Higher Incidence of Protein-Losing Enteropathy in Patients with Single Systemic Right Ventricle.

Patients with single ventricle congenital heart disease are at risk of unpredictable protein-losing enteropathy (PLE) after surgical palliation. Based on prior reports of physiologic differences for patients with single morphologic right versus left ventricles, we hypothesized that those with right ventricular morphology would have a higher incidence of PLE. We performed a retrospective review of > 15 million pediatric hospitalizations from the Healthcare Cost and Utilization Project KID 2000-2012 databases for admissions 5-21 years old with ICD-9 codes for hypoplastic left heart syndrome (HLHS) and tricuspid atresia (TA) with and without PLE. Incidence of PLE was compared between those with HLHS and TA. In addition, outcomes and costs were compared between admissions with and without PLE and between HLHS and TA. Of 1623 HLHS admissions, 289 (17.8%) had PLE, and of 926 TA admissions, 58 (5.9%) had PLE (p < 0.001). Admissions with PLE were older compared to those without PLE (12 vs 10 years, p < 0.001) and PLE onset occurred at a younger age for HLHS than TA (11 vs 14 years, p < 0.001). There were no differences in hospital outcomes or costs. Review of this large administrative database suggests a higher incidence of PLE in patients with HLHS and a younger age of onset compared to those with TA. These data suggest that a single systemic right ventricle may be an independent risk factor for developing PLE.

Impact of protein-losing enteropathy in children who underwent the Fontan operation.

Previous reports have identified risk factors associated with development of post-Fontan protein-losing enteropathy. Less is known about the economic impact and resource utilisation required for post-Fontan protein-losing enteropathy in the current era. We conducted a single-centre retrospective study to assess the impact of post-Fontan protein-losing enteropathy on transplant-free survival. We also described resource utilisation and treatment variations among post-Fontan protein-losing enteropathy patients. Children who received care at our centre between 2009 and 2017 after the Fontan surgery were eligible. Initial admissions for the Fontan operative procedure were excluded. Demographics, hospital admissions, resource utilisation, medications and charges were reviewed. Patients were divided into two groups based on the presence of post-Fontan protein-losing enteropathy. Of the 343 patients screened, 147 met the eligibility criteria. Of these, 28 (19%) developed protein-losing enteropathy. After adjusting for follow-up duration, the protein-losing enteropathy group had higher number of encounters (2.15 ± 2.16 versus 1.47 ± 2.56, p 0.002), hospital length of stay (days) (25 ± 51.3 versus 11.4 ± 41.7, p < 0.0001) and total charges (2018US$) (388,489 ± 759,859 versus 202,725 ± 1,076,625, p < 0.0001). Encounters for patients with protein-losing enteropathy utilised more therapies. Among those with protein-losing enteropathy, use of digoxin was associated with slightly decreased odds for mortality and/or transplant (0.95, confidence interval 0.90-0.99, p 0.021). The 10-year transplant-free survival for patients with/without protein-losing enteropathy was 65.7/97.3% (p 0.002), respectively. Post-Fontan protein-losing enteropathy is associated with reduced 10-year transplant-free survival, higher resource utilisation, charges and medication use compared with the non-protein-losing enteropathy group. Practice variation among post-Fontan protein-losing-enteropathy patients is common. Further larger studies are needed to assess the impact of standardisation on the well-being of children with post-Fontan protein-losing enteropathy.

Prevalence of Subclinical Enteric Alpha-1-Antitrypsin Loss in Children with Univentricular Circulation Following Total Cavopulmonary Connection.

