Ryan P. Cauley

Deceased-Donor Split-Liver Transplantation in Adult Recipients: Is the Learning Curve Over?

BACKGROUND Infants have the highest wait-list mortality of all liver transplantation candidates. Deceased-donor split-liver transplantation, a technique that provides both an adult and pediatric graft, might be the best way to decrease this disproportionate mortality. Yet concern for an increased risk to adult split recipients has discouraged its widespread adoption. We aimed to determine the current risk of graft failure in adult recipients after split-liver transplantation. STUDY DESIGN United Network for Organ Sharing data from 62,190 first-time adult recipients of deceased-donor liver transplants (1995-2010) were analyzed (889 split grafts). Bivariate risk factors (p < 0.2) were included in Cox proportional hazards models of the effect of transplant type on graft failure. RESULTS Split-liver recipients had an overall hazard ratio of graft failure of 1.26 (p < 0.001) compared with whole-liver recipients. The split-liver hazard ratio was 1.45 (p < 0.001) in the pre-Model for End-Stage Liver Disease era (1995-2002) and 1.10 (p = 0.28) in the Model for End-Stage Liver Disease era (2002-2010). Interaction analyses suggested an increased risk of split-graft failure in status 1 recipients and those given an exception for hepatocellular carcinoma. Excluding higher-risk recipients, split and whole grafts had similar outcomes (hazard ratio = 0.94; p = 0.59). CONCLUSIONS The risk of graft failure is now similar between split and whole-liver recipients in the vast majority of cases, which demonstrates that the expansion of split-liver allocation might be possible without increasing the overall risk of long-term graft failure in adult recipients. Additional prospective analysis should examine if selection bias might account for the possible increase in risk for recipients with hepatocellular carcinoma or designated status 1.

Deceased Donor Liver Transplantation in Infants and Small Children: Are Partial Grafts Riskier Than Whole Organs?

Infants have the highest wait‐list mortality of all liver transplant candidates. Although previous studies have demonstrated that young children may be at increased risk when they receive partial grafts from adult and adolescent deceased donors (DDs), with few size‐matched organs available, these grafts have increasingly been used to expand the pediatric donor pool. We aimed to determine the current adjusted risks of graft failure and mortality in young pediatric recipients of partial DD livers and to determine whether these risks have changed over time. We analyzed 2683 first‐time recipients of DD livers alone under the age of 24 months in the United Network for Organ Sharing database (1995‐2010), which included 1118 partial DD livers and 1565 whole DD organs. Transplant factors associated with graft loss in bivariate analyses (P < 0.1) were included in multivariate proportional hazards models of graft and patient survival. Interaction analysis was used to examine risks over time (1995‐2000, 2001‐2005, and 2006‐2010). Although there were significant differences in crude graft survival by the graft type in 1995‐2000 (P < 0.001), graft survival rates with partial and whole grafts were comparable in 2001‐2005 (P = 0.43) and 2006‐2010 (P = 0.36). Furthermore, although the adjusted hazards for partial graft failure and mortality were 1.40 [95% confidence interval (CI) = 1.05‐1.89] and 1.41 (95% CI = 0.95‐2.09), respectively, in 1995‐2000, the adjusted risks of graft failure and mortality were comparable for partial and whole organs in 2006‐2010 [hazard ratio (HR) for graft failure = 0.81, 95% CI = 0.56‐1.18; HR for mortality = 1.02, 95% CI = 0.66‐1.71]. In conclusion, partial DD liver transplantation has become less risky over time and now has outcomes comparable to those of whole liver transplantation for infants and young children. This study supports the use of partial DD liver grafts in young children in an attempt to significantly increase the pediatric organ pool. Liver Transpl 19:721–729, 2013..

Avoiding Breast Animation Deformity with Pectoralis-Sparing Subcutaneous Direct-to-Implant Breast Reconstruction

Summary: There is renewed interest in sparing the pectoralis major muscle in implant breast reconstruction, placing the implant in the subcutaneous position. This advance is made reliable by improvements in mastectomy skin flap quality, evolution of technique, and increased awareness of breast animation deformity. This retrospective review presents 13 patients (23 breasts) reconstructed immediately with placing the definitive implant in the subcutaneous space without disruption of the underlying chest muscles. None of the 13 patients had breast animation deformity postoperatively. One patient experienced an early hematoma, and 3 patients had small seromas that resolved uneventfully. One morbidly obese patient undergoing chemotherapy using a nearby chest port experienced infection requiring implant removal. This study describes an early experience, demonstrates feasibility, and discusses patient selection considerations that are important because we continue to evolve breast reconstruction approaches.

Nutritional outcomes in survivors of congenital diaphragmatic hernia (CDH)-factors associated with growth at one year.

