What spelling errors can tell us about the development of processes involved in children's spelling.

Introduction: Spelling is an essential foundation for reading and writing. However, many children leave school with spelling difficulties. By understanding the processes children use when they spell, we can intervene with appropriate instruction tailored to their needs. Methods: Our study aimed to identify key processes (lexical-semantic and phonological) by using a spelling assessment that distinguishes different printed letter strings/word types (regular and irregular words, and pseudowords). Misspellings in the test from 641 pupils in Reception Year to Year 6 were scored using alternatives to binary correct versus incorrect scoring systems. The measures looked at phonological plausibility, phoneme representations and letter distance. These have been used successfully in the past but not with a spelling test that distinguishes irregularly spelled words from regular words and pseudowords. Results: The findings suggest that children in primary school rely on both lexical-semantic and phonological processes to spell all types of letter string, but this varies depending on the level of spelling experience (younger Foundation/Key stage 1 and older Key stage 2). Although children in younger year groups seemed to rely more on phonics, based on the strongest correlation coefficients for all word types, with further spelling experience, lexical processes seemed to be more evident, depending on the type of word examined. Discussion: The findings have implications for the way we teach and assess spelling and could prove to be valuable for educators.

Comparison of Anticoagulation Strategies in Patients Requiring Venovenous Extracorporeal Membrane Oxygenation: Heparin Versus Bivalirudin.

OBJECTIVES: Extracorporeal membrane oxygenation is a life-sustaining therapy for severe respiratory failure. Extracorporeal membrane oxygenation circuits require systemic anticoagulation that creates a delicate balance between circuit-related thrombosis and bleeding-related complications. Although unfractionated heparin is most widely used anticoagulant, alternative agents such as bivalirudin have been used. We sought to compare extracorporeal membrane oxygenation circuit thrombosis and bleeding-related outcomes in respiratory failure patients receiving either unfractionated heparin or bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation support. DESIGN: Retrospective cohort study. SETTING: Single-center, cardiothoracic ICU. PATIENTS: Consecutive patients requiring venovenous extracorporeal membrane oxygenation who were maintained on anticoagulation between 2013 and 2020. INTERNVENTIONS: IV bivalirudin or IV unfractionated heparin. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were the presence of extracorporeal membrane oxygenation in-circuit-related thrombotic complications and volume of blood products administered during extracorporeal membrane oxygenation duration. One hundred sixty-two patients receiving unfractionated heparin were compared with 133 patients receiving bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation. In patients receiving bivalirudin, there was an overall decrease in the number of extracorporeal membrane oxygenation circuit thrombotic complications (p < 0.005) and a significant increase in time to circuit thrombosis (p = 0.007). Multivariable Cox regression found that heparin was associated with a significant increase in risk of clots (Exp[B] = 2.31, p = 0.001). Patients who received bivalirudin received significantly less volume of packed RBCs, fresh frozen plasma, and platelet transfusion (p < 0.001 for each). There was a significant decrease in the number major bleeding events in patients receiving bivalirudin, 40.7% versus 11.7%, p < 0.001. CONCLUSIONS: Patients receiving bivalirudin for systemic anticoagulation on venovenous extracorporeal membrane oxygenation experienced a decrease in the number of extracorporeal membrane oxygenation circuit-related thrombotic events as well as a significant decrease in volume of blood products administered.

Head and Neck Microsurgeon Practice Patterns and Perceptions Regarding Venous Thromboembolism Prophylaxis.

