Preclinical Study of DCD and Normothermic Perfusion for Visceral Transplantation.

Considering recent clinical and experimental evidence, expectations for using DCD-derived intestines have increased considerably. However, more knowledge about DCD procedure and long-term results after intestinal transplantation (ITx) is needed. We aimed to describe in detail a DCD procedure for ITx using normothermic regional perfusion (NRP) in a preclinical model. Small bowel was obtained from pigs donors after 1 h of NRP and transplanted to the recipients. Graft Intestinal samples were obtained during the procedure and after transplantation. Ischemia-reperfusion injury (Park-Chiu score), graft rejection and transplanted intestines absorptive function were evaluated. Seven of 8 DCD procedures with NRP and ITx were successful (87.5%), with a good graft reperfusion and an excellent recovery of the recipient. The architecture of grafts was well conserved during NRP. After an initial damage of Park-chiu score of 4, all grafts recovered from ischemia-reperfusion, with no or very subtle alterations 2 days after ITx. Most recipients (71.5%) did not show signs of rejection. Only two cases demonstrated histologic signs of mild rejection 7 days after ITx. Interestingly intestinal grafts showed good absorptive capacity. The study's results support the viability of intestinal grafts from DCD using NRP, contributing more evidence for the use of DCD for ITx.

[Cost-effectiveness of universal childhood vaccination against hepatitis A in Spain: a dynamic approach]. / Coste-efectividad de la vacunación universal infantil frente a la hepatitis A en España: un enfoque dinámico.

OBJECTIVE: To evaluate the cost-effectiveness of infant universal vaccination against hepatitis A in Spain. METHOD: Using a dynamic model and decision tree model, a cost-effectiveness analysis was performed to compare three vaccination strategies against hepatitis A: non-vaccination strategy versus universal childhood vaccination of hepatitis A with one or two doses. The perspective of the study was that of the National Health System (NHS) and a lifetime horizon was considered. Both costs and effects were discounted at 3% per year. Health outcomes were measured in terms of quality adjusted life years (QALY) and the cost-effectiveness measure used was the incremental cost-effectiveness ratio (ICER). In addition, deterministic sensitivity analysis by scenarios was performed. RESULTS: In the particular case of Spain, with low endemicity for hepatitis A, the difference in health outcomes between vaccination strategies (with 1 or 2 doses) and non-vaccination are practically non-existent, terms of QALY. In addition, the ICER obtained is high, exceeding the limits of willingness to pay from Spain (€22,000-25,000/QALY). The deterministic sensitivity analysis showed that the results are sensitive to the variations of the key parameters, although in no case the vaccination strategies are cost-effective. CONCLUSIONS: Universal infant vaccination strategy against hepatitis A would not be a cost-effective option from the NHS perspective in Spain.

Familial CD45RA- T cells to treat severe refractory infections in immunocompromised patients.

Background: Immunocompromised patients are susceptible to high-risk opportunistic infections and malignant diseases. Most antiviral and antifungal drugs are quite toxic, relatively ineffective, and induce resistance in the long term. The transfer of pathogen-specific Cytotoxic T-Lymphocytes has shown a minimal toxicity profile and effectiveness in treating Cytomegalovirus, Adenovirus, Epstein - Barr virus, BK Virus and Aspergillus infections, but this therapy have the main limitations of regulatory issues, high cost, and absence of public cell banks. However, CD45RA- cells containing pathogen-specific memory T-cells involve a less complex manufacturing and regulatory process and are cheaper, feasible, safe, and potentially effective. Methods: We present preliminary data from six immunocompromised patients: four who had severe infectious diseases and two who had EBV lymphoproliferative disease. All of them underwent multiple safe familial CD45RA- T-cell infusions as adoptive passive cell therapy, containing Cytomegalovirus, Epstein - Barr virus, BK virus, and Aspergillus-specific memory T-cells. We also present the method for selecting the best donors for CD45RA- cells in each case and the procedure to isolate and store these cells. Results: The infusions were safe, there was no case of graft-versus host disease, and they showed a clear clinical benefit. The patients treated for BK virus nephritis, Cytomegalovirus encephalitis, Cytomegalovirus reactivation, and disseminated invasive aspergillosis experienced pathogen clearance, complete resolution of symptoms in 4-6 weeks and a lymphocyte increase in 3 of 4 cases after 3-4 months. Donor T cell transient microchimerism was detected in one patient. The two patients treated for EBV lymphoproliferative disease underwent chemotherapy and several infusions of CD45RA- memory T-cells containing EBV cytotoxic lymphocytes. Donor T-cell microchimerism was observed in both patients. The viremia cleared in one of the patients, and in the other, despite the viremia not clearing, hepatic lymphoproliferative disease remained stable and was ultimately cured with EBV-specific Cytotoxic T-Lymphocytes. Conclusion: The use of familial CD45RA- T-cells containing specific Cytotoxic T-lymphocytes is a feasible, safe and potential effective approach for treating severe pathogen infections in immunocompromised patients through a third party donor. Furthermore, this approach might be of universal use with fewer institutional and regulatory barriers.

