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

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.

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

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.

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

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.

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

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.

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

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.

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.

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.

Intravenous Acetaminophen for Postoperative Pain Management in Patients Undergoing Living Laparoscopic Living-Donor Nephrectomy.

BACKGROUND: Postoperative pain is a common complication of laparoscopic living-donor nephrectomies (LLDNs). OBJECTIVE: To determine whether intravenous (IV) acetaminophen administration post-LLDN influenced length of stay (LOS) when used for pain management. METHODS: This single-center, retrospective study compared patients undergoing LLDN who had received IV acetaminophen for pain control versus those who did not between June 1, 2011, and November 30, 2015. Patient LOS, 30-day readmissions, frequency of pain assessments, patient-reported pain scores, and opioid administration were assessed. RESULTS: A total of 90 patients were included in the analysis (IV acetaminophen, n = 48; non-IV acetaminophen, n = 42). Patients who did not receive IV acetaminophen were more often older (48.8 ± 12.1 vs 39.3 ± 12.1 years; P = 0.012) and female (71.4% vs 47.9%; P < 0.001). The average LOS was similar between the 2 groups (median = 3.0; interquartile range = [3, 4] vs 3.5 [3, 4]; P = 0.737). The 30-day readmissions were higher in the IV acetaminophen group (16.7%) compared with the group not receiving IV acetaminophen (2.4%; P = 0.033). After the first postoperative day, the frequencies of pain assessments performed were similar among the 2 groups. There was no difference in average pain scores between the groups at any time after LLDN. CONCLUSIONS: Patients receiving IV acetaminophen were found to have no improvements in hospital LOS, average pain score, or opioid requirements compared with patients not receiving IV acetaminophen. Patients who received IV acetaminophen were also found to have a higher 30-day readmission rate.

Evaluation of Posttransplantation Diabetes Mellitus After Liver Transplantation: Assessment of Insulin Administration as a Risk Factor.

BACKGROUND: Impaired glucose regulation posttransplantation can affect allograft survival and may lead to the development of posttransplant diabetes mellitus (PTDM). OBJECTIVES: The primary purpose of this study is to assess the difference in insulin burden between liver transplant patients who develop PTDM and patients who do not. METHODS: This was a single-center, retrospective study. Adult liver transplant recipients transplanted between January 1, 2005, and August 1, 2013, were included. PTDM was defined as: (1) use of an oral antihyperglycemic agent for ≥30 consecutive days after transplant, (2) use of insulin ≥30 consecutive days after transplant, or (3) hemoglobin A1C≥6.5 any time after transplant. RESULTS: Of the 114 patients included, 48 (42%) developed PTDM. The average 24-hour insulin requirement on the medical floors was 17.2 ± 14.5 units in the PTDM group and 11.3 ± 12.2 units in the PTDM-free group;P= 0.02. The average blood glucose level on the medical floor was 184.7 ± 31.5 mg/dL in the PTDM group and 169.3 ± 31.4 mg/dL in the PTDM-free group;P= 0.013. Multivariate analysis revealed that experiencing rejection was positively associated with the development of PTDM: adjusted odds ratio (AOR) = 3.237; 95% CI = 1.214-8.633. Basiliximab was negatively associated with the development of PTDM: AOR = 0.182; 95% CI = 0.040-0.836. CONCLUSION: Univariate analyses suggest that insulin burden is a positive risk factor for the development of PTDM; this association is lost in multivariate analyses. Rejection was a positive predictor, and use of basiliximab was a negative predictor for the development of PTDM.

The utility of recanalized umbilical vein graft to the hepato-pancreato-biliary surgeon.

BACKGROUND: The authors recently published their experience of recanalizing umbilical veins in deceased liver donors, with recanalized umbilical veins as vascular conduits for meso-Rex bypass procedures. They have since found recanalized umbilical veins to be an excellent, easy to harvest vascular conduit that can be used for multiple vascular procedures and repair. Here, they report their experience using this vessel for bypass and vascular reconstruction. METHODS: They have recanalized umbilical veins and used them in a total of 5 Meso-Rex bypasses; 5 pancreaticoduodenectomies; 1 left hepatic trisegmentectomy with right portal vein (PV) resection and reconstruction; 1 right hepatectomy and 1 adrenalectomy, both with partial inferior vena cava (IVC) resection and reconstruction; 1 coronary-Rex bypass shunt for extrahepatic PV thrombosis; and 1 orthotopic liver transplantation with infrahepatic IVC anastomotic dehiscence patched with umbilical vein graft. Umbilical veins were dilated mechanically and used in situ for the meso-Rex bypass surgery; they were ligated in the space of Rex and then dilated ex vivo otherwise to be used as interposition grafts or a vein patch. RESULTS: A total of 15 hepato-pancreato-biliary procedures were done using the recanalized umbilical vein as graft; 2 patients required thrombectomy postoperatively with reexploration, venotomy, thrombectomy with fogarty catheter, and venotomy closure. CONCLUSION: The umbilical vein graft is a fine vascular conduit and can serve many purposes in hepatobiliary surgery.

Stereotactic body radiation therapy in hepatocellular carcinoma and cirrhosis: evaluation of radiological and pathological response.