BACKGROUND: Patients undergoing head and neck (H&N) microvascular reconstruction comprise a population at high risk for venous thromboembolism (VTE). Free flap and VTE thromboprophylaxis may coincide but tend to vary from surgeon to surgeon. This study identifies VTE prophylaxis patterns and perceptions among H&N microsurgeons in the United States. METHODS: An online survey on VTE prophylaxis practice patterns and perceptions was emailed to 172 H&N microsurgeons in the United States using an anonymous link. RESULTS: There were 74 respondents (43% response rate). These surgeons completed residencies in otolaryngology (59%), plastic surgery (31%), and oral maxillofacial surgery (7%). Most underwent fellowship training (95%) and have practiced at an academic center (97%) for at least 6 years (58%), performing an average of 42 ± 31 H&N free flap cases per year (range = 1-190). Most adhered to general VTE prophylaxis guidelines (69%) while 11% did not and 20% were unsure. Nearly all surgeons (99%) would provide prophylactic anticoagulation, mostly in the form of subcutaneous heparin (51%) or enoxaparin (44%); 64% additionally used aspirin, while 4% used aspirin alone. The majority of surgeons (68%) reported having postoperative VTE complications, with six surgeons (8%) reporting patient deaths due to pulmonary embolism. A third of the surgeons have encountered VTE prophylaxis-related adverse bleeding events, but most still believe that chemoprophylaxis is important for VTE prevention (92%). While 35% of surgeons were satisfied with their current practice, most would find it helpful to have official prophylactic anticoagulation guidelines specific to H&N free flap cases. CONCLUSION: The majority of microsurgeons experienced postoperative VTE complications after H&N free flap reconstruction despite the routine use of prophylactic anticoagulation. Though bleeding events are a concern, most surgeons believe chemoprophylaxis is important for VTE prevention and would welcome official guidelines specific to this high-risk population.

Intervention for a lexical reading and spelling difficulty in two Greek-speaking primary age children.

An intervention study was carried out with two nine-year-old Greek-speaking dyslexic children. Both children were slow in reading single words and text and had difficulty in spelling irregularly spelled words. One child was also poor in non-word reading. Intervention focused on spelling in a whole-word training using a flashcard technique that had previously been found to be effective with English-speaking children. Post-intervention assessments conducted immediately at the end of the intervention, one month later and then five months later showed a significant improvement in spelling of treated words that was sustained over time. In addition, both children showed generalisation of improvement to untrained words and an increase in scores in a standardised spelling assessment. The findings support the effectiveness of theoretically based targeted intervention for literacy difficulties.

Influence of fiber connectivity in simulations of cardiac biomechanics.

PURPOSE: Personalized computational simulations of the heart could open up new improved approaches to diagnosis and surgery assistance systems. While it is fully recognized that myocardial fiber orientation is central for the construction of realistic computational models of cardiac electromechanics, the role of its overall architecture and connectivity remains unclear. Morphological studies show that the distribution of cardiac muscular fibers at the basal ring connects epicardium and endocardium. However, computational models simplify their distribution and disregard the basal loop. This work explores the influence in computational simulations of fiber distribution at different short-axis cuts. METHODS: We have used a highly parallelized computational solver to test different fiber models of ventricular muscular connectivity. We have considered two rule-based mathematical models and an own-designed method preserving basal connectivity as observed in experimental data. Simulated cardiac functional scores (rotation, torsion and longitudinal shortening) were compared to experimental healthy ranges using generalized models (rotation) and Mahalanobis distances (shortening, torsion). RESULTS: The probability of rotation was significantly lower for ruled-based models [95% CI (0.13, 0.20)] in comparison with experimental data [95% CI (0.23, 0.31)]. The Mahalanobis distance for experimental data was in the edge of the region enclosing 99% of the healthy population. CONCLUSIONS: Cardiac electromechanical simulations of the heart with fibers extracted from experimental data produce functional scores closer to healthy ranges than rule-based models disregarding architecture connectivity.

HelexKids: A word frequency database for Greek and Cypriot primary school children.

In this article, we introduce HelexKids, an online written-word database for Greek-speaking children in primary education (Grades 1 to 6). The database is organized on a grade-by-grade basis, and on a cumulative basis by combining Grade 1 with Grades 2 to 6. It provides values for Zipf, frequency per million, dispersion, estimated word frequency per million, standard word frequency, contextual diversity, orthographic Levenshtein distance, and lemma frequency. These values are derived from 116 textbooks used in primary education in Greece and Cyprus, producing a total of 68,692 different word types. HelexKids was developed to assist researchers in studying language development, educators in selecting age-appropriate items for teaching, as well as writers and authors of educational books for Greek/Cypriot children. The database is open access and can be searched online at www.helexkids.org .

