The Influence of Donor Milk Supplementation on Duration of Parenteral Nutrition in Preterm Infants.

BACKGROUND: Data are limited on the association between the use of donor human milk and improvements in feeding tolerance. OBJECTIVE: To determine the influence of the duration of parenteral nutrition on the growth and morbidity of the breastfed newborn when using donated human milk in the absence of mother's own milk. METHODS: We conducted a retrospective study before and after the intervention that compared two groups of newborns (N = 284; each group n = 142). We used a convenience sample of all newborns ≤32 weeks gestation consecutively admitted in a single unit before (Group 1 between December 2012 and May 2014) or after (Group 2 between October 2014 and December 2016) the availability of donor human milk. In Group 2, donor human milk was administered at least 3 to 4 weeks or until the baby weighed 1,500 g. Weight was recorded daily and length and head circumference weekly. Parenteral nutrition was continued until enteral feeding volume reached 120 ml/kg/day. Additional variables measured were the number of days with a central venous catheter, age that the enteral feeding volume reached 150 ml/kg/day, and duration of stay. RESULTS: The duration of parenteral feeding was the same before and after: 12 (8.23) and 11 (7.19) days (p = .822). The z scores for weight and height of newborns was lower in Group 2 = -1.8 (1.0) and -2.3 (1.1) and Group 1 = -1.2 (1.1) (p < .001) and -1.8 (1.4) (p = .005). CONCLUSION: We did not find an association between the administration of donor human milk as a supplement to mother's own milk and reduced number of days of parenteral nutrition. Back translation by Laurence Grummer-Strawn.

Childhood Neurodevelopmental Outcome in Low Birth Weight Infants With Post-ligation Cardiac Syndrome After Ductus Arteriosus Closure.

BACKGROUND: Post-ligation cardiac syndrome (PLCS) is a common complication of patent ductus arteriosus (PDA) surgical closure in low birth weight infants. It has been associated with mortality, but there is a lack of information about the neurodevelopmental outcome of the survivors. We aimed to explore the prevalence of PLCS and to assess whether this clinical condition is a risk factor for adverse outcome, (moderate or severe neurodevelopmental disabilities). METHODS: We retrospectively reviewed the medical charts of all the infants < 30 weeks of gestation who underwent ductus arteriosus ligation at our unit between 2005 and 2009. RESULTS: During the study period, 39 preterm infants [mean gestational age 26.4 (2) weeks] underwent surgical closure of the PDA at a mean postnatal age of 25.3 (2.3) days. Twenty six percent of the study population developed PLCS. Five infants died and the follow-up was accomplished in 24 infants (70% of the survivors) at a mean age of 5.3 (1.5) years (range 2-9 years). Neurodevelopmental impairment was observed in 6 in the PLCS group (75%) and in 6 infants in the no PLCS group (37%), p = 0.08]. Multiple regression analyses showed that the best fitting model for predicting adverse outcome included PLCS and low birth weight, p = 0.018. CONCLUSION: Preterm infants undergoing surgical closure of PDA who fulfill the criteria of PLCS according to this study seem to have a tendency toward higher risk of long-term neurodevelopmental impairment. Prospective clinical trials reporting long-term follow-up data should be designed to confirm the hypotheses generated in this pilot study.

Validity of Biomarkers of Early Circulatory Impairment to Predict Outcome: A Retrospective Analysis.

Objectives: The definition of circulatory impairment in the premature infant is controversial. Current research suggests overdiagnosis and overtreatment. We aimed to analyse which biomarkers move clinicians to initiate cardiovascular treatment (CVT). The prognostic capacity for adverse outcome (death and/or moderate-severe brain damage by cranial ultrasound at term equivalent) of these biomarkers was evaluated. Study Design: Retrospective data analysis from preterm infants enrolled in a placebo-controlled trial on dobutamine for low superior vena cava (SVC) flow, who showed normal SVC flow within the first 24 h (not randomized). Five positive biomarkers were considered: MABP < gestational age (GA)-1 mmHg; MABP < GA-5 mmHg; lactate > 4 mmol/L; BE < -9 mmol/L; SVC flow <51 ml/kg/min. Results: Ninety eight infants formed the study cohort. Thirty six received CVT (2-95 h). Logistic regression models adjusted for gestational age showed a positive association between CVT and the risk of death or moderate-severe abnormal cranial ultrasound at term equivalent [(OR 5.2, 95%CI: 1.8-15.1) p = 0.002]. MABP < GA-1 mmHg and lactate > 4 mmol/L were the most prevalent biomarkers at start of treatment. Low BE, high serum lactate and low SVC flow at first echocardiography showed a trend toward being associated with adverse outcome, although not statistically significant. Conclusions: Low blood pressure and high lactate are the most prevalent biomarkers used for CVT prescription. Lactic acidosis and low SVC flow early after birth showed a trend toward being associated with adverse outcome. These findings support using a combination of biomarkers for inclusion in a placebo-controlled trial on CVT during transitional circulation.