First case report of multivisceral transplant from a deceased cardiac death donor.

The current shortage of pediatric multivisceral donors accounts for the long time and mortality on the waiting list of pediatric patients. The use of donors after cardiac death, especially after the outbreak of normothermic regional perfusion, has increased in recent years for all solid organs except the intestine, mainly because of its higher susceptibility to ischemia-reperfusion injury. We present the first literature case of multivisceral donors after cardiac death transplantation in a 13-month-old recipient from a 2.5-month-old donor. Once exitus was certified, an extracorporeal membrane oxygenation circuit was established, cannulating the aorta and infrarenal vena cava, while the supra-aortic branches were clamped. The abdominal organs completely recovered from ischemia through normothermic regional perfusion (extracorporeal membrane oxygenation initially and beating heart later). After perfusion with the preservation solution, the multivisceral graft was uneventfully implanted. Two months later, the patient was discharged without any complications. This case demonstrates the possibility of reducing the time spent on the waiting list for these patients.

Native Spleen Preservation During Visceral Transplantation Inhibits Graft-Versus-Host-Disease Development: Clinical and Experimental Study.

OBJECTIVE: We aimed to assess whether native spleen preservation during visceral transplantation (VT) affects graft-versus-host-disease (GVHD) incidence. SUMMARY BACKGROUND DATA: GVHD is one of the most severe and frequently lethal hematological complications after VT procedures. Because there is no specific treatment for GVHD, it is imperative to develop a strategy to reduce donor lymphocyte engraftment and proliferation. METHODS: Our study included both clinical and experimental data. A total of 108 patients were divided into 3 groups: a native spleen preservation group, a native spleen removal with no donor spleen group, and a donor spleen included (allogeneic spleen) group. We also used an allogeneic VT rat model, in which recipients were divided into 2 groups: a native spleen preservation (+SP) group and a native spleen removal (-S) group. Skin rash appearance, histopathological changes, chimerism, and spleen effects on circulating allogeneic T-cells were assessed. RESULTS: The patients with native spleen preservation showed a lower rate of GVHD ( P <.001) and better survival ( P <.05) than those in the other groups. Skin and histological signs of GVHD were lower in the rats in the +SP group ( P <.05). The donor T-cell frequency in the bloodstream and skin was also significantly reduced when the native spleen was preserved ( P <.01 and P <.0001, respectively). CONCLUSIONS: The clinical and experimental data indicate that recipient spleen preservation protects against GVHD after VT, and donor cell clearance from the bloodstream by spleen macrophages could be the underlying mechanism. Therefore, spleen preservation should be considered in VT procedures, whenever possible.

