Publications by authors named "Akin Tekin"

51 Publications

Intestinal transplantation.

Curr Opin Organ Transplant 2021 Apr;26(2):229-233

Departmetn of Surgery, Liver and Gastrointestinal Transplantation, Miami Transplant Institute, University of Miami/Jackson Memorial Hospital, Miami, Florida, USA.

Purpose Of Review: Intestinal transplantation has evolved to be a viable treatment option for patients with intestinal failure. This review shows the most current tendencies and practices of intestinal transplant centers and an overall comparison to intestinal rehabilitation.

Recent Findings: This review outlines that timing for referral and advances in preoperative and postoperative care of intestinal and multivisceral transplant candidates are crucial to achieve results comparable to intestinal rehabilitation.

Summary: Current practices have shown that intestinal transplantation continues to improve overall results and could be considered in patients with permanent home parenteral nutrition. Timing for referral and preoperative and postoperative management are crucial to optimize long-term results.
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http://dx.doi.org/10.1097/MOT.0000000000000865DOI Listing
April 2021

A Less Restrictive Policy for Liver Transplantation in Coronavirus Disease 2019 Positive Patients, Based Upon Cycle Threshold Values.

Transplant Proc 2021 Jan 20. Epub 2021 Jan 20.

Department of Anesthesia, University of Miami/Jackson Memorial Hospital, Miami, Florida.

Coronavirus disease 2019 drastically impacted solid organ transplantation. Lacking scientific evidence, a very stringent but safer policy was imposed on liver transplantation (LT) early in the pandemic. Restrictive transplant guidelines must be reevaluated and adjusted as data become available. Before LT, the prevailing policy requires a negative severe acute respiratory syndrome coronavirus 2 real-time polymerase chain reaction (RT-PCR) of donors and recipients. Unfortunately, prolonged viral RNA shedding frequently hinders transplantation. Recent data reveal that positive test results for viral genome are frequently due to noninfectious and prolonged convalescent shedding of viral genome. Moreover, studies demonstrated that the cycle threshold of quantitative RT-PCR could be leveraged to inform clinical transplant decision-making. We present an evidence-adjusted and significantly less restrictive policy for LT, where risk tolerance is tiered to recipient acuity. In addition, we delineate the pretransplant clinical decision-making, intra- and postoperative management, and early outcome of 2 recipients of a liver graft performed while their RT-PCR of airway swabs remained positive. Convalescent positive RT-PCR results are common in the transplant arena, and the proposed policy permits reasonably safe LT in many circumstances.
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http://dx.doi.org/10.1016/j.transproceed.2021.01.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816591PMC
January 2021

Liver transplantation as a novel strategy for resolution of congenital afibrinogenemia in a pediatric patient.

J Thromb Haemost 2020 12 6;18(12):3232-3235. Epub 2020 Oct 6.

Nicklaus Children's Hospital, Miami, FL, USA.

Fibrinogen replacement therapy is a treatment mainstay for patients with afibrinogenemia and significant bleeding. A male infant with congenital afibrinogenemia and several spontaneous hemarthroses commenced cryoprecipitate prophylaxis but developed severe urticarial reactions. He transitioned to a human fibrinogen concentrate (HFC) (RiaSTAP , CSL Behring; 70 mg/kg biweekly) but continued experiencing hemarthroses (estimated annualized bleeding rate [ABR]: 5-6) and severe anaphylactic reactions, despite pre- and postinfusion medications. Following switching to a new HFC (Fibryga , Octapharma; 50 mg/kg biweekly), ABR was 0-1 with no further infusion reactions. Aged 9 years, because of limited quality of life, development of obesity and fatty liver disease, he underwent orthotopic liver transplant (OLT) under HFC coverage. Pharmacokinetic analysis guided presurgical fibrinogen levels > 150 mg/dL. No intraoperative HFC infusions were required. Coagulation profile and fibrinogen levels remained within normal limits during and posttransplant. To our knowledge, this is the first pediatric report of afibrinogenemia successfully treated with OLT.
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http://dx.doi.org/10.1111/jth.15090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756576PMC
December 2020

Multivisceral transplant as an option to transplant cirrhotic patients with severe portal vein thrombosis.

Int J Surg 2020 Oct 30;82S:115-121. Epub 2020 Jul 30.

University of Indiana, USA. Electronic address:

Non-tumoral portal vein thrombosis (PVT) is a critical complication in the patient with advanced cirrhosis awaiting liver transplantation (LT). With the evolution of liver transplant (LT) technique, PVT has morphed from an absolute contraindication to a relative contraindication, depending on the grade of the thrombus. The Yerdel classification is one system of grading PVT severity. Patients with Yerdel class 1-3 PVT can undergo LT at centers with experience in complex portal vein (PV) dissection, thrombectomy, and reconstruction. Class 4 PVT, however, is even more complex and may require heroic techniques such as cavoportal hemitransposition, PV arterialization or multivisceral transplant (MVT). Some centers use a MVT back-up approach for patients with Yerdel class 4 PVT. In these patients, all organs with PV outflow are procured simultaneously as a cluster graft from a deceased donor (liver, pancreas, intestine±stomach). If physiologic PV inflow is established intraoperatively, the recipient undergoes LT. Otherwise the MVT graft is transplanted. MVT establishes physiologic PV flow, but transplantation of the intestine confers significant lifelong risks including rejection, graft-versus host disease and post-transplant lymphoma. Yerdel class 1-4 PVT patients undergoing successful LT have 5-year survival similar to non-PVT patients, while patients requiring full MVT experience somewhat higher mortality because of the complexity of the surgery and medical management.
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http://dx.doi.org/10.1016/j.ijsu.2020.07.010DOI Listing
October 2020

En-Bloc Simultaneous Heart-Liver Transplantation in Adult Patients.