Egg OIT in clinical practice (SEICAP II): Maintenance patterns and desensitization state after normalizing the diet.

BACKGROUND: It is unknown which are the most suitable maintenance pattern and egg consumption to maintain the desensitization state after ending the oral immunotherapy (OIT). This multicenter, randomized, controlled trial compared two OIT maintenance patterns with pasteurized egg white (PEW), evaluating the egg consumption effect on the desensitization state after ending the OIT. METHODS: One hundred and one children with confirmed egg allergy were randomized: 25 to an egg-free diet (CG) and 76 to an OIT year with PEW and two maintenance patterns, 38 patients to daily 3.3 g proteins (AG) and 38 to every two days (BG). PEW challenge (DBPCFC), adverse reactions, and immune markers were assessed at baseline, at the end of the OIT, and at 6 and 12 months later on ad libitum egg consumption (T0, T12, T18, and T24). A questionnaire evaluated the egg consumption at T18. RESULTS: At T12, 64 of 76 (84.21%) OIT patients had reached total desensitization (32 AG and 32 BG) vs 4 of 25 (16.00%) CG who passed the PEW DBPCFC. Thirty (93.75%) AG vs 25 (78.12%) BG patients completed an OIT year. At T18, 27 of 29 (93.1%) AG vs 20 of 24 (83.3%) BG passed the PEW DBPCFC, 96% consuming at least two egg servings/week. At T24, 97.43% OIT patients passed the challenge. Most patients had adverse reactions, more frequent in the BG patients; frequency and severity of reactions decreased through the study. PEW skin prick test wheal and sIgE antibody serum levels similarly decreased in AG or BG, but AG patients had greater increase in PEW sIgG4 (P < 0.05). CONCLUSIONS: Daily OIT maintenance achieves better adherence, effectiveness, and safety. Two egg servings/week ensure maintained desensitization after the end of an OIT year.

¿Cómo realizamos el cribado de infección tuberculosa latente en pacientes candidatos a terapias biológicas en España? Una encuesta multidisciplinar / Screening for Latent Tuberculosis Infection in Patients who are Candidate for Biological Therapies in Spain? A Multidisciplinary Survey

Introducción: El tratamiento con terapias biológicas aumenta la incidencia de enfermedad tuberculosa. La implementación sistemática del cribado de la infección tuberculosa latente en pacientes que van a recibir estas terapias ha conseguido reducir el riesgo de desarrollarla. En 2016 se publicó en España el Documento de consenso sobre la prevención y el tratamiento de la tuberculosis en pacientes candidatos a tratamiento biológico. El objetivo principal del estudio fue evaluar la adherencia al mismo. Métodos: Estudio multicéntrico, descriptivo, observacional en forma de encuesta anónima online, difundida entre las diferentes sociedades médicas que trabajan con biológicos. Resultados: Se recibieron 747 respuestas. La mayoría de los encuestados realizaba el cribado en el momento adecuado y con la indicación correcta (93,7%). Solo un 36,6% de los encuestados solicitaba las pruebas diagnósticas adecuadas, mientras que el 56,3% acertaron las indicaciones de quimioprofilaxis. Hasta el 96% conocía las pautas de quimioprofilaxis recomendadas, mientras que solo el 63,9% las iniciaba en el momento adecuado. La especialidad con más participación y que más realizaba el cribado de infección tuberculosa latente fue reumatología (54%). En la mayoría de los casos, los neumólogos participaban como consultores. Conclusiones: Este estudio pone de manifiesto un bajo grado de adherencia a las recomendaciones, realizando un cumplimiento aceptable el 56% de los encuestados. Enfatizando en las pruebas diagnósticas adecuadas y en el algoritmo diagnóstico de infección tuberculosa latente, se podría reducir aún más la incidencia de enfermedad tuberculosa en los pacientes que van a recibir terapias biológicas