Coste-efectividad de la vacunación universal infantil frente a la hepatitis A en España: un enfoque dinámico / Cost-effectiveness of universal childhood vaccination against hepatitis A in Spain: a dynamic approach

Objetivo: Evaluar el coste-efectividad de diferentes estrategias de vacunación universal infantil frente a la hepatitis A en España. Método: A partir de un modelo dinámico y un árbol de decisión, se realizó un análisis de coste-efectividad para comparar tres estrategias de vacunación frente a la hepatitis A: no vacunación y vacunación universal infantil con una y dos dosis. La perspectiva del estudio escogida fue la del Sistema Nacional de Salud (SNS) y se consideró como horizonte temporal toda la vida del paciente. Tanto los costes como los efectos se descontaron al 3% anual. Los resultados en salud se midieron en años de vida ajustados por calidad (AVAC) y la medida de coste-efectividad utilizada es la razón de coste-efectividad incremental (RCEI). Además, se llevaron a cabo análisis de sensibilidad determinísticos por escenarios. Resultados: En el caso particular de España, con baja endemicidad de hepatitis A, las diferencias en resultados en salud entre las distintas estrategias de vacunación (con una o dos dosis) y la no vacunación son prácticamente inexistentes, en términos de AVAC. Además, las RCEI obtenidas son elevadas, superando los límites establecidos de disposición a pagar obtenidos en España (22.000-25.000 €/AVAC). El análisis de sensibilidad determinístico muestra que los resultados son sensibles a las variaciones de los parámetros clave, aunque en ningún caso resultan coste-efectivos. Conclusiones: La vacunación universal infantil frente a la hepatitis A no sería una opción coste-efectiva desde la perspectiva del SNS en España en la actualidad. (AU)

Objective: To evaluate the cost-effectiveness of infant universal vaccination against hepatitis A in Spain. Method: Using a dynamic model and decision tree model, a cost-effectiveness analysis was performed to compare three vaccination strategies against hepatitis A: non-vaccination strategy versus universal childhood vaccination of hepatitis A with one or two doses. The perspective of the study was that of the National Health System (NHS) and a lifetime horizon was considered. Both costs and effects were discounted at 3% per year. Health outcomes were measured in terms of quality adjusted life years (QALY) and the cost-effectiveness measure used was the incremental cost-effectiveness ratio (ICER). In addition, deterministic sensitivity analysis by scenarios was performed. Results: In the particular case of Spain, with low endemicity for hepatitis A, the difference in health outcomes between vaccination strategies (with 1 or 2 doses) and non-vaccination are practically non-existent, terms of QALY. In addition, the ICER obtained is high, exceeding the limits of willingness to pay from Spain (€22,000–25,000/QALY). The deterministic sensitivity analysis showed that the results are sensitive to the variations of the key parameters, although in no case the vaccination strategies are cost-effective. Conclusions: Universal infant vaccination strategy against hepatitis A would not be a cost-effective option from the NHS perspective in Spain. (AU)

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study.

Background: The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods: Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings: Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation: Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae. Funding: ISCIII, UNESPA, CIBERES, FEDER, ESF.

First multivisceral transplantation in Mitchell-Riley/Martinez-Frias syndrome.

BACKGROUND: MRS/MFS is a rare multisystem disorder with a poor prognosis. The high mortality rate of this syndrome is related to the severity of the associated gastrointestinal, pancreatic, and hepatobiliary conditions, as most of them are not amenable to conventional medical and surgical treatments. METHODS: We report the case of a Romani girl with all the key clinical features of MRS/MFS, and a review of cases reported in the literature. Our patient is a newborn from consanguineous parents who presented duodenal atresia, hypoplastic pancreas, gallbladder agenesis, and neonatal diabetes. Given the clinical suspicion of MRS/MFS, a genetic analysis was performed which revealed the presence of a homozygous variant in the RFX6 gene. During the course of the disease, the patient presented intractable secretory diarrhea and severe intestinal failure. RESULTS: At 2 years of age, she underwent MVT of the stomach, duodenum, small intestine, colon, liver, and pancreas. There were no surgical complications. Histologic evaluation of the small bowel showed extensive patches of gastric heterotopia. After more than 10 years of follow-up, she had presented with normal gastrointestinal, hepatic, and pancreatic function. She has one of the longest survival periods in the literature. CONCLUSIONS: Our experience suggests that multivisceral transplantation may be a promising option in select cases of MRS/MFS.

Deploying unsupervised clustering analysis to derive clinical phenotypes and risk factors associated with mortality risk in 2022 critically ill patients with COVID-19 in Spain.