A sublexical training study for spelling in a biliterate Greek- and English-speaking child.

RI is an emergent trilingual boy, literate in Greek and English, with difficulties in reading and spelling in both languages. Assessment with non-literacy tests revealed a deficit in phonological ability and in visual memory for sequentially presented characters. RI took part in a training programme that targeted sublexical spelling processes. Post-intervention assessment revealed improvement in reading and spelling in Greek but not in English. Assessments of lexical and sublexical skills showed improvement in nonword spelling and nonword reading for Greek. For English, there was some indication of improvement in nonword reading at delayed post-intervention testing, but no evidence of improvement in nonword spelling. Possible reasons for the difference in outcome for the two languages are considered, including the level of transparency of written Greek and English.

Tadalafil therapy for sarcoidosis-associated pulmonary hypertension.

Sarcoidosis-associated pulmonary hypertension (SAPH) is estimated to occur in at least 5% or more of sarcoidosis patients, and it contributes to significant morbidity and mortality. Optimal therapy for SAPH is not well established. We performed a 24-week open-label trial of tadalafil for SAPH at 2 academic medical centers. Subjects were required to have confirmed sarcoidosis plus a right heart catheterization within 12 months of enrollment showing a mean pulmonary artery pressure ≥ 25 mmHg, a pulmonary artery wedge pressure ≤ 15 mmHg, and a calculated pulmonary vascular resistance ≥ 3 Wood units. Subjects received 20 mg/day of tadalafil for the first 4 weeks and then 40 mg/day for the subsequent 20 weeks. Sixteen patients were screened, 12 of whom met criteria for enrollment. At 24 weeks, there was no overall improvement in 6-minute walk distance (6MWD). Five of the 12 subjects dropped out of the study early (2 for social reasons, 3 for medical reasons). There was no significant change in short form 36, St. George's respiratory questionnaire, or maximum Borg dyspnea scores over the 24 weeks. There were no significant adverse events or laboratory abnormalities clearly related to tadalafil in the cohort. The study did not meet the primary end point of change in 6MWD because of the small sample size. Tadalafil was generally safely administered in this cohort of SAPH patients. There was a relatively high dropout rate but no major adverse events and no clinical worsening. Larger studies are needed to explore this question further. (Trial registration: ClinicalTrials.gov identifier: NCT01324999).

Impacto del cambio de técnica de biopsia en tasa de detección de cáncer prostático: estudio prospectivo en 456 pacientes / Impact of changes in biopsy technique in detection rate of prostate cancer: a prospective study in 456 patients

El propósito de este estudio es comparar dos métodos para realizar una biopsia de próstata en dos grupos similares de pacientes. En el grupo A se hicieron 8-12 cores y en el grupo B de 13 a 18 cores. Pacientes y método: Un estudio prospectivo fue planeado para comparar los resultados de la biopsia de próstata realizado por los mismos dos operadores, y por el mismo patólogo (HV) en 456 biopsias consecutivas divididas en dos grupos comparables de pacientes a lo largo de cuatro años, con las mismas indicaciones para la biopsia .Resultados: Desde enero 2005 hasta junio 2009 456 biopsias se realizaron en la Conac V región. En el grupo A se obtuvo una tasa de detección del cáncer de 24,8 por ciento, por el otro lado en el Grupo B 38,1 por ciento, lo que fue estadísticamente significativo con p = 0,003. La detección de cáncer en general para toda la serie, fue 34,77 por ciento. Las complicaciones fueron mayores en el grupo B con 4 casos de sepsis que requirieron hospitalización en comparación con 1 caso en el grupo A, no hubo mortalidad en la serie. Conclusiones: En este trabajo dos grupos de pacientes comparables con indicaciones idénticas sometidos a biopsia de próstata, diferentes sólo en el número de pinchazos –cores obtenidos. El grupo donde se obtuvieron 13 a 18 muestras tuvo un porcentaje significativamente mayor de cáncer de próstata, pero con aumento de las complicaciones. Recomendamos que no perder la oportunidad de llegar a por lo menos 13 muestras en pacientes con sospecha de cáncer de próstata.