Protein-Losing Enteropathy post Fontan palliation is associated with significant morbidity and mortality. To date, very little research has been carried out to improve early identification of enteric protein loss in these patients. We hypothesise that subclinical enteric protein loss may occur in patients post Fontan surgery. A cross-sectional study was performed on 43 patients post Fontan surgery. We collected specimens of stool and blood from patients with no symptoms of protein-losing enteropathy post Fontan. Stool samples were assessed for alpha one antitrypsin. The stool samples of two patients were discarded, leaving 41 stool samples. Blood samples were also collected to review albumin, C-reactive protein, liver and renal function. Twenty-eight (65%) of those enrolled were male. The median (IQR) age between Fontan and collection of study specimens was 3.5 (2-7) years. Two (5%) patients had elevated levels of alpha-1-antitrypsin. There was no correlation between blood biochemistry and elevated stool alpha-1-antitrypsin. Subclinical protein loss is rare in asymptomatic children after Fontan procedure with only 5% of patients having elevated stool alpha-1-antitrypsin but no other symptoms. These findings may relate to our small cohort size and the time to testing post cardiac surgery. Future longitudinal follow-up studies should assess the ability of alpha-1-antitrypsin to provide earlier detection of protein-losing enteropathy in asymptomatic patients post Fontan. Given the serious prognosis of protein-losing enteropathy in this patient group, further work is warranted.

Proposal for Prevention or Alleviation of Protein/Lymph-Losing Enteropathy (PLE/LLE) After Fontan Circulation Treatment of Univentricular Hearts: Restoration of Lymph Balance With a "Lymphatic Right-to-Left Shunt."

In Fontan circulations created for univentricular hearts, systemic venous return is diverted to the lungs before returning to the heart. The Total Cavopulmonary Connection (TCPC) is often the preferred surgical procedure whereby a 4-way anastomosis is created with inflow from the superior vena cava (SVC) and inferior vena cava (IVC) and outflow to the right and left branches of the pulmonary artery. In this arrangement, the systemic venous pressure must be elevated sufficiently to perfuse the lungs passively without the normal boost of the right ventricle. Hence, unlike surgical corrections for other congenital heart conditions, the systemic venous pressures in a Fontan circuit must be elevated to make the circulation work. It is proposed here that the incidence of PLE/LLE is directly related to elevated venous and lymphatic pressures, which cause leakage of proteins/lymph into the gastrointestinal tract (GIT) and expulsion from the body. It is commonly held that elevated venous pressures are relatively better tolerated in the upper body, but much less so in the heptatosplanchnic circulation and the lower body. It is also well established that elevated venous pressure increases lymph formation, most of which is produced in the hepatosplanchnic region (liver and intestine). It is further argued here that the increase in lymph filling pressure arising from the higher lymph flow, in association with the backpressure exerted by elevated venous pressure at the main drainage point into the venous system, results in a substantial increase in pressure in the thoracic duct. This pressure is transmitted back to the intestinal lymphatics, causing dilatation with lacteal rupture and protein or bulk lymph leakage into the intestine. We propose in this paper a new approach, based on experimental evidence, to prevent and/or alleviate this condition by draining or redirecting the thoracic duct (or, alternatively, a more localized intestinal lymphatic vessel) into one of the pulmonary veins or the left atrium, which are typically at near-normal pressure in a Fontan circulation. This "lymphatic-venous right-to-left" shunt maneuver would significantly reduce the venous backpressure on the lymphatics as well as improve lymph circulation, resulting in a decrease in the intestinal lymphatic pressure and thereby prevent or alleviate protein/lymph loss, i.e. lymph balance would be restored. Moreover, the greatly facilitated lymphatic flow would encourage further capillary filtration to relieve excessive venous pressure in the hepatosplanchnic region and protect the liver and kidneys. This paper is intended as a discussion document for elicitation of comments on the soundness and viability of this proposal as well as on technical challenges and steps to explore and advance it.

Low serum 25-hydroxyvitamin D levels and secondary hyperparathyroidism in Fontan patients.