BACKGROUND: The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes. METHODS: Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 ICUs in Spain. The objective was to utilize an unsupervised clustering analysis to derive clinical COVID-19 phenotypes and to analyze patient's factors associated with mortality risk. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves. RESULTS: The database included a total of 2022 patients (mean age 64 [IQR 5-71] years, 1423 (70.4%) male, median APACHE II score (13 [IQR 10-17]) and SOFA score (5 [IQR 3-7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the A (mild) phenotype (537; 26.7%) included older age (< 65 years), fewer abnormal laboratory values and less development of complications, B (moderate) phenotype (623, 30.8%) had similar characteristics of A phenotype but were more likely to present shock. The C (severe) phenotype was the most common (857; 42.5%) and was characterized by the interplay of older age (> 65 years), high severity of illness and a higher likelihood of development shock. Crude ICU mortality was 20.3%, 25% and 45.4% for A, B and C phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications. CONCLUSION: The presented machine learning model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a "one-size-fits-all" model in practice.

Current status of pediatric intestinal transplant in Europe.

PURPOSE OF REVIEW: This review features articles published during 2018 and 2019 regarding pediatric visceral transplantation in Europe. In this biannual review, the authors identify and summarize key articles pertinent to clinical and research areas. RECENT FINDINGS: There is a trend to a lower use of intestinal transplantation in pediatric population in Europe. Most articles were focused in long-term follow-up. The burden of the disease 10 years after intestinal transplantation is still significant, including the need of several medications, readmissions, and the need of specific follow-up, mostly because of psychiatric problems. Regarding eating behaviors, promoting eating pretransplant may be protective and there may be eating difficulty predictors that could be used to facilitate targeted interventions. Two different articles were consistent in the identification of C1q-fixing DSA as a marker of poor outcome, and capillaritis was identified as a predictor of C4d positivity in intestinal graft biopsies. The inclusion of the liver emerged as the main protective factor against dnDSA development. The incidence of PTLD (specially the monomorphic type) was significantly higher following ITx than after LTx (14.9 vs. 2.8%). The European societies and the EU have made an effort to promote networking, collaborative registries, and sharing of knowledge in pediatric transplantation. SUMMARY: Recent articles focused mostly on long-term follow-up issues, although translational research has also been sustained by some groups.

Pitfalls in Diagnosis of Early-Onset Inflammatory Bowel Disease.

AIM: The onset of inflammatory bowel disease (IBD) in patients younger than the age of 5 years is rare. Moreover, when there is exclusive colonic inflammation, diagnosis can be challenging. Our aim was to describe the difficulties and pitfalls in the diagnosis of early-onset IBD (eoIBD) and their repercussions in treatment decisions. PATIENTS AND METHODS: Patients with eoIBD (Crohn's disease [CD], ulcerative, and unclassified colitis) treated at our center between 1990 and 2016 were studied retrospectively. Demographic, clinical, medical, and surgical treatment data were analyzed. RESULTS: A total of 19 patients were diagnosed with eoIBD at 21 (1-46) months of age. Bloody diarrhea, growth failure, and abdominal pain were present in 90, 42, and 16%, respectively. After 9 (1-62) months from the onset, patients were classified as ulcerative colitis (nine), CD (two), and unclassified colitis (eight). Unresponsiveness to medical treatment was observed in 10 and prompted surgical assessment. A partial colectomy was performed in one, and nine underwent a total colectomy (one end stoma and eight ileoanal anastomosis [IAA]). At least one surgical complication occurred in 80% and ultimately six patients with an IAA required an end stoma. Overtime, final diagnosis of 5 out of the 10 surgical patients changed due to biopsy findings, unresponsiveness to medical treatment, or extraintestinal and perianal manifestations. After a 12-year (1-22) follow-up, 57.9% of the diagnoses of all patients were modified. CONCLUSION: EoIBD poses a challenge due to ambiguous presentation and absence of specific diagnostic tests. Surgical evaluation is often needed and surgeons must be mindful of possible initial misdiagnosis, in addition to short- and long-term outcomes before deciding aggressive surgical measures as well as intestinal reconstruction.