BACKGROUND: Loco-regional therapies for cirrhotic patients with hepatocellular carcinoma (HCC) who are awaiting liver transplantation (OLT) attempt to prevent tumor progression. However, there is limited data regarding the efficacy of stereotactic body radiation therapy (SBRT) as loco-regional treatment. METHODS: From 2006 to 2009, 27 HCC patients (AJCC I, II) listed for OLT underwent SBRT. Thirty-nine lesions were treated and 27 assessed radiologically. Seventeen patients had OLT, liver explants were analyzed and 22 lesions underwent pathological evaluation. RESULTS: In a cumulative analysis of all imaging, 30% had complete response, 7% had partial response, 56% were stable, and 7% had progression of disease. Of the 22 pathologically evaluated lesions, 37% were responders: 14% with complete response, 23% with partial response, and 63% with no response. Side effects from SBRT were recorded in three patients, which included nausea in two and liver decompensation in one. CONCLUSION: SBRT achieves total or partial radiological response in 37% of patients and total or partial pathological response in 37% of patients with early HCC in the setting of cirrhosis. SBRT may be a safe and effective alternative for local tumor control in patients with HCC and cirrhosis awaiting OLT.

Can we direct organ allocation based on predicted outcome? Hepatocellular carcinoma outside of UCSF criteria or retransplant?

BACKGROUND: In this study, we ask between patients with graft failure listed for retransplant and patients with hepatocellular carcinoma (HCC) outside of UCSF criteria, who has the greater survival benefit with transplantation? METHODS: This is a retrospective analysis, of liver transplant (LT) patients, done between February 2002 and December 2009 at our center. Patients were included in the "extended HCC" group if their tumor was pathologically beyond UCSF criteria at LT and in the "redo" group if they underwent LT for graft failure occurring more than 3 months after the initial LT. Extended criteria donors (ECDs) were defined as donors above 70 years old, DCD, serology positive for HCV, and split grafts. RESULTS: There were 25 redos and 37 extended HCC patients. Use of ECDs or high donor risk index organs was associated with poor outcome in both groups (P = 0.005). Overall, the extended HCC population had a much better survival than redos, both at 1 and 3 years. CONCLUSION: These two very different but high risk patient populations have very different survival rates. At a time where regulatory agencies demand more and more with regards to transplant outcomes, we think the transplant community has to reflect on whether allocation justice and fair access to transplant are respected if we start allocating organs based on outcomes.

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

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 m2. 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.

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

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.

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

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.

Compound Effect of Kidney Donor Profile Index and Cold Ischemic Time on 1-Year Kidney Transplant Recipient Outcomes.

OBJECTIVE: Kidney Donor Profile Index (KDPI) and cold ischemic time (CIT) independently influence recipient outcomes after kidney transplantation; however, the compound effect of these variables on posttransplant outcomes is unknown. DESIGN: The Scientific Registry of Transplant Recipients database of deceased-donor kidney transplant recipients between January 2012 and December 2016 was reviewed. Recipients were stratified based on their KDPI (0%-20%, 21%-85%, 86%-100%) and then based on CIT (0-12, 13-24, 25-30, 31-36, ≥ 37 hours). The primary outcome is 1-year allograft loss. Secondary outcomes include primary nonfunction, delayed graft function, biopsy-proven rejection, and 1-year recipient mortality. RESULTS: Allograft loss was not affected by CIT for KDPI 0% to 20% (P = .898) or KDPI 86% to 100% (P = .731), but was significantly different for KDPI 21% to 85% (P < .001). The KDPI 21% to 85% group was the only group with a significant difference in primary nonfunction, demonstrating a linear rise with increasing CIT (P < .001). CIT did not affect recipient mortality for any KDPI group (KDPI 0%-20%, P = .306; KDPI 21%-85%, P = .098; KDPI 86%-100%, P = .774). Incidence of delayed graft function was greater for each KDPI group (P < .001) with increased CIT. Biopsy-proven rejection was not affected by CIT for KDPI 21% to 85% (P = .244) or KDPI 86% to 100% (P = .946). For KDPI 0% to 20%, there was a significant difference (P = .024); however, the incidence was not linear with increasing CIT. For the KDPI 86% to 100% group, incidence of mortality, allograft loss, primary nonfunction, and biopsy-proven rejection did not differ between CIT groups. CONCLUSIONS: Extended CIT alone should not hinder utilization of higher KDPI organs.

Clostridium paraputrificum septicemia and liver abscess.

We report the first case of a healthy 23-year-old female who underwent an interventional radiology-guided embolization of a hepatic adenoma, which resulted in a gas forming hepatic liver abscess and septicemia by Clostridium paraputrificum. A retrospective review of Clostridial liver abscesses was performed using a PubMed literature search, and we found 57 clostridial hepatic abscess cases. The two most commonly reported clostridial species are C. perfringens and C. septicum (64.9% and 17.5% respectively). C. perfringens cases carried a mortality of 67.6% with median survival of 11 h, and 70.2% of the C. perfringens cases experienced hemolysis. All C. septicum cases were found to have underlying liver malignancy at the time of the presentation with a mortality of only 30%. The remaining cases were caused by various Clostridium species, and this cohort's clinical course was significantly milder when compared to the above C. perfringens and C. septicum cohorts.