BACKGROUND: Limited data exist on the vitamin D status in Fontan patients. We determined the prevalence and potential risk factors of vitamin D deficiency in this patient subset. Methods and results Data were collected from 27 Fontan patients (55.6% male, mean age 8.1±5.3 years). Protein-losing enteropathy was diagnosed in six patients (22.2%). Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D level of <20 ng/ml. The neutrophil-to-lymphocyte ratio, a marker of systemic inflammation, was calculated. Associations between laboratory measurements and patient characteristics were explored. Mean serum 25-hydroxyvitamin D level was 14.1±10.4 ng/ml. Vitamin D deficiency was found in 19/27 patients (70.3%). Only skin type was associated with vitamin D deficiency (p=0.04). Hyperparathyroidism was present in 5/21 (23.8%) patients, and was more prevalent in patients with protein-losing enteropathy (p<0.001). Parathyroid hormone levels correlated with parameters of systemic inflammation (neutrophil-to-lymphocyte ratio: r=0.484, p=0.026; relative lymphocyte count: r=-0.635, p=0.002). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D levels (p<0.0001), and was accompanied by a reduction in parathyroid hormone concentrations (p=0.032). CONCLUSIONS: A high prevalence of vitamin D deficiency was found among Fontan patients, independent of age, time after Fontan procedure, ventricular morphology, and presence of protein-losing enteropathy. A potentially important link between parathyroid hormone levels and systemic inflammation is suggested.

Fontan-associated protein-losing enteropathy and plastic bronchitis.

OBJECTIVE: To characterize the medical history, disease progression, and treatment of current-era patients with the rare diseases Fontan-associated protein-losing enteropathy (PLE) and plastic bronchitis. STUDY DESIGN: A novel survey that queried demographics, medical details, and treatment information was piloted and placed online via a Facebook portal, allowing social media to power the study. Participation regardless of PLE or plastic bronchitis diagnosis was allowed. Case control analyses compared patients with PLE and plastic bronchitis with uncomplicated control patients receiving the Fontan procedure. RESULTS: The survey was completed by 671 subjects, including 76 with PLE, 46 with plastic bronchitis, and 7 with both. Median PLE diagnosis was 2.5 years post-Fontan. Hospitalization for PLE occurred in 71% with 41% hospitalized ≥ 3 times. Therapy varied significantly. Patients with PLE more commonly had hypoplastic left ventricle (62% vs 44% control; OR 2.81, 95% CI 1.43-5.53), chylothorax (66% vs 41%; OR 2.96, CI 1.65-5.31), and cardiothoracic surgery in addition to staged palliation (17% vs 5%; OR 4.27, CI 1.63-11.20). Median plastic bronchitis diagnosis was 2 years post-Fontan. Hospitalization for plastic bronchitis occurred in 91% with 61% hospitalized ≥ 3 times. Therapy was very diverse. Patients with plastic bronchitis more commonly had chylothorax at any surgery (72% vs 51%; OR 2.47, CI 1.20-5.08) and seasonal allergies (52% vs 36%; OR 1.98, CI 1.01-3.89). CONCLUSIONS: Patient-specific factors are associated with diagnoses of PLE or plastic bronchitis. Treatment strategies are diverse without clear patterns. These results provide a foundation upon which to design future therapeutic studies and identify a clear need for forming consensus approaches to treatment.

Incidence of relapse of inflammatory protein-losing enteropathy in dogs and associated risk factors.

BACKGROUND: Dogs with inflammatory protein-losing enteropathy (iPLE) that attain remission may be at risk of subsequent relapse. OBJECTIVES: To determine the incidence of relapse of iPLE in dogs that have previously attained complete clinical and biochemical remission and identify associated risk factors. ANIMALS: Seventy-five client-owned dogs diagnosed with iPLE. METHODS: Medical records of dogs diagnosed with iPLE based on histopathology of intestinal biopsy specimens between March 2010 and March 2020 were retrospectively reviewed. Variables were recorded from the time of investigation at histopathologic diagnosis and subsequent follow-up information was obtained from the records of referring veterinarians. RESULTS: Twenty-three dogs (31%) achieved sustained remission without documentation of relapse for at least 2 years. Nineteen dogs (25%) achieved remission, but then subsequently relapsed within 2 years of histopathologic diagnosis, and 33 dogs (44%) never achieved remission with disease-associated death occurring a median of 19 (range, 3-114) days after histopathologic diagnosis. Dogs that achieved remission and subsequently relapsed had significantly higher poor dietary compliance, as defined by frequent scavenging or changing from the recommended diet compared to dogs with sustained remission (P = .01). CONCLUSIONS: Inflammatory PLE is associated with a high rate of relapse in dogs. Ensuring owners adhere to dietary recommendations might help prevent subsequent relapse in dogs with iPLE that attain initial remission.