Ultrashort Bowel Syndrome Outcome in Children Treated in a Multidisciplinary Intestinal Rehabilitation Unit.

Aim Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in the pediatric population. Our aim was to review long-term outcome of ultrashort bowel syndrome (USBS) in an Intestinal Rehabilitation Unit (IRU). Patients and Methods Retrospective study of patients with USBS (defined as < 10 cm of remnant small bowel) treated between 2000 and 2015. Demographic data, clinical, and treatment variables including parenteral nutrition (PN), surgical techniques, and intestinal transplantation (IT) were analyzed. Results Out of 250 children, 30 referred to the IRU met inclusion criteria. Upon first assessment, patients had a median age of 3 (1-217) months and had undergone 3 (1-6) previous laparotomies that left 5 (0-9) cm of remnant small bowel. The main cause of USBS was neonatal midgut volvulus (50%). Follow-up was 28 (4-175) months. Advanced IF-associated liver disease (IFALD) was documented in 63%. None of the patients achieved digestive autonomy and was consequently considered for IT. One patient was excluded, five died before IT, and three are still on the waiting list. Six patients received an isolated IT, 6 a combined liver IT, and 18 a multivisceral graft. Digestive autonomy was achieved in 71% after 31 (14-715) days after IT and currently 62% are alive and off total PN. A significant drop in IFALD progression prior to IT was observed with the introduction of new lipid emulsions in 2010 (SMOF or Soy oil MCT (mid-chain triglycerides) Olive oil Fish oil). Conclusion A multidisciplinary IRU including an IT program offers a comprehensive approach for patients with IF and is crucial to improve survival rate of USBS. New PN lipid emulsions had an impact on IFALD progression and may eventually reduce overall mortality.

Relationship between patient-reported outcome measures (PROM) and three measures of foot-ankle alignment in patients with metatarsal head pain: a cross-sectional study.

BACKGROUND: The aim of the present study is to establish the relationship between foot-ankle patient-reported outcome measures (PROM) and three measures of foot-ankle alignment (MoFAA) in patients with metatarsal head pain. METHODS: A cross-sectional study where 206 patients completed three PROMs and a clinician recorded three MoFAA bilaterally (three times each). A reliability analysis of the MoFAA, a correlation analysis (between MoFAA and PROM) and regression analysis (dependent variable: PROM; independent variables: MoFAA) were performed. RESULTS: Pearson's coefficient changed in each PROM used, ranging from 0.243 (AAOS-FAMShoeComfortScale-FVARight) to 0.807 (FFIIndex-first MTPJEright). Regression indices (R2-corrected) ranged between 0.117 (AAOS-FAMShoeComfortScale) and 0.701 (FFIIndex). CONCLUSIONS: The MoFAA correlated between moderately to strongly with the foot-ankle PROM selected. The level of correlation between MoFAA and PROM was higher when patients with metatarsal head pain were asked about foot health status, pain and function; however, the correlation was poor when the patient was asked about shoe aspects. In addition, the MoFAA variable that achieved the highest correlation value was the first metatarsophalangeal joint extension. The results obtained in this study could be used in future studies to develop tools for assessing and monitoring patients with metatarsal head pain.

Cross-cultural adaptation and validation of the Spanish version of the American Academy of Orthopaedic Surgeons-Foot and Ankle Module (AAOS-FAMsp).

