MN 55455.

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http://dx.doi.org/10.1016/j.jvir.2018.07.016DOI Listing
December 2018

Incidence and magnitude of post-transplant cardiovascular disease after pediatric kidney transplantation: Risk factor analysis of 1058 pediatric kidney transplants at the university of Minnesota.

Pediatr Transplant 2018 11 27;22(7):e13283. Epub 2018 Aug 27.

Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.

Background: KT recipients have increased the risk of CVD. The incidence of post-transplant CVEs among pediatric recipients has not been well-characterized.

Patients And Methods: Between 1963 and 2015, 884 pediatric (age: 0-17 years old) recipients received 1058 KTs at our institution. The cumulative incidence of CVEs was analyzed. Statistical models were used to estimate risk factors for developing post-transplant CVEs.

Results: Overall median patient survival was 33 years (IQR: 18.7-47). A total of 362 CVEs occurred in 161 (18.3%) patients at a median age of 20.5 years. Arrhythmias (18%) were most common. Cumulative risk of post-transplant CVEs was 9% at 10 years, 17% at 20 years, 25% at 30 years, and 36% at 40 years. Development of post-transplant CVEs was associated with increased mortality (HR 2.25 [95% CI 1.61-3.14]); of those who developed a CVE and died, 22/51 (43.1%) died of CVD. Multivariable risk factors for post-transplant CVEs included a history of pretransplant CVD (aHR 1.92 [1.18-3.13] and graft failure (4.57 [3.13-6.67]).

Discussion: A pretransplant history of CVD and a failed graft are significant risk factors for the development of post-transplant CVE. CVD increases the risk of post-transplant death or graft loss.
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http://dx.doi.org/10.1111/petr.13283DOI Listing
November 2018

Implications of excess weight on kidney donation: Long-term consequences of donor nephrectomy in obese donors.

Surgery 2018 Nov 24;164(5):1071-1076. Epub 2018 Aug 24.

Division of Transplantation, Department of Surgery, University of Minnesota, Minneapolis.

Background: An elevated body mass index (>30 kg/m) has been a relative contraindication for living kidney donation; however, such donors have become more common. Given the association between obesity and development of diabetes, hypertension, and end-stage renal disease, there is concern about the long-term health of obese donors.

Methods: Donor and recipient demographics, intraoperative parameters, complications, and short- and long-term outcomes were compared between contemporaneous donors-obese donors (body mass index ≥30 kg/m) versus nonobese donors (body mass index <30 kg/m).

Results: Between the years 1975 and 2014, we performed 3,752 donor nephrectomies; 656 (17.5%) were obese donors. On univariate analysis, obese donors were more likely to be older (P < .01) and African American (P < .01) and were less likely to be a smoker at the time of donation (P = .01). Estimated glomerular filtration rate at donation was higher in obese donors (115 ± 36 mL/min/1.73m) versus nonobese donors (97 ± 22 mL/min/1.73m; P < .001). There was no difference between groups in intraoperative and postoperative complications; but intraoperative time was longer for obese donors (adjusted P < .001). Adjusted postoperative length of stay (LOS) was longer (adjusted P = .01), but after adjustment for donation year, incision type, age, sex, and race, there were no differences in short-term (<30 days) and long-term (>30 days) readmissions. Estimated glomerular filtration rate and rates of end-stage renal disease were not significantly different between donor groups >20 years after donation (P = .71). However, long-term development of diabetes mellitus (adjusted hazard ratio (HR) 3.14; P < .001) and hypertension (adjusted hazard ratio (HR) 1.75; P < .001) was greater among obese donors and both occurred earlier (diabetes mellitus: 12 vs 18 years postnephrectomy; hypertension: 11 vs 15 years).

Conclusion: Obese donors develop diabetes mellitus and hypertension more frequently and earlier than nonobese donors after donation, raising concerns about increased rates of end-stage renal disease.
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http://dx.doi.org/10.1016/j.surg.2018.07.015DOI Listing
November 2018

Age alone is not a contraindication to kidney donation: Outcomes of donor nephrectomy in the elderly.

Clin Transplant 2018 08 20;32(8):e13287. Epub 2018 Jun 20.

Division of Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.