Gastrointestinal and hepatic manifestations of systemic lupus erythematosus.

In this review of the gastrointestinal (GI) and hepatic manifestations of systemic lupus erythematosus (SLE), 180 articles from the English literature, found using a medline search from January 1965 to December 2010, were examined. Vasculitis may cause ulcerations, bleeding, stricture formation, and perforation from ischemia and infarction. Otherwise, GI symptoms, occurring in about 50% of patients, are usually mild. Esophageal dysmotility may result in heartburn, regurgitation, and dysphagia. Occasionally, pneumatosis cystoides intestinalis may develop, sometimes associated with benign pneumoperitoneum. Patients are prone to salmonella bacteremia, presenting more commonly with fever and abdominal pain than with diarrhea. Intestinal pseudoobstruction usually is found with active lupus serology, preferentially involving small rather than the large bowel. Protein-losing enteropathy, characterized by diarrhea, edema, and hypoalbuminemia, can be the initial presentation of SLE. Malabsorption with a prevalence of 9.5% is occasionally associated with celiac disease. Pancreatitis, with an annual incidence of 0.4 to 1/1000, has an overall mortality of 27% that is decreased with corticosteroid therapy. Acute and chronic ascites may be due to lupus peritonitis or to associated diseases, such as pancreatitis, nephrotic syndrome, heart failure, or infections. Abnormal liver function tests may be due to steatosis from lupus or from corticosteroid therapy. Only about 10% of patients with autoimmune hepatitis have lupus. Up to 4.7% of patients with SLE have chronic active hepatitis correlating strongly with the presence of antibody to ribosomal P protein. SLE can involve the entire GI tract and the liver. Treatment with corticosteroids, cytotoxic agents, and/or immunosuppressants is often successful.

Protein-losing enteropathy and plastic bronchitis after the Fontan procedure.

OBJECTIVES: Protein losing enteropathy and plastic bronchitis are severe complications in Fontan circulation, with 5-year survival ranging from 46% to 88%. We report risk factors and outcomes of protein losing enteropathy and plastic bronchitis in patients undergoing the Fontan. METHODS: We performed a retrospective analysis of 1561 patients from the Australia New Zealand Fontan Registry. Two end points were death and cardiac transplantation examined with Cox regression (if no competing risks) or cumulative incidence curves and cause-specific Cs regression. RESULTS: A total of 55 patients with protein losing enteropathy/plastic bronchitis were included. Their median age at the Fontan was 5.7 years, and time to onset after the Fontan for protein losing enteropathy was 5.0 years and plastic bronchitis was 1.7 years. Independent predictors for developing protein losing enteropathy/plastic bronchitis were right-ventricular morphology with hypoplastic left-heart syndrome (hazard ratio, 2.30; confidence interval, 1.12-4.74), older age at Fontan (hazard ratio, 1.13; confidence interval, 1.03-1.23), and pleural effusions after Fontan (hazard ratio, 2.43; confidence interval, 1.09-5.41); left-ventricular morphology was protective (hazard ratio, 0.36; confidence interval, 0.18-0.70). In the protein losing enteropathy/plastic bronchitis population, freedom from death or transplantation after protein losing enteropathy/plastic bronchitis diagnosis at 5, 10, and 15 years was 70% (confidence interval, 58-85), 65% (confidence interval, 51-83), and 43% (confidence interval, 26-73), respectively; only older age (hazard ratio, 1.23; confidence interval, 1.01-1.52) was an independent predictor. Twenty-six surgical interventions were performed in 20 patients, comprising Fontan revisions (n = 5), fenestrations (n = 11), Fontan conversions (n = 5), atrioventricular valve repairs (n = 3), and hepatic vein diversion (n = 2). CONCLUSIONS: Protein losing enteropathy and plastic bronchitis remain severe complications, preferably affecting patients with dominant right single ventricle, with older age at Fontan being a predictor of developing protein losing enteropathy/plastic bronchitis and poorer prognosis. Heart transplantation remains the ultimate treatment, with 30% dying or requiring transplantation within 5 years, and the remaining being stable for long periods.

Major gastrointestinal manifestations in lupus patients in Asia: lupus enteritis, intestinal pseudo-obstruction, and protein-losing gastroenteropathy.