BACKGROUND: The current study performed a cross-cultural adaptation to Spanish and examined the internal and external validation of the AAOS-FAM questionnaire. METHODS: A direct translation (English to Spanish) and a reverse translation (Spanish to English) were performed by two independent professional native translators. Cronbach's α coefficients were calculated to analyse the internal consistency of the measure. The factor structure and construct validity were analysed after extraction by maximum likelihood (EML); extraction was necessary if the following three requirements were met: accounting for ≥10 % of variance, Eigenvalue >1.0 and a scree plot inflexion point. The standard error of measurement and minimal detectable change 90 (MDC90) were calculated. Criterion validity was calculated by analysing the correlation between the American Academy of Orthopaedic Surgeons-Foot and Ankle Module (Spanish version) (AAOS-FAMsp) and Spanish versions of the questionnaires FFI and FHSQ. RESULTS: Regarding internal consistency, Cronbach's α was 0.877, and in the test-retest analysis, the ICC ranged between 0.899 and 0.942. Error measures were calculated by MDC90 and SEM, which showed values of 3.444 and 1.476 %, respectively. The analysis demonstrated a goodness of fit chi-squared value of 803.166 (p < 0.001). For criterion validity, the correlation value with FFIsp was r = 0.837 (p < 0.01), while the FHSQsp correlation values with different scales ranged from r = 0.206 (p < 0.01) (physical activity) to r = 0.665 (p < 0.01) (pain). CONCLUSIONS: The results indicate that AAOS-FAMsp has satisfactory psychometric properties, facilitating the inclusion of Spanish-speaking individuals into both research and clinical practice.

Surgical Rehabilitation Techniques in Children with Poor Prognosis Short Bowel Syndrome.

Intestinal failure (IF) requires a multidisciplinary management based on nutritional support, surgical and medical rehabilitation, and transplantation. The aim of this study is to review our experience with surgical rehabilitation techniques (SRTs: enteroplasty, Bianchi, Serial Transverse Enteroplasty Procedure [STEP]) in patients with short bowel syndrome (SBS) and poor prognosis due to complex abdominal pathology. We performed a single-center retrospective study of patients with IF evaluated for intestinal transplantation in the Intestinal Rehabilitation Unit who underwent an SRT. Nonparametric tests were used for statistical analysis.A total of 205 patients (107 males/98 females) with mean age of 25 ± 7 months were assessed for IF. A total of 433 laparotomies were performed on 130 patients including intestinal resection, enteroplasties, adhesiolysis, and transit reconstruction. SRT were performed in 22 patients: 12 enteroplasties, 8 STEPs, and 4 Bianchi procedures. All patients were parenteral nutrition (PN) dependent with different stages of liver disease: mild (13), moderate (5), and severe (4). The adaptation rate for patients who underwent enteroplasty, STEP, and Bianchi were 70, 63, and 25%, respectively, although the techniques are not comparable. Overall, intestinal adaptation was achieved in nine (41%) patients, and four (18%) patients showed significant reduction of PN needs. One child did not respond to SRT and did not meet transplantation criteria. The remaining eight (36%) patients were included on the waiting list for transplant: four were transplanted, two are still on the waiting list, and two died. Better outcomes were observed in milder cases of liver disease (mild 77%, moderate 40%, severe 25%) (p < 0.05). Conversely, a trend toward a poorer outcome was observed in cases with ultrashort bowel (p > 0.05). One patient required reoperation after a Bianchi procedure due to intestinal ischemia and six needed further re-STEP or adhesiolysis procedure several months later. The median follow-up was 62 (3-135) months. Overall mortality was 19%, and was due to end-stage liver disease and/or central venous catheter-related sepsis. SRT led to intestinal adaptation in a significant number of patients with poor prognosis SBS referred for intestinal transplantation. However, SRT requires a multidisciplinary evaluation and should be attempted only in suitable cases. Careful assessment and optimal surgical timing is crucial to obtain a favorable outcome.

Trichodysplasia Spinulosa in a 20-Month-Old Girl With a Good Response to Topical Cidofovir 1%.

Trichodysplasia spinulosa (TS) is a rare entity, characterized by a follicular digitate keratosis predominantly affecting the face and variable degrees of hair loss, most severely facial hair, that occurs in immunosuppressed individuals, and is considered to be a viral infection caused by a human polyomavirus, the "TS-associated polyomavirus." Histologically it is characterized by hair follicles with excessive inner root-sheath differentiation and intraepithelial viral inclusions. Correlation of these findings with clinical features is required for diagnosis. Treatment with antiviral agents appears to be the most effective. We report the occurrence of TS in a 20-month-old girl with multivisceral transplantation due to short-bowel syndrome secondary to intestinal atresia and gastroschisis. The patient was treated with cidofovir 1% cream, with significant improvement and without any adverse effects. We describe the youngest patient, to our knowledge, with TS.