Ann Surg 2020 Jan 14. Epub 2020 Jan 14.

Department of Surgery, Division of Liver and Gastrointestinal Transplantation, Miami Transplant Institute, Miami, FL.

Introduction: Complexity of combined heart-liver transplantation has resulted in low adoption rates. We report a case series of adult patients receiving en-bloc heart-liver transplantation (HLTx), describe technical aspects, and discuss benefits of the technique.

Methods: Retrospective review of patients receiving en-bloc HLTx over 18 months, with clinical follow up to 1 year. Primary outcomes included postoperative mortality and major complications. Secondary outcomes included 1-year survival, cardiac or hepatic allograft rejection, and infection.

Results: Five patients received en-bloc HLTx. Mean recipient age was 43 years (26-63), and 3 patients were male. Total operative time was 430 minutes (393-480), cold and warm ischemic times of 85 (32-136) and 37.5 (31-47) minutes. Hospital survival was 80%. One patient died on postoperative day 55 due to fungal sepsis. Major postoperative complications included prolonged mechanical ventilation in 2 of 5 patients (40%), and renal insufficiency requiring hemodialysis in 2 of 5 patients (40%). Among patients discharged from hospital 1-year survival was 100%, with no evidence of rejection or infectious complications.

Conclusion: En-bloc HLTx technique is a safe and effective strategy, decreasing operative times, and allograft ischemic times, whereas offering protection of implanted allografts during early stages of reperfusion while patient is hemodynamically supported on cardiopulmonary bypass.
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http://dx.doi.org/10.1097/SLA.0000000000003721DOI Listing
January 2020

Association of Alemtuzumab Induction With a Significantly Lower Incidence of GVHD Following Intestinal Transplantation: Results of 445 Consecutive Cases From a Single Center.

Transplantation 2020 10;104(10):2179-2188

Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL.

Background: In intestinal transplantation, graft versus host disease (GVHD), while relatively rare, remains a major cause of morbidity and mortality posttransplant. Because of its rarity of occurrence, no multivariable analysis of risk factors for GVHD development has previously been reported.

Methods: We used Cox stepwise regression to determine the significant multivariable predictors of the hazard rate of developing biopsy-proven GVHD during the first 60 months posttransplant among 445 consecutive intestinal transplant cases at our center since 1994.

Results: GVHD was observed in 8.8% (39/445); median time-to-GVHD development (range) was 1.5 months (0.5-17.3 mo) posttransplant. Sites of GVHD included skin (N = 21), skin/gastrointestinal tract (N = 6), gastrointestinal tract/rectum (N = 4), skin/liver (N = 4), skin/lung (N = 2), skin/rectum (N = 1), and skin/bone marrow (N = 1). Three factors were selected into the Cox model offering significant protection from GVHD development (listed in order of selection): isolated intestine or liver-intestine (LI) (versus modified multivisceral [MV] or MV) allograft (P = 0.00003), alemtuzumab (versus no induction, anti-CD25, rabbit antithymocyte globulin, or rabbit antithymocyte globulin/rituximab) induction (P = 0.004), and liver inclusion (LI or MV) (P = 0.009). These results remained unchanged even after accounting for the propensity to receive alemtuzumab induction. Observed GVHD incidence was 2.4% (3/125), 0.0% (0/38), 17.9% (7/39), and 11.9% (29/243) for isolated intestine, LI, modified MV, and MV allografts, and 2.7% (3/113) versus 10.8% (36/332) for those receiving versus not receiving alemtuzumab induction, respectively.

Conclusions: These results may help advance the current state of knowledge about risk factors for GVHD development following intestinal transplantation.
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http://dx.doi.org/10.1097/TP.0000000000003111DOI Listing
October 2020

Association of More Intensive Induction With Less Acute Rejection Following Intestinal Transplantation: Results of 445 Consecutive Cases From a Single Center.

Transplantation 2020 10;104(10):2166-2178

Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL.

Background: In intestinal transplantation, acute cellular rejection (ACR) remains a significant challenge to achieving long-term graft survival. It is still not clear which are the most important prognostic factors.

Methods: We performed a Cox multivariable analysis of the hazard rates of developing any ACR, severe ACR, and cause-specific graft loss during the first 60 months posttransplant among 445 consecutive intestinal transplant recipients at our institution since 1994. Of particular interest was to determine the prognostic influence of induction type: rabbit antithymocyte globulin (rATG; 2 mg/kg × 5)/rituximab (150 mg/m × 1; begun in 2013), alemtuzumab (2001-2011), and less intensive forms.