Gastrointestinal (GI) symptoms are common in patients with systemic lupus erythematosus (SLE) and may be due to the disease itself, side-effects of medications, or non-SLE causes. However, GI manifestations of lupus attract far less attention than the other major organ involvements, are infrequently reviewed and rarely documented in published lupus databases or cohort studies including those from countries in Asia. According to three reports from two countries in Asia, the cumulative prevalence of SLE GI manifestations range from 3.8% to 18%. In this review, we focus on three major GI manifestations in patients from Asian countries: lupus enteritis, intestinal pseudo-obstruction, and protein-losing gastroenteropathy, for which early recognition improves outcome and reduces morbidity and mortality.

Fontan-associated protein-losing enteropathy and post‒heart transplant outcomes: A multicenter study.

BACKGROUND: The influence of Fontan-associated protein-losing enteropathy's (PLE) severity, duration, and treatment on heart transplant (HTx) outcomes is unknown. We hypothesized that long-standing PLE and PLE requiring more intensive therapy are associated with increased post-HTx mortality. METHODS: This 12-center, retrospective cohort study of post-Fontan patients with PLE referred for HTx from 2003 to 2015 involved collection of demographic, medical, surgical, and catheterization data, as well as PLE-specific data, including duration of disease, intensity/details of treatment, hospitalizations, and complications. Factors associated with waitlist and post-HTx outcomes and PLE resolution were sought. RESULTS: Eighty patients (median of 5 per center) were referred for HTx evaluation. Of 68 patients listed for HTx, 8 were removed due to deterioration, 4 died waiting, and 4 remain listed. In 52 patients undergoing HTx, post-HTx 1-month survival was 92% and 1-year survival was 83%. PLE-specific factors, including duration of PLE pre-HTx, pre-HTx hospitalizations, need for/frequency of albumin replacement, PLE therapies, and growth parameters had no association with post-HTx mortality. Immunosuppressant regimen was associated with mortality; standard mycophenolate mofetil immunotherapy was used in 95% of survivors compared with only 44% of non-survivors (p = 0.03). Rejection (53%) and infection (42%) post-HTx were common, but not associated with PLE-specific factors. PLE resolved completely in all but 1 HTx survivor at a median of 1 month (interquartile range 1 to 3 months); resolution was not affected by PLE-specific factors. CONCLUSIONS: PLE severity, duration, and treatment do not influence post-HTx outcome, but immunosuppressive regimen may have an impact on survival. PLE resolves in nearly all survivors.

Lupus-associated protein-losing enteropathy.

Fourteen cases of primary lupus-associated protein-losing enteropathy have now been reported in the English-language literature. These cases were reviewed to find any consistent pattern of presentation. Lupus-associated protein-losing enteropathy typically occurs in young women, and is characterized by the onset of profound edema and hypoalbuminemia. In many cases it is the first obvious manifestations of systemic lupus erythematosus. Diarrhea is present about 50% of the time, but steatorrhea is absent. Diagnosis of protein-losing enteropathy can be successfully made by radioisotopic studies or 24-hour stool alpha 1-antitrypsin clearance. A normal lymphocyte count, elevated serum cholesterol, and absence of lymphangiectasia on intestinal biopsy help distinguish lupus-associated protein-losing enteropathy from protein-losing enteropathies due to direct or indirect lymphatic obstruction. Normal endoscopy and mucosal biopsy can rule out protein loss due to mucosal disruption. Prognosis appears to be excellent with corticosteroids, although other immunosuppressive therapies have been successfully used. A typical and illustrative case is presented as a focal point for review and discussion.

Fecal alpha 1-antitrypsin and hemoglobin excretion in healthy human milk-, formula-, or cow's milk-fed infants.