The purpose of this study is to compare two methods for prostate biopsy in two similar groups of patients. PATIENTS AND METHOD A prospective study was planned to compare the results of the prostate biopsy performed by the same two operators and by the same pathologist (HV) in 456 consecutive biopsies divided in two comparable groups of patients over the course of four years with the same indications for biopsy . In group A 8-12 cores were made and in group B 13 to 18 cores. RESULTS: From January 2005 to June 2009 456 biopsies were performed at Conac V region. In group A a cancer detection rate of 24.8 percent was obtained, on the other side in Group B 38.1 percent, which was statistically significant with p = 0.003.Overall cancer detection for the entire series, was 34.77 percent . Complications were higher in group B with 4 cases of sepsis that required hospitalization versus 1 case in group A, there was no mortality in the series. CONCLUSIONS: In this work two groups of comparable patients with identical indications underwent prostate biopsy, different only in the number of punctures –cores obtained. The Group where 13-18 samples were obtained had a significantly higher percentage of prostate cancers but with increased complications. We recommend not to miss the opportunity to get to at least 13 samples from patients with suspected prostate cancer.

Ambrisentan for sarcoidosis associated pulmonary hypertension.

BACKGROUND: Sarcoidosis associated pulmonary hypertension (SAPH) is associated with significant morbidity and mortality. There is a paucity of information concerning therapy for this condition. METHODS: We performed a prospective, open-label, proof of concept trial of ambrisentan for SAPH. 21 subjects with SAPH received 5 mg/day of ambrisentan for 4 weeks and then 10/mg day for 20 subsequent weeks. RESULTS: No significant change was noted in the 6-minute walk distance over the course of the study (mean change between week 0 and 24: 9.8 +/- 54.6 meters, p: NS). There were also no significant differences between weeks 0 and 24 in terms of dyspnea as measured by the modified Borg scale, serum brain naturetic peptide, diffusing capacity, and quality of life as measured by the Short Form-36. There was a high dropout rate: overall: 11/21, 52%; social reasons: 3/21, 14%; medical reasons: 8/21, 38% because of dyspnea: 6/21, 29% and/or edema: 4/21, 19%. Of those who completed the 24 week study (10/21, 48%), there was an improvement in their WHO functional class and a marked improvement in their health related quality of life as measured by the St. George Respiratory questionnaire (-15.3 +/- 25.0). However both these improvments did not reach statistical significance possibly because of the small sample size. CONCLUSION: Although ambrisentan was not well tolerated by many of these subjects with SAPH, in those who remained in this 24-week trial, improvements in WHO functional class and in health related quality of life suggested a possible benefit of this drug in selected patients.

Non-tuberculous mycobacteria in end stage cystic fibrosis: implications for lung transplantation.

BACKGROUND: WC and NS contributed equally. Non-tuberculous mycobacteria (NTM) frequently colonise patients with end stage cystic fibrosis (CF), but its impact on the course of the disease following lung transplantation is unknown. METHODS: Lung transplant recipients with CF who underwent lung transplantation at our institution between January 1990 and May 2003 (n=146) and CF patients awaiting lung transplantation in May 2003 (n=31) were studied retrospectively. RESULTS: The prevalence rate of NTM isolated from respiratory cultures in patients with end stage CF referred for lung transplantation was 19.7%, compared with a prevalence rate of 13.7% for NTM isolates in CF lung transplant recipients. The overall prevalence of invasive NTM disease after lung transplantation was low (3.4%) and was predicted most strongly by pre-transplant NTM isolation (p=0.001, Fisher's exact test, odds ratio (OR) 6.13, 95% CI 3.2 to 11.4). This association was restricted to Mycobacterium abscessus (p = 0.005, Fisher's exact test, OR 7.45, 95% CI 2.9 to 16.9). While NTM disease caused significant morbidity in a small number of patients after transplantation, it was successfully treated and did not influence the post-transplant course of the disease. CONCLUSION: The isolation of NTM before transplantation in CF patients should not be an exclusion criterion for lung transplantation, but it may alert the clinician to patients at risk of recurrence following transplantation.

Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial.

Everolimus is a proliferation signal inhibitor with immunosuppressive activity that may reduce the rate of progression of chronic rejection, bronchiolitis obliterans syndrome (BOS), after lung transplantation. In a randomized, double-blind clinical trial, 213 BOS-free maintenance patients received everolimus (3 mg/day) or azathioprine (AZA, 1-3 mg/kg/day) in combination with cyclosporine and corticosteroids. The prospectively defined primary endpoint was the incidence of efficacy failure (decline in FEV1 >15%[deltaFEV1 >15%], graft loss, death or loss to follow-up) at 12 months. Incidence of efficacy failure at 12 months was significantly lower in the everolimus group than AZA (21.8% vs. 33.9%; p = 0.046); at 24 months, rates of efficacy failure became similar between the groups. At 12 months, the everolimus group had significantly reduced incidences of deltaFEV1 >15%, deltaFEV1 >15% with BOS, and acute rejection. At 24 months, only incidence of acute rejection remained significantly less in the everolimus group. Treatment discontinuations (particularly due to adverse events), serious adverse events and high serum creatinine values were more common with everolimus. For the first time, a drug has demonstrated significant slowing of loss in lung function, suggesting that patients kept on prolonged maintenance treatment with everolimus may benefit from replacing AZA with everolimus 3 months after lung transplantation.

Bilateral hematogenous Pseudomonas aeruginosa endophthalmitis after lung transplantation.

Pseudomonas aeruginosa commonly colonizes the airways of patients with cystic fibrosis (CF). However, the occurrence of bacteremia with metastatic infection to the eye causing endogenous endophthalmitis is very rare. In the setting of lung transplantation, the significance of P. aeruginosa bacteremia in patients with CF whose airways are colonized before transplantation is unknown. We report a case of bilateral P. aeruginosa endogenous endophthalmitis in a patient with CF after lung transplant without documented bacteremia. The patient presented with acute eye symptoms in the presence of a left atrial thrombus and the disease followed a rapidly progressive course requiring aggressive medical-surgical treatment. Typically P. aeruginosa endophthalmitis has been associated with a poor visual prognosis. However, with combined medical-surgical management this patient retained useful vision in one eye without having retinal detachment or requiring enucleation. Endogenous endophthalmitis should be considered in the differential diagnosis of ocular complaints in patients with CF after lung transplant.

Combined donor specific transfusion and anti-CD154 therapy achieves airway allograft tolerance.

BACKGROUND: The state of tolerance allows long term graft survival without immunosuppressants. Lung transplantation tolerance has not been consistently achieved in either small or large animal models. METHODS: The mechanisms and effectiveness of a tolerance induction protocol consisting of donor specific transfusion (DST; day 0) and a short course of co-stimulatory blockade (anti-CD154 antibody; days -7, -4, 0 and +4) were studied in the mouse heterotopic tracheal transplant model of chronic lung rejection. C57BL/6 mice received BALB/c tracheal grafts (day 0) and were treated with DST alone, anti-CD154 alone, the combination (DST/anti-CD154), or no treatment. No non-specific immunosuppressants were used. RESULTS: DST/anti-CD154 in combination, but neither treatment alone, markedly prolonged the lumen patency and survival (>100 days) of fully histo-incompatible allografts (p<0.05 versus control allografts at every time point studied up to 16 weeks) without immunosuppression. This protocol was donor antigen specific as third party grafts (C3H) were promptly rejected. In addition, DST/anti-CD154 did not result in mixed chimerism but induced transplantation tolerance via a peripheral mechanism(s), which included significantly reduced cytotoxic T cell activity (p<0.001) and a significantly increased percentage of CD4+CD25+ cells (p = 0.03). CONCLUSIONS: The DST/anti-CD154 protocol successfully induced and maintained long term, donor specific tolerance in the mouse heterotopic airway graft model of chronic lung rejection. This finding may lead us closer to successful tolerance induction in lung transplantation.