Results: First ACR and severe ACR occurred in 61.3% (273/445) and 22.2% (99/445) of cases. The following 3 multivariable predictors were associated with significantly lower hazard rates of developing ACR and severe ACR: transplant type modified multivisceral or full multivisceral (P = 0.0009 and P < 0.000001), rATG/rituximab induction (P < 0.000001 and P < 0.01), and alemtuzumab induction (P = 0.004 and P = 0.07). For both ACR and severe ACR, the protective effects of rATG/rituximab and alemtuzumab were highly significant (P ≤ 0.000005 for ACR; P ≤ 0.01 for severe ACR) but only during the first 24 days posttransplant (when the ACR hazard rate was at its peak). The prognostic effects of rATG/rituximab and alemtuzumab on ACR/severe ACR disappeared beyond 24 days posttransplant (ie, nonproportional hazards). While significant protective effects of both rATG/rituximab and alemtuzumab existed during the first 6 months posttransplant for the hazard rate of graft loss-due-to-rejection (P = 0.01 and P = 0.003), rATG/rituximab was additionally associated with a consistently lower hazard rate of graft loss-due-to-infection (P = 0.003). All significant effects remained after controlling for the propensity-to-be-transplanted since 2013.

Conclusions: More intensive induction was associated with a significant lowering of ACR risk, particularly during the early posttransplant period.
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http://dx.doi.org/10.1097/TP.0000000000003074DOI Listing
October 2020

Clostridium difficile infection mimics intestinal acute cellular rejection in pediatric multivisceral transplant-A case series.

Pediatr Transplant 2020 02 9;24(1):e13621. Epub 2019 Dec 9.

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Miami, Miami, FL, USA.

Clostridium difficile infection (CDI) is the most common health care-associated infection in the United States. Thirty-nine percent of intestinal transplant recipients may develop CDI. Induction of rejection has been reported as a rare event. To our knowledge, this will be the second report of an association between CDI and rejection in the literature. We describe our experience with four pediatric MVT recipients, three of whom on treatment of their CDI alone had resolution of biopsy findings of intestinal ACR. Our patients were males aged 2-5 years old who had their first CDI post-MVT occurring from 2 months to 15 months post-transplant. All first episodes of CDI were treated with a 10-14 day course of metronidazole with one additionally receiving vancomycin. All four recipients had recurrent CDI, and two recipients had septic shock as a manifestation of their CDI. Three recipients had biopsies showing mild rejection during episodes of CDI, and treatment of the CDI resulted in resolution of biopsy findings of rejection. Our case series suggests CDI may mimic ACR on intestinal biopsy. Treatment of rejection during active CDI carries the risk of over-suppression and worsening of CDI. Our experience has taught us that surveillance endoscopy for rejection may be deceiving during an active CDI, and if mild acute rejection is noted during active CDI, treatment of rejection can be safely delayed and potentially avoided.
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http://dx.doi.org/10.1111/petr.13621DOI Listing
February 2020

Comprehensive Frailty Severity Index for End-Stage Liver Disease Predicts Early Outcomes After Liver Transplantation.

JPEN J Parenter Enteral Nutr 2020 08 8;44(6):1079-1088. Epub 2019 Nov 8.

Department of Anesthesia, University of Miami/Jackson Memorial Hospital, Miami, Florida, USA.

Background: Frailty is rampant in candidates of liver transplantation (LT); however, its impact on posttransplant survival is inconclusive. Most studies have used a single measure of frailty; however, a comprehensive frailty severity index (FSI) has not been developed. The objectives of this study were to (1) evaluate frailty utilizing several metrics, (2) develop an FSI for end-stage liver disease (ESLD), and (3) determine its predictive abilities for outcomes after LT.

Methods: Frailty metrics included (1) modified nutrition assessment of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition that includes height-adjusted third lumbar vertebra psoas mass index, (2) physical performance assessment combining Karnofsky Performance Status and pressure injury scale, and (3) Controlling Nutritional Status as a measure of severity of liver disease and inflammation.

Results: Moderate to severe frailty was reported in 52%-97% of recipients depending on the metric. A statistically significant threshold FSI value was identified for each adverse outcome studied. FSI ≥ 14 was associated with decreased survival (88% vs 97% for FSI < 14).

Conclusions: The proposed FSI for ESLD is predictive of poorer outcomes after LT.
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http://dx.doi.org/10.1002/jpen.1729DOI Listing
August 2020

Use of pediatric donor en bloc kidneys along with bladder segment in pediatric liver-kidney and multivisceral-kidney transplantation.

Pediatr Transplant 2020 02 11;24(1):e13596. Epub 2019 Oct 11.

Department of Surgery, Jackson Memorial Hospital, University of Miami Miller School of Medicine, Miami, FL, USA.

The combination of pediatric multivisceral and kidney transplantation leads to additional recipient risks due to the number of anastomoses and to the small sizes of donor structures. The inclusion of donor kidneys, ureters, and a bladder patch en bloc with multivisceral organs decreases the number and complexity of anastomoses and has not yet been reported. Four patients were transplanted in this fashion; three underwent multivisceral-kidney and one underwent liver-kidney transplantation. The first patient was a 3-year-old male with polycystic kidney disease and congenital hepatic fibrosis. The second was a 7-year-old female with complications from necrotizing enterocolitis. The third was a 12-month-old male with megacystis microcolon intestinal hypoperistalsis syndrome and secondary hydronephrosis, and the fourth was a 3-year-old male with multiple intestinal resections secondary to incarcerated hernia. The third patient developed a right ureteral stenosis with an intact bladder patch. The fourth child expired from maintained abdominal sepsis. The first 3 patients maintained normal graft function. There were no cases of thrombosis, arterial stenosis, or urinary leakages. These reported cases demonstrate that small pediatric en bloc transplantation of the multivisceral organs and dual kidneys with a bladder patch anastomosis is a feasible and less complex alternative to the standard procedure.
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http://dx.doi.org/10.1111/petr.13596DOI Listing
February 2020

Visceral arterial embolization prior to multivisceral transplantation in recipient with cirrhosis, extensive portomesenteric thrombosis, and hostile abdomen: Performance and outcome analysis.