There is concern that whole cow's milk feedings may be associated with intestinal abnormalities in infants. We studied this issue by measuring random fecal samples for alpha 1-antitrypsin (FA1AT) and hemoglobin (FH) concentrations in 820 healthy infants up to 12 months of age. Subjects were fed either human milk, formula, or fresh whole cow's milk. Solid foods were given ad libitum. Fecal samples were also tested for occult blood with Hematest reagent tablets. None of the infants younger than 6 months of age were receiving fresh whole cow's milk. We found small but statistically significant differences in mean FA1AT between the three feeding groups (P less than .0001): human milk (n = 354) greater than formula (n = 320) greater than cow's milk (n = 146). The younger subjects fed either formula or human milk tended to have higher FA1AT concentrations than did the age-matched subjects who were not consuming solid foods (P less than or equal to .005). Daily FA1AT excretion, FA1AT concentration, and daily stool output were subsequently determined on a separate group of 40 infants 8 to 12 months of age to ascertain whether differences in total daily FA1AT excretion occur in children fed different types of milk. Total daily FA1AT excretion was similar in the three milk feeding groups. An inverse correlation between FA1AT concentration and daily stool output was also found (P less than .001). The overall rate of detectable FH in 792 stool smears was 2.1% and unrelated to type of milk feeding. Of 705 stool smears, 3.5% had positive Hematest reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein-losing enteropathy after the Fontan operation: an international multicenter study. PLE study group.

OBJECTIVE: This multicenter study retrospectively analyzes the data on 114 patients with protein-losing enteropathy after Fontan-type surgery. Special attention was given to the different treatment strategies used and their effect on outcome. METHODS AND RESULTS: In 35 participating centers 3029 Fontan operations were performed. The incidence of protein-losing enteropathy in the survivors was 3.7%. The median age at Fontan-type surgery was 8.2 years (range: 0.6 to 32.9 years). Median age at diagnosis of protein-losing enteropathy was 11.7 years with a median time interval between surgery and diagnosis of 2.7 years (range: 0.1 to 16.4 years). Most patients had edema (79%) and effusions (75%). Hemodynamic data revealed a mean right atrial pressure of 17 +/- SD 5.3 mm Hg with a cardiac index of 2.4 +/- 0.8 L/min/m2. Medical treatment only (n = 52) resulted in a complete resolution of symptoms in 25%, no improvement in 29%, and death in 46%. Surgical treatment (n = 52) was associated with relief of protein-losing enteropathy in 19%, no improvement in 19%, and death in 62%. In 13 patients 16 percutaneous interventions were performed. This resulted in symptomatic improvement after 12 interventions and no improvement after 4 interventions. CONCLUSIONS: We conclude that the current treatment of protein-losing enteropathy after Fontan operation is associated with a very high mortality and morbidity rate. Preventive strategies and new therapeutic approaches are necessary.

Protein-losing enteropathy after fontan surgery: is assessment of risk patients with immunological data possible?

BACKGROUND: Protein-losing enteropathy (PLE) is a late complication of the Fontan type surgery for univentricular heart characterized by massive enteric protein loss. The pathogenesis of PLE is not fully understood, and it is unclear why the onset of PLE varies widely and occurs months or even years after surgery. Besides characteristic laboratory findings, a typical cellular feature concerns the almost selective loss of CD4(+) lymphocytes at an only slightly changed CD8(+) lymphocyte count. The present pilot study aimed to test whether immunological or laboratory parameters differ in patients at risk for PLE. METHODS: From children (n = 15) with Fontan type circulation, extensive cellular, humoral, and clinical laboratory data were analyzed. Patients without enteric protein loss (group I, n = 8), with transient phases of enteric protein loss in the absence of gastric infections (group II, n = 6), and one PLE patient (group III) were distinguished. The 90 data columns obtained in phases with normal serum protein levels were compared. RESULTS: Clear differences were apparent between patients prior to PLE onset (group III), patients that in at least one occasion exhibited PLE signs (group II), and patients without detectable PLE signs (group I). The most discriminatory parameters between the three patient groups were NK and CD8(+)TCRalphabeta(+), CD8(+)TCRgammadelta(+) cell counts, including sL-selectin, IgE, and Ca(2+) (average recognition index = 91.5%, negative/positive prediction/sensitivity/specificity > 83%). CONCLUSIONS: The results of this study seem to provide access to the early detection of PLE patients.

Social media methods for studying rare diseases.