Artritis intermitentes y periódicas / Intermittent and periodic arthritis

Los compromisos articulares intermitentes y periódicos son numerosos y algunos de ellos, frecuentes en la práctica habitual. Se manifiestan clínicamente como artralgias predominantemente traumáticas, mecánicas o posturales; artrosis de naturaleza degenerativas, metabólicas o mecánicas o artritis de carácter inflamatorio. Entre éstas últimas las hay febriles; de causa sistémica o local y de naturaleza inmunológica o idiopática. Las més frecuentes son las artritis por cristales (gota y condrocalcinosis) y las artritis reactivas (síndrome de Reiter, artritis enteropáticas, espondiloartritis anquilosante, artritis psoriática). Entre los cuadros infrecuentes están la hidroartrosis intermitente, el reumatismo palindrómico y algunos síndromes febriles periódicos hereditarios como la fiebre mediterránea familiar. En general estos cuadros no comprometen el estado general del paciente; son autolimitados y no dejan secuelas, pero plantean problemas de diagnóstico diferencial.

Short-term calcitriol administration improves calcium homeostasis in adults with cystic fibrosis.

Osteoporosis is a well-defined health risk in cystic fibrosis (CF) patients due to many factors. Vitamin D insufficiency, despite routine cholecalciferol supplementation in CF patients, may contribute to a relative secondary hyperparathyroidism and possibly deficient bone mineralization. An alternate form of vitamin D, calcitriol, was studied to determine short-term effects on fractional calcium absorption and other calciotropic markers in 10 adult CF subjects and in 10 age-, sex- and body mass index (BMI)-matched controls. Serum fractional absorption of (45)Ca was determined after a calcium-containing meal prior to calcitriol intervention. Other measurements included serum parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and urinary calcium:creatinine and N-telopeptide (NTx) concentrations. Both groups were then given calcitriol (0.5 micro g p.o. b.i.d. for 14 days) and restudied following the same protocol. Both groups increased their fractional absorption of (45)Ca after calcitriol ( p=0.015 CF subjects, p=0.001 controls), although calcitriol tended to be less effective in the CF group compared with the controls ( p=0.055). Post-prandial serum PTH concentrations were suppressed compared with baseline in both groups ( p=0.03 CF subjects, p=0.006 controls). Urinary NTx concentrations, a marker for bone resorption, decreased significantly in CF subjects after calcitriol (96.0+/-16.0 vs 63.9+/-12.7 nmol BCE/mmol Cr, p=0.01) and remained unchanged in the control group. The controls had an increase in serum 1,25(OH)(2)D concentrations (69.9+/-4.2 vs 90.7+/-9.6 pmol/l, p=0.02) while there was no significant change in the CF group. Oral calcitriol administration appears to improve markers of calcium balance in adults with CF by increasing fractional absorption of (45)Ca and lowering PTH concentrations, similar to its known effects in healthy subjects, while also suppressing urinary NTx, a marker of bone turnover.

Artritis reumatoídea / Rheumatoid arthritis

La artritis reumatoídea es una enfermedad inflamatoria crónica y sistémica del mesénquima, caracterizada por compromisos articulares simétricos y extraarticulares, de etiología desconocida y de patogenia multifactorial en la que destacan un terreno genético y alteraciones autoinmunes, (celulares y humorales), con producción de citoquinas y autoanticuerpos(factor reumatoídeo) que conducen a los procesos destructivos articulares a través del pannus y a los compromisos extrarticulares. Prácticamente, todas las articulaciones diartrodiales se pueden comprometer, destacando la "mano reumatoidea" deformante y con grados variables de discapacidad. En el compromiso extraarticular destaca el nódulo reumatoídeo y la vasculitis reumatoídea. El 80 por ciento de los pacientes tiene factor reumatoídeo positivo en el suero (serositivo), el que a títulos altos indica mayor agresividad de la enfermedad. Las alteraciones articulares radiológicas tienen un alto grado de especificidad diagnóstica al igual que la biopsia sinovial. El estudio del líquido sinovial puede ser de utilidad en el diagnóstico diferencial con artrosis o con procesos infecciosos crónicos. La velocidad de sedimentación de 100 mm en la 1§ hora o más indica enfermedad grave con compromiso vascular. El tratamiento de la artritis reumatoidea requiere de un equipo múltiplidisciplinario coordinado por el reumatólogo. El médico general o de atención primaria debe estar capacitado para sospechar o diagnosticar artritis reumatoídea e iniciar tratamiento sintomático del dolor e inflamación y derivar a la brevedad al paciente al reumatólogo para completar el tratamiento con drogas de acción lenta o modificadoras del curso de la enfermedad y/o con terapia biológica