Post-transplant lymphoproliferative disorders and other malignancies after pediatric intestinal transplantation: incidence, clinical features and outcome.

PTLDs are a well-recognized and potentially fatal complication after intestinal transplantation. We analyzed the incidence, clinical features, and outcome in a 63 intestinal transplantation series performed in our unit between October 1999 and July 2011. Types of graft included ISB (n = 23), LSB (n = 20), and MV (n = 20). Patients were categorized into three groups of immunosuppression: I (n = 43) received basiliximab, tacrolimus, and steroids; II (n = 11) thymoglobulin and tacrolimus, and III (n = 9) alemtuzumab and tacrolimus. EBV status was serially assessed. All PTLD cases were biopsied to establish histopathological diagnosis. The incidence of PTLD was 14.2% (9/63). Median onset of PTLD after transplant was four months (range: 0.5-28), within first postoperative year in 6 (66.6%) patients. Fever was the most common symptom. Graft removal was needed in four patients (44%). The patient survival rate was 66.6% (6/9). We have not found any association between PTLD and immunosuppression regimen or transplant type. However, there was a statistical association with EBV active infection.

Increasing incidence of pediatric inflammatory bowel disease in Spain (1996-2009): the SPIRIT Registry.

BACKGROUND: Although pediatric inflammatory bowel disease (IBD) diagnosis has increased in the last decades in Spain, there are no consistent epidemiologic data. Our aim was to describe the changing pattern of pediatric IBD incidence in Spain in the last 14 years. METHODS: A retrospective survey of patients diagnosed below 18 years of age in the period 1996-2009 was performed. Patients' data were obtained from the hospitals' databases. To avoid reduced accrual of cases diagnosed by adult physicians, adult IBD units in referral centers were invited to participate. Seventy-eight centers participated in our survey. Rates of incidence were calculated using age-stratified population-based epidemiologic data. Incidence rates were compared for the last 14 years (1996-2009). RESULTS: In total, data from 2107 patients were obtained: 1,165 Crohn's disease (CD, 55.3%), 788 ulcerative colitis (UC, 37.4%), and 154 IBD unclassified. The sex distribution was 56.4% male, with higher predominance for CD (59.3%) as compared to UC (52.8%) and IBD unclassified (53.2%) (P = 0.012). The median age at diagnosis was 12.3 years (p25-75 9.7-14.6) with significant differences between diseases. IBD incidence increased from 0.97 to 2.8/100,000 inhabitants <18 years/year in the study period. Although this increase is more evident for CD (from 0.53 to 1.7), UC has also risen considerably (0.39 to 0.88). CONCLUSIONS: This is the first attempt to calculate the current incidence of pediatric IBD in Spain. A significant increase of incidence rates in the study period was observed. In the last 14 years pediatric IBD incidence has almost tripled, with a more important CD increase.

Characteristics and outcomes of elderly patients refused to ICU.

BACKGROUND: There are few data regarding the process of deciding which elderly patients are refused to ICU admission, their characteristics, and outcome. METHODS: Prospective longitudinal observational cohort study. We included all consecutive patients older than 75 years, who were evaluated for admission to but were refused to treatment in ICU, during 18 months, with 12-month followup. We collected demographic data, ICU admission/refusal reasons, previous functional and cognitive status, comorbidity, severity of illness, and hospital and 12-month mortality. RESULTS: 338 elderly patients were evaluated for ICU admission and 88 were refused to ICU (26%). Patients refused because they were "too ill to benefit" had more comorbidity and worse functional and mental situation than those admitted to ICU; there were no differences in illness severity. Hospital mortality rate of the whole study cohort was 36.3%, higher in patients "too ill to benefit" (55.6% versus 35.8%, P < 0.01), which also have higher 1-year mortality (73.7% versus 42.5%, P < 0.01). High comorbidity, low functional status, unavailable ICU beds, and age were associated with refusal decision on multivariate analysis. CONCLUSIONS: Prior functional status and comorbidity, not only the age or severity of illness, can help us more to make the right decision of admitting or refusing to ICU patients older than 75 years.