Clin Transplant 2019 08 11;33(8):e13645. Epub 2019 Jul 11.

Department of Anesthesia, University of Miami/Jackson Memorial Hospital, Miami, Florida, USA.

Multivisceral transplant (MVT) for cirrhosis, and portomesenteric vein thrombosis (PVT), is fraught with life-threatening thrombo-hemorrhagic complications. Embolization of native viscera has been attempted in a handful of cases with mixed results. We carried out a comparative analysis of angiographic, intra-operative, and pathological findings in three recipients of MVT who were deemed exceptionally high hemorrhagic risk and therefore underwent preoperative visceral embolization. All recipients were male with cirrhosis, PVT, and a surgical history indicative of diffuse visceral adhesions; status post-liver transplantation (n = 2) and proctocolectomy (n = 1). The first patient had two Amplatzer II embolization plugs placed 2 cm from the origins of celiac and superior mesenteric (SMA) arteries. Distal migration of the celiac plug into gastroduodenal artery (GDA) and ensuing ischemia reperfusion injury, presumably contributed to severe disseminated intravascular coagulation (DIC) and intra-operative mortality. In the other two recipients, distal Gelfoam embolization of the SMA, GDA, and splenic arteries was performed, and although remarkable hemorrhage and coagulopathy occurred, embolization, undoubtedly, facilitated exenteration and improved outcomes. Pathologic examination in these cases confirmed ischemic necrosis of eviscerated bowel. In conclusion, liver-sparing, preoperative distal embolization of native viscera with Gelfoam is beneficial, but entails several pitfalls. It should currently be reserved for MVT recipients who otherwise are at unacceptably high risk.
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http://dx.doi.org/10.1111/ctr.13645DOI Listing
August 2019

Liver Transplantation Following Life-threatening Abdominal Trauma: A Case Series of 5 Patients at a Single Institution.

Transplant Proc 2019 Jul - Aug;51(6):1902-1906. Epub 2019 May 30.

Brandon Regional Medical Center, Brandon, FL, United States.

Managing traumatic liver injury (TLI) is always challenging and demands precise clinical judgment. Currently, treatment of TLI in most circumstances is non-operative; however, surgical therapy might be required for severe TLI, particularly those that result in extensive blood loss. In the current institutional study carried out from June 1995 to April 2017, we describe our experience with 5 patients who received an orthotopic liver transplant for severe TLI. One patient passed away postoperatively from cerebral edema; 1 patient died of renal failure 4 years after the liver transplantation, and 3 patients are still alive. Based on our experience, we conclude that in patients with TLI, especially those with uncontrollable bleeding or those who develop liver failure, liver transplantation should be taken into consideration.
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http://dx.doi.org/10.1016/j.transproceed.2019.04.042DOI Listing
December 2019

Bloodstream infection caused by enteric organisms during the first 6 months after intestinal transplant.

Transpl Infect Dis 2019 Jun 27;21(3):e13064. Epub 2019 Mar 27.

Department of Surgery/Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, Florida.

Background: Data on bloodstream infection (BSI) due to enteric organisms are scarce.

Methods: This retrospective study (1/2009-5/2017) was aimed to evaluate the incidence of BSI episodes due to enteric organisms during the first 6 months after intestinal transplant (ITx). Differences between the first (2009-2012) and second period (2013-2017) were evaluated as they differed from each other in the perioperative fungal prophylaxis and immunosuppressive regimen.

Results: Fifty-five adult patients were analyzed. Twenty-eight (51%) patients developed a total of 51 episodes of BSI. Mean time from transplant to BSI was 85.5 ± 58.8 days. The most common organisms were Klebsiella pneumoniae (33%), Enterococcus spp (31%), and Candida spp (18%). Twenty-three (45%) were multidrug resistant. The most common sources were gut translocation (35%), central line infection (20%), and intra-abdominal abscess (14%). Biopsy-proven rejection was associated with 16 (31%) of the BSI episodes. Patients during the first period were more likely to develop BSI (79% vs 41%, P = 0.03). There were more episodes of rejection associated with BSI in the first period (45% vs 14%, P = 0.03). The rate of reoperation into the abdominal cavity within 2 weeks after ITx was higher and the transplant hospital stay was longer among those who developed BSI (P = 0.04 for both).

Conclusions: Half of our patients developed BSI (typically during the first 3 months). Gut translocation was the most common source of BSI. Patients with rejection and/or enteritis should be monitored closely for BSI.
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http://dx.doi.org/10.1111/tid.13064DOI Listing
June 2019

Solid organ transplantation from Zika IgM positive donors: Not always a true positive.

Clin Transplant 2019 03 20;33(3):e13492. Epub 2019 Feb 20.

Department of Medicine/Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida.

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http://dx.doi.org/10.1111/ctr.13492DOI Listing
March 2019

Comparison in outcome with tailored antibiotic prophylaxis postoperatively in pediatric intestinal transplant population.

Pediatr Transplant 2018 11 9;22(7):e13277. Epub 2018 Aug 9.