BACKGROUND Malnutrition is prevalent among congenital diaphragmatic hernia (CDH) survivors. We aimed to describe the nutritional status and factors that impact growth over the 12-months following discharge from the pediatric intensive care unit (PICU) in this cohort. METHODS CDH survivors, who were discharged from the PICU from 2000 to 2010 with follow-up of at least 12months, were included. Nutritional intake, anthropometric, and clinical variables were recorded. Multivariable linear regression was used to determine factors associated with weight-for-age Z-scores (WAZ) at 12months. RESULTS Data from 110 infants, 67% male, 50% patch repair, were analyzed. Median (IQR) WAZ for the cohort was -1.4 (-2.4 to -0.3) at PICU discharge and -0.4 (-1.3 to 0.2) at 12-months. The percentage of infants with significant malnutrition (WAZ<-2) decreased from 26% to 8.5% (p<0.001). Patch repair (p=0.009), protein intake<2.3g/kg/day (p=0.014), and birth weight (BW)<2.5kg (p<0.001) were associated with lower WAZ at 12-months. CONCLUSIONS CDH survivors had a significantly improved nutritional status in the 12-months after PICU discharge. Patch repair, lower BW, and inadequate protein intake were significant predictors of lower WAZ at 12-months. A minimum protein intake in the PICU of 2.3g/kg/day was essential to ensure optimal growth in this cohort.

Pulmonary support on Day 30 as a predictor of morbidity and mortality in congenital diaphragmatic hernia

PURPOSE Congenital diaphragmatic hernia (CDH) is associated with significant in-hospital mortality, morbidity and length-of-stay (LOS). We hypothesized that the degree of pulmonary support on hospital day-30 may predict in-hospital mortality, LOS, and discharge oxygen needs and could be useful for risk prediction and counseling. METHODS 862 patients in the CDH Study Group registry with a LOS ≥ 30 days were analyzed (2007-2010). Pulmonary support was defined as (1) room-air (n=320) (2) noninvasive supplementation (n=244) (3) mechanical ventilation (n=279) and (4) extracorporeal membrane oxygenation (ECMO, n=19). Cox Proportional hazards and logistic regression models were used to determine the case-mix adjusted association of oxygen requirements on day-30 with mortality and oxygen requirements at discharge. RESULTS On multivariate analysis, use of ventilator (HR 5.1, p=.003) or ECMO (HR 19.6, p<.001) was a significant predictor of in-patient mortality. Need for non-invasive supplementation or ventilator on day-30 was associated with a respective 22-fold (p<.001) and 43-fold (p<.001) increased odds of oxygen use at discharge compared to those on room-air. CONCLUSIONS Pulmonary support on Day-30 is a strong predictor of length of stay, oxygen requirements at discharge and in-patient mortality and may be used as a simple prognostic indicator for family counseling, discharge planning, and identification of high-risk infants.

Polyspike and waves do not predict generalized tonic-clonic seizures in childhood absence epilepsy.

About 40% of children with childhood absence epilepsy develop generalized tonic-clonic seizures. It is commonly held that polyspike—wave pattern on the electroencephalogram (EEG) can predict this development of generalized tonic-clonic seizures. However, there is no firm evidence in support of this proposition. To test this assumption, we used survival analysis and compared the incidence of generalized tonic-clonic seizures in 115 patients with childhood absence epilepsy having either isolated 3-Hz spike—wave or coexisting 3 Hz and polyspike—waves and other variables. There was no evidence that polyspike—waves predicted development of generalized tonic-clonic seizures in patients with childhood absence epilepsy. Later age of onset (≥8 years) and family histories of generalized tonic-clonic seizures were the only independent predictors. These results have implications for counseling and in the choice of first-line antiepileptic drugs used for childhood absence epilepsy, especially if valproate is chosen based on the observation of polyspike—waves.

Immediate extubation after pediatric liver transplantation: A single‐center experience

The care of pediatric liver transplant recipients has traditionally included postoperative mechanical ventilation. In 2005, we started extubating children undergoing liver transplantation in the operating room according to standard criteria for extubation used for general surgery cases. We reviewed our single‐center experience to determine our rates of immediate extubation and practice since that time. The records of 84 children who underwent liver transplantation from 2005 to 2011 were retrospectively reviewed. The immediate extubation rate increased from 33% during 2005‐2008 to 67% during 2009‐2011. Immediate extubation did not result in an increased reintubation rate in comparison with delayed extubation in the intensive care unit (ICU). Patients undergoing immediate extubation had a trend toward a shorter mean ICU stay as well as a significantly decreased overall hospital length of stay. Our findings suggest that there is a learning curve for instituting immediate extubation in the operating room after liver transplantation and that the majority of pediatric liver recipients can safely undergo immediate extubation. Liver Transpl 21:57‐62, 2015.