Long term results of lung transplantation for cystic fibrosis.

OBJECTIVES: We reviewed our experience with lung transplant for cystic fibrosis (CF) over a 10-year period to identify factors influencing long-term survival. METHODS: One hundred and twenty-three patients with CF have undergone 131 lung transplant procedures at our institution; 114 have had bilateral sequential lung transplants (DLTX) and nine have had bilateral lower lobe transplants from living donors. Three patients had retransplant for acute graft failure, and five had late retransplant for bronchiolitis obliterans syndrome (BOS). Kaplan-Meier survival was calculated for the entire cohort and for subsets at higher risk of death to determine factors predicting a better outcome. RESULTS: Actuarial survival for the entire group of DLTX CF patients was 81% at 1 year, 59% at 5 years, and 38% at 10 years. Lobar transplant was associated with a poorer survival (37.5% at 1 and 5 years). Among DLTX patients, colonization with Burkholderia cepacia was present in 22 patients and was associated with poorer outcome (1- and 5-year survival 60 and 36% in B. cepacia patients vs. 86 and 64% in non-cepacia patients). DLTX patients younger than age 20 (n=22) had a similar survival to patients age 20 or older (n=90). Being on a ventilator at the time of transplant was not associated with poorer survival (n=8). BOS affects increasing numbers of survivors with time. Five CF patients have been retransplanted due to BOS with one operative death and 1-year survival of 60%. CONCLUSIONS: DLTX has acceptable long term survival in CF adults and children with end stage disease. CF patients colonized with B. cepacia have a worse outcome but transplantation is still warranted.

Abnormal bone turnover in cystic fibrosis adults.

Cystic fibrosis (CF) patients often have low bone mineral density (BMD) and may suffer from fractures and kyphosis. The pathogenesis of low BMD in CF is multifactorial. To study bone metabolism, we collected fasting serum and urine from 50 clinically stable CF adults (mean age 28 years) and 53 matched controls to measure markers of bone formation and bone resorption. The CF subjects had moderate lung disease (FEV1: 46.1 +/- 18.6% predicted) and malnutrition (BMI: 20.0 +/- 3.3 kg/m2). Only 3 subjects had normal BMD. CF subjects had higher urinary N-telopeptides of type I collagen (81.0 +/- 60.0 vs 49.0 +/- 24.2 nm BCE/mmol creatinine, p = 0.0006) and free deoxypyridinoline (7.3 +/- 5.0 vs 5.3 +/- 1.9 nM/mM, p = 0.004) levels than controls. Serum osteocalcin levels were similar in the two groups, a result confirmed by two immunoassays that recognize different epitopes on osteocalcin. Serum bone-specific alkaline phosphatase levels were elevated in CF patients (32.0 +/- 11.3 vs 21.8 +/- 7.0 U/l, p < 0.0001), but were much more closely associated with serum total alkaline phosphatase levels (r = 0.51, p = 0.001) than with age or gender. Parathyroid hormone levels were elevated (p = 0.007) and 25-hydroxyvitamin D levels were depressed (p = 0.0002) in the CF patients in comparison with controls. These results indicate that adults with CF have increased bone resorption with little change in bone formation. Medications that decrease bone resorption or improve calcium homeostasis may be effective therapies for CF bone disease.