Pediatric Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida.

BIs are ubiquitous among the pediatric intestinal transplant patient population. Personalizing postoperative prophylaxis antibiotic regimens may improve outcomes in this population. A retrospective analysis of all pediatric patients who underwent intestinal transplantation was evaluated to compare standardized and tailored regimens of antibiotics provided as prophylaxis postoperatively. Patients in the standard group have both shorter time to and higher rate of BIs, which was statistically significant (P < 0.001). Of the children who developed a BI, there was no statistical difference in average times to the development of a second BI (293 vs 119 days, P = 0.211). The tailored group had prolonged times until the development of a MDRO (52.6 vs 63.9 days, P = 0.677). Although not statistically significant, the tailored group had a propensity to present with gram-negative pathogens after transplant as compared to the standard regimen group, which presented with gram-positive pathogens (P = 0.103). Children with a history of an MDRO held a 7.3 (P < 0.01) times more likelihood of death within a year of transplant. A tailored prophylactic antibiotic regimen in the post-transplant period appears to prolong the time to the first BI. Although the data do not show differences in mortality, further study may prove the impact of a tailored antibiotic regimen on morbidity and mortality rates.
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http://dx.doi.org/10.1111/petr.13277DOI Listing
November 2018

Virologic response with 2 different cidofovir dosing regimens for preemptive treatment of adenovirus DNAemia in pediatric solid organ transplant recipients.

Pediatr Transplant 2018 Jun 3:e13231. Epub 2018 Jun 3.

Division of Pediatric Infectious Diseases and Immunology, Department of Pediatrics, Miller School of Medicine-Jackson Health System, University of Miami, Miami, FL, USA.

ADV is frequently seen in our pediatric SOT population. It presents in a variety of clinical presentation and can cause severe disease. In this population, there are very few studies to determine the safety of CDV as a potential therapeutic agent. We present the findings of our retrospective study evaluating the efficacy and safety of CDV as 2 separate dosing regimens. Regimen A uses the standard 5 mg/kg once a week (Regimen A), and the second uses the 1 mg/kg 3 times per week (Regimen B). Overall, the dosing regimen did not differ in nephrotoxicity, but Regimen B had a higher, although non-significant, rate of viral load clearance. This suggests that more frequent dosing at lower levels may be more efficacious without any significant side effects in our SOT population.
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http://dx.doi.org/10.1111/petr.13231DOI Listing
June 2018

Pediatric patient with end-stage kidney disease secondary to Eagle-Barrett syndrome and metastatic unresectable hepatoblastoma treated successfully with chemotherapy and liver-kidney transplant.

Pediatr Transplant 2018 03 22;22(2). Epub 2018 Jan 22.

Department of Pediatrics, University of Miami-Holtz Children's Hospital, Miami, FL, USA.

HBL is the most common malignant liver neoplasm in children. The etiology of HBL is largely unknown but there are certain syndromes, such as Beckwith-Wiedemann syndrome, that have been clearly associated with an increased incidence of this malignancy. EBS, also known as prune belly syndrome, is a congenital anomaly characterized by lax abdominal musculature, bilateral cryptorchidism requiring, in some cases, hemodialysis due to significant kidney and urinary tract dysfunctions. Despite an improvement on the survival rates of patients with advanced-stage HBL, the presence of concomitant end-stage renal disease that occurs in patients with EBS constitutes a therapeutic challenge for the clinician not only due to the use of nephrotoxic chemotherapy but also due to the potential need for multi-organ transplant. We report case of a 2-year-old male patient with EBS diagnosed with stage IV, metastatic HBL successfully treated with multi-agent chemotherapy while on dialysis whom then underwent a simultaneous liver-kidney transplant followed by adjuvant chemotherapy. Ultimately, the patient achieved cancer remission with normalization of his renal function. Our report emphasizes that patients with HBL in the setting of EBS will not only require careful kidney function monitoring while receiving chemotherapy, but they might also need to undergo multi-organ transplantation in order to achieve adequate cancer control and also normalization of their kidney function. Awareness of this unusual association calls for further investigation to potentially establish a genetic association between these two disease processes.
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http://dx.doi.org/10.1111/petr.13123DOI Listing
March 2018

CD52-Negative NK Cells Are Abundant in the Liver and Less Susceptible to Alemtuzumab Treatment.

PLoS One 2016 25;11(8):e0161618. Epub 2016 Aug 25.

Division of Liver and Gastrointestinal Transplantation, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, United States of America.

Background: T-cell depleting strategies have become an integral part of immunosuppressive regimens in organ transplantation. Alemtuzumab is a humanized monoclonal antibody against CD52, a cell-surface antigen on several immune cells. It has been suggested that lymphocyte depletion increases the risk of serious infections. However, this has not been observed with short-term alemtuzumab treatment in an organ transplant setting. For induction therapy using alemtuzumab following liver transplantation, we found that T- and B-cell numbers declined rapidly after alemtuzumab therapy; however, the natural killer (NK) cell number was sustained. NK cells are important effectors of innate immunity. Since the effects of alemtuzumab on NK cell functions, especially those of liver NK cells, are unknown, this study aimed to investigate this in detail.

Methods: To assess the effect of alemtuzumab on NK cells, samples were obtained from 7 organ donors and examined by flow cytometry using Annexin V and propidium iodide. Phenotypical and functional differences within subsets of NK cells with different levels of CD52 expression were determined by flow cytometry and in vitro cytotoxicity assays.