Aorto‐Mesenteric and Renal Allograft Transplant: A Novel Treatment for Midaortic Syndrome

Midaortic syndrome (MAS) is a rare condition characterized by stenosis of the aorta and often involving renal and visceral arteries. Current therapies include medical management of associated hypertension, and interventional procedures such as angioplasty or surgical bypass. We report a 2‐year‐old female with severe MAS who was initially treated with angioplasty and stents in both her aorta and superior mesenteric artery (SMA). Due to the presence of long segment stenoses, her renal arteries were not amenable to surgical reconstruction and she rapidly progressed to Stage V chronic kidney disease. The patient underwent bilateral nephrectomy and renal transplantation using a donor thoracoabdominal aorta allograft to provide inflow for the kidney as well as to bypass the nearly occluded aorta. The donor SMA was used to bypass the native SMA stenosis. Postoperatively, the patient had normalization of four limb blood pressures. She weaned from five anti‐hypertensive agents to monotherapy with excellent renal function. This is the first reported case of thoracoabdominal aortic bypass using allograft aorta to address MAS. This approach allowed for successful kidney transplantation with revascularization of the mesenteric, and distal aortic circulation using allograft conduit that will grow with the child, obviating the need for repeated interventional or surgical procedures.

Pulmonary support on day of life 30 is a strong predictor of increased 1 and 5-year morbidity in survivors of congenital diaphragmatic hernia.

PURPOSE Pulmonary support (PS) on day-of-life-30 (DOL-30) has been shown to be the strongest predictor of subsequent morbidity and in-patient mortality in congenital diaphragmatic hernia (CDH). We hypothesized that PS on DOL-30 can also predict long-term outcomes in CDH survivors. METHODS We analyzed records of 201 CDH survivors followed by a single multidisciplinary clinic (1995-2010). Follow-up was 83 and 70% at 1 and 5years respectively. PS was defined as: (1) invasive support (n=44), (2) noninvasive support (n=54), or (3) room air (n=103). Logistic regression was used to estimate the adjusted association of PS on DOL-30 with outcomes at 1 and 5-years. RESULTS Use of PS on DOL-30 was significantly associated with pulmonary and developmental morbidities at 1 and 5-years. Even after adjusting for defect-size and presence of ventilation/perfusion mismatch, greater PS on DOL-30 was associated with a significantly increased odds of requiring supplemental oxygen and developmental referral at 1-year, and asthma and developmental referral at 5-years. CONCLUSION CDH survivors continue to have significant long-term pulmonary and developmental morbidities. PS on DOL-30 is a strong independent predictor of morbidity at 1 and 5-years and may be used as a simple prognostic tool to identify high-risk infants.

Long term mortality in critically ill burn survivors

INTRODUCTION Little is known about long term survival risk factors in critically ill burn patients who survive hospitalization. We hypothesized that patients with major burns who survive hospitalization would have favorable long term outcomes. METHODS We performed a two center observational cohort study in 365 critically ill adult burn patients who survived to hospital discharge. The exposure of interest was major burn defined a priori as >20% total body surface area burned [TBSA]. The modified Baux score was determined by age + %TBSA+ 17(inhalational injury). The primary outcome was all-cause 5year mortality based on the US Social Security Administration Death Master File. Adjusted associations were estimated through fitting of multivariable logistic regression models. Our final model included adjustment for inhalational injury, presence of 3rd degree burn, gender and the acute organ failure score, a validated ICU risk-prediction score derived from age, ethnicity, surgery vs. medical patient type, comorbidity, sepsis and acute organ failure covariates. Time-to-event analysis was performed using Cox proportional hazard regression. RESULTS Of the cohort patients studied, 76% were male, 29% were non white, 14% were over 65, 32% had TBSA >20%, and 45% had inhalational injury. The mean age was 45, 92% had 2nd degree burns, 60% had 3rd degree burns, 21% received vasopressors, and 26% had sepsis. The mean TBSA was 20.1%. The mean modified Baux score was 72.8. Post hospital discharge 5year mortality rate was 9.0%. The 30day hospital readmission rate was 4%. Patients with major burns were significantly younger (41 vs. 47 years) had a significantly higher modified Baux score (89 vs. 62), and had significantly higher comorbidity, acute organ failure, inhalational injury and sepsis (all P<0.05). There were no differences in gender and the acute organ failure score between major and non-major burns. In the multivariable logistic regression model, major burn was associated with a 3 fold decreased odds of 5year post-discharge mortality compared to patients with TBSA<20% [OR=0.29 (95%CI 0.11-0.78; P=0.014)]. The adjusted model showed good discrimination [AUC 0.81 (95%CI 0.74-0.89)] and calibration (Hosmer-Lemeshow χ2 P=0.67). Cox proportional hazard multivariable regression modeling, adjusting for inhalational injury, presence of 3rd degree burn, gender and the acute organ failure score, showed that major burn was predictive of lower mortality following hospital admission [HR=0.34 (95% CI 0.15-0.76; P=0.009)]. The modified Baux score was not predictive for mortality following hospital discharge [OR 5year post-discharge mortality=1.00 (95%CI 0.99-1.02; P=0.74); HR for post-discharge mortality=1.00 (95% CI 0.99-1.02; P=0.55)]. CONCLUSIONS Critically ill patients with major burns who survive to hospital discharge have decreased 5year mortality compared to those with less severe burns. ICU Burn unit patients who survive to hospital discharge are younger with less comorbidities. The observed relationship is likely due to the relatively higher physiological reserve present in those who survive a Burn ICU course which may provide for a survival advantage during recovery after major burn.