For pediatric rare diseases, the number of patients available to support traditional research methods is often inadequate. However, patients who have similar diseases cluster "virtually" online via social media. This study aimed to (1) determine whether patients who have the rare diseases Fontan-associated protein losing enteropathy (PLE) and plastic bronchitis (PB) would participate in online research, and (2) explore response patterns to examine social media's role in participation compared with other referral modalities. A novel, internet-based survey querying details of potential pathogenesis, course, and treatment of PLE and PB was created. The study was available online via web and Facebook portals for 1 year. Apart from 2 study-initiated posts on patient-run Facebook pages at the study initiation, all recruitment was driven by study respondents only. Response patterns and referral sources were tracked. A total of 671 respondents with a Fontan palliation completed a valid survey, including 76 who had PLE and 46 who had PB. Responses over time demonstrated periodic, marked increases as new online populations of Fontan patients were reached. Of the responses, 574 (86%) were from the United States and 97 (14%) were international. The leading referral sources were Facebook, internet forums, and traditional websites. Overall, social media outlets referred 84% of all responses, making it the dominant modality for recruiting the largest reported contemporary cohort of Fontan patients and patients who have PLE and PB. The methodology and response patterns from this study can be used to design research applications for other rare diseases.

Low pulmonary vascular compliance predisposes post-Fontan patients to protein-losing enteropathy.

BACKGROUND: Protein-losing enteropathy (PLE) is a life-threatening and poorly understood complication after the Fontan operation. We sought to determine the pre-operative risk factors for PLE which developed after the extracardiac conduit Fontan operation. METHODS: Two hundred thirty-five patients who underwent the extracardiac conduit Fontan operation as an initial Fontan type procedure (median age at operation: 3.5 years) were enrolled in this cross-sectional retrospective study. Pre-operative and peri-operative variables were surveyed through a review of medical records. RESULTS: Within the median follow-up duration of 5 years, 12 patients developed PLE (12/234, 5.1%) at a median interval of 2.2 years after the Fontan procedure, and 4 died of PLE at a median interval of 1.2 years (range 0.21-7.62) after diagnosis. Factors found to be related to the time to the development of PLE on univariate analysis were pulmonary vascular compliance (Cpv) (p=0.0019), central venous pressure at postoperative 12 hours (p=0.0026), days of ICU stay (P=0.0449), days of hospitalization (p=0.0135), and days of chest tube indwelling (p=0.0493). Multivariate analysis, however, showed that only Cpv (p=0.0367) remained significant. The range of Cpv was 8.8-26.1 mm(2)/m(2)/mmHg (median 17.9) in patients with PLE, and 6.6-122.3 mm(2)/m(2)/mmHg (median 26.8) in patients without PLE. CONCLUSIONS: Low pulmonary vascular compliance is associated with the development of PLE after the extracardiac conduit Fontan operation.

Prevalence of perinuclear antineutrophilic cytoplasmic autoantibodies in serum of healthy Soft Coated Wheaten Terriers in the United Kingdom.

OBJECTIVE: To estimate the prevalence of perinuclear antineutrophilic cytoplasmic autoantibodies (pANCA) in the serum of healthy Soft Coated Wheaten Terriers (SCWTs) in the United Kingdom and to identify potential risk factors and heritability patterns associated with a positive result for pANCA. ANIMALS: 188 SCWTs (age range, 18 months to 14.3 years). PROCEDURES: Blood samples were obtained from SCWTs in various locations in England. Serum was tested for pANCA by use of an immunofluorescence assay, and total protein and albumin concentrations were determined. Pedigrees were evaluated to identify close relatives that had protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN). RESULTS: 39 of 188 (20.7%) dogs, including young dogs, had positive results for pANCA. Dogs had significantly higher odds of having positive results for pANCA if they had at least 1 littermate that had PLE or PLN (odds ratio, 12.1) or if they had at least 1 full sibling from another litter known to be affected with PLE or PLN (odds ratio, 4.0). CONCLUSIONS AND CLINICAL RELEVANCE; This study revealed a high prevalence of pANCA in the serum of a representative sample of healthy SCWTs in the United Kingdom and a significant association between positive results for pANCA and a diagnosis of PLE or PLN in a sibling.