Results: CD52 expression on NK cells was lower than that on other lymphocyte subsets. The liver contained a large number of CD52- NK cells compared with the peripheral blood. In vitro treatment of liver-derived NK cells with alemtuzumab did not result in cell death. In contrast, co-incubation with alemtuzumab induced cell death in peripheral blood mononuclear cells and non-NK cells in the liver. Furthermore, CD52- liver NK cells were more cytotoxic and produced more IFN-γ than CD52+ NK cells after cytokine activation.

Conclusion: The liver contains a large number of CD52- NK cells. These cells are refractory to alemtuzumab and have robust activity. These findings indicate that CD52- NK cells persist and could protect against infection after alemtuzumab-based lymphocyte depletion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161618PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999148PMC
August 2017

Pediatric liver transplantation: predictors of survival and resource utilization.

Pediatr Surg Int 2016 May 21;32(5):439-49. Epub 2016 Mar 21.

Division of Pediatric Surgery, DeWitt-Daughtry Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, 1120 NW 14th Street, Suite 450, Miami, FL, 33136, USA.

Purpose: We sought to identify factors associated with increased resource utilization and in-hospital mortality for pediatric liver transplantation (LT).

Methods: Kids' Inpatient Database (1997-2009) was used to identify cases of LT in patients <20 years old.

Results: Overall, 2905 cases were identified, with an in-hospital survival of 91 %. LT was performed most frequently in < 5 year olds (61 %), females (51 %), and Caucasians (56 %). LT was performed at urban teaching hospitals (97 %) and facilities with children's units (51 %). Indications included pathologic conditions of the biliary tract (44 %) and inborn errors of metabolism (34 %), though unspecified end stage liver disease was the most common (75 %). Logistic regression found higher mortality in children undergoing LT for malignant conditions (odds ratio: 4.8) and acute hepatic failure (OR 3.4). Cases complicated by renal failure (OR 7.7) and complications of LT (OR 2.7) had higher mortality rates. Resource utilization increased for children with renal failure and those with hemorrhage as a complication of LT, p < 0.05.

Conclusion: Hospital survival is predicted by indication and complications associated with LT. Resource utilization increased with renal failure and complications related to LT. Admission length was sensitive to payer status, hospital characteristics, and UNOS region, whereas total costs were unaffected by payer status or hospital type.
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http://dx.doi.org/10.1007/s00383-016-3881-6DOI Listing
May 2016

Abdominal transplantation for unresectable tumors in children: the zooming out principle.

Pediatr Surg Int 2016 Apr 28;32(4):337-46. Epub 2015 Dec 28.

Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.

Purpose: To present our experience in abdominal transplantations to manage unresectable abdominal neoplasms in children and to describe the role of extensive surgeries in such cases.

Methods: This is a retrospective study of 22 abdominal transplantations in 21 patients for abdominal tumors over 16 years. Transplantation techniques included liver transplant (LT), multivisceral transplant (MVTx), and intestinal autotransplant (IA). Follow-up intervals ranged from 0.3 to 168 months (median 20 months).

Results: LT alone was performed in 15 patients for primary malignant (11) and benign (4) liver tumors. Pathological classification included HB hepatoblastoma (6), HCC hepatocellular cancer (3), hepatic epithelioid hemangioendothelioma HEH (1), angiosarcoma (1), benign vascular tumors (3), and adenoma (1). IA was performed in four patients for lesions involving the root of the mesentery; tumors of the head of pancreas (3) and mesenteric hemangioma (1). MVTx was performed in 2 patients for malignancies; pancreaticoblastoma (1), recurrent hepatoblastoma (1), and in one patient as a rescue procedure after IA failure. Four of the eleven patients who underwent LT for malignant liver tumor had metastatic disease at presentation. Six of them died of recurrent neoplasm (3), transplant-related complications (2), and underlying disease (1). All LT patients who had benign tumors are alive with functioning grafts. All IA patients survived and are on an oral diet, with one patient requiring TPN supplementation. One of the three patients who underwent MVTx died of metastatic disease.

Conclusions: Allo/auto transplantation for abdominal tumors is a valuable modality when conventional treatments fail or are not feasible.
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http://dx.doi.org/10.1007/s00383-015-3852-3DOI Listing
April 2016

Unique presentation and endovascular management of arterio-portal fistula after liver transplant.

Pediatr Transplant 2015 Dec 7;19(8):940-1. Epub 2015 Oct 7.

Department of Surgery (Liver and Transplant), Jackson Memorial Hospital, University of Miami, Miami, FL, USA.

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http://dx.doi.org/10.1111/petr.12616DOI Listing
December 2015

Successful Treatment of Carbapenemase-Producing Pandrug-Resistant Klebsiella pneumoniae Bacteremia.

Antimicrob Agents Chemother 2015 Oct;59(10):5903-8

Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain

New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated.
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http://dx.doi.org/10.1128/AAC.00655-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576028PMC
October 2015

Clinical significance of intragraft miR-122 and -155 expression after liver transplantation.

Hepatol Res 2015 Aug 17;45(8):898-905. Epub 2014 Nov 17.

Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

Aim: Recurrent hepatitis C (RHC) and acute cellular rejection (AR) remain critical problems following liver transplantation (LT) in hepatitis C virus (HCV) positive recipients because of the similar clinical features. Discrimination between these conditions can be problematic, and adjunctive biomarkers would be useful to discriminate these processes. The aim of our study was to investigate the possibility of the intragraft miR-122 and -155 expression as new biomarkers after LT.

Methods: A total of 29 HCV positive recipients were enrolled in this study. Intragraft expressions of miR-122 and -155 were studied between RHC predominant (n = 17) and AR predominant cases (n = 12) using quantitative reverse transcription polymerase chain reaction. Furthermore, we investigated the correlations between these expression levels and clinical serum parameters.

Results: Intragraft miR-122 expression had a good correlation with serum alkaline phosphatase (P = 0.02), but it was not correlated with the serum HCV viral load. The expression levels of miR-122 in the AR group were significantly higher than those in the RHC group (P = 0.0006) and, inversely, the expression levels of miR-155 in the AR group were significantly lower than those in the RHC group (P = 0.01).

Conclusion: Our study emphasizes a useful pattern of miR-122 and -155 as ancillary markers to discriminate AR predominant cases from RHC in HCV positive patients after LT.
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http://dx.doi.org/10.1111/hepr.12424DOI Listing
August 2015

Allogeneic uterus transplantation in baboons: surgical technique and challenges to long-term graft survival.

Transplantation 2014 Sep;98(5):e51-6

1 Division of Liver and Intestinal Transplantation Department of Surgery University of Miami School of Medicine Miami, FL 2 Department of Surgery Cleveland Clinic Weston, FL 3 Department of Obstetrics and Gynecology Sahlgrenska Academy University of Gothenburg Göteborg, Sweden 4 The Mannheimer Foundation, Inc. Homestead, FL 5 Department of Pathology Sahlgrenska Academy University of Gothenburg Göteborg, Sweden 6 Department of Anesthesia and Intensive Care Sahlgrenska Academy University of Gothenburg Göteborg, Sweden 7 Department of Gynecology and Obstetrics La Fe University Hospital University of Valencia Valencia, Spain 8 Department of Pathology Cleveland Clinic Weston, FL 9 Department of Gynecology Cleveland Clinic Weston, FL 10 Department of Gynecology Cleveland Clinic Weston, FL 11 Sahlgrenska Transplant Institute, Department of Transplantation, Sahlgrenska Academy University of Gothenburg Göteborg, Sweden.

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http://dx.doi.org/10.1097/TP.0000000000000322DOI Listing
September 2014

Transplantation in autosomal recessive polycystic kidney disease: liver and/or kidney?

Pediatr Nephrol 2015 Aug 13;30(8):1233-42. Epub 2014 Aug 13.

Department of Pediatrics, Division of Pediatric Nephrology, Holtz Children's Hospital, University of Miami Miller School of Medicine, PO Box 016960 (M-714), Miami, FL, 33101, USA,

Autosomal recessive polycystic kidney disease (ARPKD) is characterized by enlarged kidneys with dilated collecting ducts and congenital hepatic fibrosis. There is a variable rate of progression of kidney and liver disease. Portal hypertension and Caroli's disease occur from liver involvement that contributes to morbidity and mortality. Approximately 40 % of patients have a severe disease phenotype leading to rapid onset of end-stage kidney disease (ESKD) and signs of portal hypertension and the rest may have predominant involvement of either the kidney or liver. It is important for the physician to establish the extent of organ involvement before deciding on the ultimate plan of management, especially when transplantation is required. Isolated renal transplantation can be considered when liver involvement is minimal. If hepatobiliary disease is prominent, and kidney function is preserved, management options are based on individual characteristics. In the presence of significant liver disease and ESKD, consideration should be given to combined liver kidney transplantation, which can be beneficial in eliminating the consequences of both kidney and liver disease. However, this is a complex surgical procedure that needs to be performed at experienced transplant centers. Improvement in surgical techniques has considerably improved short-term graft survival with the added advantage of the liver offering immunologic protection to the kidney allograft.
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http://dx.doi.org/10.1007/s00467-014-2887-3DOI Listing
August 2015

When and why portal vein thrombosis matters in liver transplantation: a critical audit of 174 cases.

Ann Surg 2014 Apr;259(4):760-6

*Miami Transplant Institute, University of Miami and Jackson Memorial Hospital, Miami, FL †DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL ‡Department of Pathology, University of Miami Leonard M. Miller School of Medicine Miami, FL §Transplant Center, Carolinas Medical Center, Charlotte, NC ¶Transplant Center, Cleveland Clinic Florida, Weston, FL.

Objective: To identify complications associated with different techniques utilized to treat portal vein thrombosis (PVT) during primary liver transplantation and their impact on survival.

Background: PVT remains an intricate problem in liver transplantation, and the long-term outcomes of patients with PVT who undergo transplantation are not well defined.

Methods: We performed a retrospective cohort analysis of all consecutive adult patients who underwent primary isolated liver transplantation from 1998 to 2009 (median follow-up period, 89 months). The outcomes of patients with PVT were compared with those without PVT.

