Kristina Potanos

Fragile X-associated tremor/ataxia syndrome in sisters related to X-inactivation.

Fragile X tremor/ataxia syndrome (FXTAS) is a recently described condition consisting of tremor, ataxia, parkinsonism, and executive dysfunction, presenting predominantly in male carriers of a fragile X mental retardation 1 premutation. In this report, we present premutation carrier sisters in whom severity of clinical signs correlated with a molecular pattern of X‐inactivation favoring higher expression of the premutation allele. In these women with a common genetic background, we suggest that symptom severity may be dictated by X‐inactivation, and thus a higher percentage of cells producing the premutation‐containing mRNA result in increased toxicity and disease. Ann Neurol 2005;57:144–147

Report of 111 Consecutive Patients Enrolled in the International Serial Transverse Enteroplasty (STEP) Data Registry: A Retrospective Observational Study

BACKGROUND The International Serial Transverse Enteroplasty (STEP) Data Registry is a voluntary online database created in 2004 to collect information on patients undergoing the STEP procedure. The aim of this study was to identify preoperative factors that are significantly associated with transplantation or death or attainment of enteral autonomy after STEP. STUDY DESIGN Data were collected from September 2004 to January 2010. Univariate and multivariate logistic regression analyses were applied to determine the predictors of transplantation or death or enteral autonomy post-STEP. Time to reach full enteral nutrition was estimated using a Kaplan-Meier curve. RESULTS Fourteen of the 111 patients in the Registry were excluded due to inadequate follow-up. Of the remaining 97 patients, 11 patients died and 5 progressed to intestinal transplantation. On multivariate analysis, higher direct bilirubin and shorter pre-STEP bowel length were independently predictive of progression to transplantation or death (p = 0.05 and p < 0.001, respectively). Of the 78 patients who were 7 days of age or older and required parenteral nutrition at the time of STEP, 37 (47%) achieved enteral autonomy after the first STEP. Longer pre-STEP bowel length was also independently associated with enteral autonomy (p = 0.002). Median time to reach enteral autonomy based on Kaplan-Meier analysis was 21 months (95% CI, 12-30). CONCLUSIONS Overall mortality post-STEP was 11%. Pre-STEP risk factors for progressing to transplantation or death were higher direct bilirubin and shorter bowel length. Among patients who underwent STEP for short bowel syndrome, 47% attained full enteral nutrition post-STEP. Patients with longer pre-STEP bowel length were significantly more likely to achieve enteral autonomy.

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..

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.

A Novel Treatment for the Midaortic Syndrome

In a 3-year-old girl with the midaortic syndrome, a tissue expander was used to induce longitudinal growth of the distal aorta over a period of 9 months. It was then possible to resect the stenotic segment and perform an end-to-end anastomosis of the normal portions of aorta.

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.

Reno-portal anastomosis as an approach to pediatric kidney transplantation in the setting of inferior vena cava thrombosis.

In pediatric renal transplantation in the setting of IVC thrombosis, the retrohepatic IVC or gonadal veins are often used for outflow. However, if use of systemic venous outflow is unsuccessful, options become limited. We report the use of the portal vein for venous outflow in kidney retransplantation in the setting of IVC thrombosis. The patient is a 19‐month‐old male who developed end‐stage renal failure at seven months of age secondary to hypotension after spontaneous rupture of an accessory renal vein. The IVC was occluded during emergent laparotomy, and the patient developed extensive IVC thrombosis. The first two transplant attempts used the retrohepatic IVC for venous outflow. Despite good initial flow, in both instances the renal vein thrombosed on post‐operative day 1. In an unsuccessful salvage attempt of the second transplant, a reno‐portal anastomosis was performed. With few options for vascular access, a third transplant was attempted. The reno‐portal stump from the second transplant was used for outflow. The patient recovered well from his third transplant (creatinine 0.6 mg/dL 35 months post‐surgery), demonstrating that the portal vein can be used for outflow in cases of extensive IVC thrombosis.