With increasing organ demand, living kidney donation from older donors (>60-years-old) has become more common. Between 1975 and 2014, 3752 donor nephrectomies (DN) were performed at University of Minnesota; 167 (4.5%) were >60-years-old Short- and long-term outcomes were compared between contemporaneous >60-years-old and <60-years-old donors. On univariate analysis, >60-years-old were more likely to have had prior abdominal surgery and hypertension; and less likely to smoke. Baseline estimated glomerular filtration rate (eGFR) was lower in >60-years-old (80 ± 16 vs 101 ± 26 mL/min/1.73 m ; P < .001). Intraoperative and postoperative complications were similar, except a higher prevalence of <30 day ileus (3% vs 7%; P = .021) and longer postoperative length of stay (LOS) (4.2 vs 4.6 days; P = .005). On multivariate analysis, <30 day ileus and LOS continued to be significantly greater for >60-years-old After >20 years post-DN, systolic blood pressure was significantly higher among >60-years-old (142 vs 125 mm Hg; P < .001) and HTN was diagnosed earlier (9 vs 14 years). After donation, eGFR was significantly lower for >60-years-old but slope of eGFR and rates of end-stage renal disease (ESRD) were not significantly different >20 years post-DN. Thus, kidney donation among carefully selected >60-years-old poses minimal perioperative risks and no added risk of long-term ESRD.
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http://dx.doi.org/10.1111/ctr.13287DOI Listing
August 2018

Incidental Neuroendocrine Tumor Discovered After Total Pancreatectomy Intended for Islet Autotransplantation: Important Considerations for Surgical Decision-Making.

Pancreas 2018 07;47(6):778-782

Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Medical School, Minneapolis, MN.

Total pancreatectomy (TP) is a treatment option for patients experiencing chronic pancreatitis (CP) refractory to medical management. Patients who are candidates for TP benefit from islet autotransplantation (IAT), which preserves available β-cell mass and thereby reduces the risk of brittle diabetes. Malignancy is an absolute contraindication for IAT to prevent the transplantation of occult malignant cells. We present the case of a patient with CP who was approved to undergo TP with IAT (TPIAT) but was intraoperatively discovered to have a pancreatic neuroendocrine tumor. The case illustrates a number of important surgical decision-making considerations for patients undergoing TPIAT and should help guide surgeons should they be presented with this clinical scenario. We stress the importance of vigilance for possible malignancy and to consider an intraoperative biopsy to further investigate unexpected findings that might represent an occult pancreatic malignancy in patients with CP undergoing TPIAT.
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http://dx.doi.org/10.1097/MPA.0000000000001069DOI Listing
July 2018

The Relationships Between Cold Ischemia Time, Kidney Transplant Length of Stay, and Transplant-related Costs.

Transplantation 2019 02;103(2):401-411

Division of Transplantation, Department of Surgery, School of Public Health.

Background: Recent changes in policies guiding allocation of transplant kidneys are predicted to increase sharing between distant geographic regions. The potential exists for an increase in cold ischemia time (CIT) with resulting increases in delayed graft function (DGF) and transplant-related costs (TRC). We sought to explore the impact of CIT on metrics that may influence TRC.

Methods: Between 2006 and 2014, 81 945 adult solitary deceased donor kidney transplants were performed in the United States; 477 (0.6%) at our institution. Regression models were constructed to describe the relationship between CIT on DGF and length of stay (LOS). Using hospital accounting data, we created regression models to evaluate the effect of DGF on LOS and TRC.

Results: In multivariable models, longer CIT was associated with an increased rate of DGF (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.38-1.44) and increased LOS (OR, 1.04; 95% CI, 1.02-1.05). Recipients at our institution who developed DGF had longer LOS (OR, 1.71; 95% CI, 1.50-1.95), suggesting that the effect is partially mediated by DGF. After adjusting for LOS, neither CIT nor DGF were independently associated with increased TRC. However, an increased LOS resulted in an increase in TRC by US $3422 (95% CI, US $3180 to US $3664) per additional day, indicating that the effect of CIT on TRC is partially mediated through LOS.

Conclusions: The prolongation of CIT is associated with an increase in DGF rates and LOS, resulting in increased TRC. This study raises the need to balance increased access of traditionally underserved populations to kidney transplant with the inadvertent increase in TRC.
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http://dx.doi.org/10.1097/TP.0000000000002309DOI Listing
February 2019
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