Results: Among 1379 recipients, 174 (12.6%) had PVT at the time of transplantation [83 (48%) complete and 91 (52%) partial]. Among PVT patients with reestablished physiological portal inflow (PVT: physiological group; n = 149), 123 underwent thrombectomies, 16 received interpositional vein grafts, and 10 received mesoportal jump grafts. In 25 patients, physiological portomesenteric venous circulation was not reconstituted (PVT: nonphysiological group; 18 underwent cavoportal hemitranspositions, 6 renoportal anastomoses, and 1 arterialization). The PVT: nonphysiological group suffered a significantly increased incidence of rethrombosis of the portomesenteric veins and gastrointestinal bleeding, with a marginal 10-year overall survival rate of 42% (no PVT, 61%; P = 0.002 and PVT: physiological, 55%; P = 0.043). The PVT: physiological and no PVT groups exhibited comparable survival rates (P = 0.13). No significant differences in survival were observed between complete and partial PVT as long as physiological portal flow was reestablished.

Conclusions: The subset of PVT patients requiring nonphysiological portal vein reconstruction was associated with higher complication rates and suffered diminished long-term prognoses. For the most severe PVT cases, a comprehensive approach is critical to further improve outcomes.
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http://dx.doi.org/10.1097/SLA.0000000000000252DOI Listing
April 2014

Long-term deleterious effects of aortohepatic conduits in primary liver transplantation: proceed with caution.

Liver Transpl 2013 Aug;19(8):916-25

Miami Transplant Institute, University of Miami/Jackson Memorial Hospital, Miami, FL 33331, USA.

Aortohepatic conduits provide a vital alternative for graft arterialization during liver transplantation. Conflicting results exist with respect to the rates of comorbidities, and long-term survival data on primary grafts are lacking. To identify the complications associated with aortohepatic conduits in primary liver transplantation and their impact on survival, we conducted a single-center, retrospective cohort analysis of all consecutive adult (n = 1379) and pediatric primary liver transplants (n = 188) from 1998 to 2009. The outcomes of aortohepatic conduits were compared to those of standard arterial revascularization. Adults with a conduit (n = 267) demonstrated, in comparison with adults with standard arterialization (n = 1112), an increased incidence of late (>1 month after transplantation) hepatic artery thrombosis (HAT; 4.1% versus 0.7%, P < 0.001) and ischemic cholangiopathy (7.5% versus 2.7%, P < 0.001) and a lower 5-year graft survival rate (61% versus 70%, P = 0.01). The adjusted hazard ratio (HR) for graft loss in the conduit group was 1.38 [95% confidence interval (CI) = 1.03-1.85, P = 0.03]. Notably, the use of conduits (HR = 4.91, 95% CI = 1.92-12.58) and a warm ischemia time > 60 minutes (HR = 11.12, 95% CI = 3.06-40.45) were independent risk factors for late HAT. Among children, the complication profiles were similar for the conduit group (n = 81) and the standard group (n = 107). In the pediatric cohort, although the 5-year graft survival rate for the conduit group (69%) was significantly impaired in comparison with the rate for the standard group (81%, P = 0.03), the use of aortohepatic conduits did not emerge as an independent predictor of diminished graft survival via a multivariate analysis. In conclusion, in adult primary liver transplantation, the placement of an aortohepatic conduit should be strictly limited because of the greater complication rates (notably late HAT) and impaired graft survival; for children, its judicious use may be acceptable.
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http://dx.doi.org/10.1002/lt.23689DOI Listing
August 2013

Lower respiratory tract viral infections in pediatric abdominal organ transplant recipients: a single hospital inpatient cohort study.

Pediatr Transplant 2013 Aug 14;17(5):461-5. Epub 2013 May 14.

Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA.

Respiratory viral infections are a major cause of morbidity and mortality in solid organ transplant recipients. Early detection of a viral etiology of a LRTI in a febrile transplant recipient can theoretically reduce the use of antibiotics, trigger modification of immunosuppression and prompt appropriate isolation procedures to reduce nosocomial infections. We retrospectively evaluated pediatric abdominal organ transplant recipients hospitalized with respiratory illnesses to determine the viral pathogens identified by various methods including multiplex RT-PCR performed on nasopharyngeal or endotracheal aspirates. Among 30 symptomatic subjects (median age, 2.5 yr) evaluated using this methodology, 25 (83%) were positive for at least one virus. Rhinovirus was the most frequently identified virus (14 subjects). RSV was identified in five subjects with associated mortality of 40%. Parainfluenza, influenza, metapneumovirus, and adenovirus were also identified. This study indicates that rhinovirus is a significant cause of morbidity in this single center cohort of pediatric abdominal organ transplant recipients.
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http://dx.doi.org/10.1111/petr.12093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159153PMC
August 2013

Portal vein arterialization using an accessory right hepatic artery in liver transplantation.

Liver Transpl 2013 Jul 3;19(7):773-5. Epub 2013 Jun 3.

Division of Transplantation, Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.

Portal vein thrombosis remains to be a challenging issue during liver transplantation even with the acquisition of innovative surgical techniques and years of experience. Most frequently, an initial eversion thromboendovenectomy is performed and depending on the extent of thrombosis and intraoperative findings, further revascularization options include venous jump grafts, portocaval hemitransposition, renoportal anastomosis or portal vein arterialization. Reports on these surgical approaches are limited although with acceptable outcomes. We present a 64-year-old patient with hepatitis C cirrhosis who underwent orthotopic liver transplantation with portal vein arterialization using an accessory right hepatic artery. Liver graft function has remained stable four years after transplant with notable aneurysmal dilatation of the portal vein.
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http://dx.doi.org/10.1002/lt.23653DOI Listing
July 2013