Introduction: Treatment with biological therapies increases the incidence of tuberculous disease. The introduction of systematic screening for latent tuberculosis infection in patients who are to receive these therapies has reduced this risk. In 2016, the consensus document on the prevention and treatment of tuberculosis in patients who are candidates for biological treatment was published in Spain. The main objective of this study was to evaluate adherence to these guidelines. Methods: Multicenter, descriptive, observational study via an anonymous online survey sent to medical societies involved in biologics. Results: We received 747 responses. Most respondents performed screening at the right time in the right patients (93.7%). Only 36.6% of respondents requested the appropriate diagnostic test, while 56.3% correctly recommended chemoprophylaxis. Up to 96% were familiar with the recommended chemoprophylaxis regimens, while only 63.9% initiated them at the right time. The specialist area that participated most and screened most patients for latent tuberculosis infection was rheumatology (54%). In most cases, pulmonologists were involved in an advisory capacity. Conclusions: This study shows poor overall adherence to recommendations, with only 56% of respondents reporting appropriate compliance. The incidence of tuberculous disease in patients who are to receive biological therapies could be reduced further by emphasizing the importance of the right diagnostic test and use of the diagnostic algorithm for latent tuberculosis infection

Screening for Latent Tuberculosis Infection in Patients who are Candidate for Biological Therapies in Spain? A Multidisciplinary Survey. / ¿Cómo realizamos el cribado de infección tuberculosa latente en pacientes candidatos a terapias biológicas en España? Una encuesta multidisciplinar.

INTRODUCTION: Treatment with biological therapies increases the incidence of tuberculous disease. The introduction of systematic screening for latent tuberculosis infection in patients who are to receive these therapies has reduced this risk. In 2016, the consensus document on the prevention and treatment of tuberculosis in patients who are candidates for biological treatment was published in Spain. The main objective of this study was to evaluate adherence to these guidelines. METHODS: Multicenter, descriptive, observational study via an anonymous online survey sent to medical societies involved in biologics. RESULTS: We received 747 responses. Most respondents performed screening at the right time in the right patients (93.7%). Only 36.6% of respondents requested the appropriate diagnostic test, while 56.3% correctly recommended chemoprophylaxis. Up to 96% were familiar with the recommended chemoprophylaxis regimens, while only 63.9% initiated them at the right time. The specialist area that participated most and screened most patients for latent tuberculosis infection was rheumatology (54%). In most cases, pulmonologists were involved in an advisory capacity. CONCLUSIONS: This study shows poor overall adherence to recommendations, with only 56% of respondents reporting appropriate compliance. The incidence of tuberculous disease in patients who are to receive biological therapies could be reduced further by emphasizing the importance of the right diagnostic test and use of the diagnostic algorithm for latent tuberculosis infection.

La infección por citomegalovirus postrasplante renal y pérdida del injerto a largo plazo / Cytomegalovirus infection after kidney transplantation and long-term graft loss

Antecedentes: A pesar del uso de estrategias de prevención y la mejora en los métodos diagnósticos, el citomegalovirus (CMV) continúa siendo la complicación viral más frecuente después del trasplante renal y su impacto en los resultados a largo plazo se sigue debatiendo. Objetivo: Conocer la incidencia de infección/enfermedad por CMV bajo estrategias de prevención y analizar su asociación con la supervivencia del paciente y del injerto y con otros eventos clínicos relacionados con el CMV. Métodos: Revisión de las historias clínicas de 377 pacientes trasplantados de riñón entre enero de 1998 y diciembre del 2008. Se analizó la supervivencia por el método de Kaplan-Meier en función de la presencia o ausencia de infección/enfermedad CMV y se usó el modelo de Cox para identificar factores asociados con infección/enfermedad por CMV y para evaluar su impacto en la mortalidad y la pérdida del injerto. Resultados: La incidencia de infección por CMV fue del 34,7% y de enfermedad del 9,5%. La supervivencia del paciente y del injerto fue significativamente inferior en los pacientes con infección/enfermedad CMV. La infección/enfermedad por CMV se asoció de forma significativa a mayor riesgo de pérdida del injerto (HR 1,91, IC del 95% 1,09-3,36, p=0,023) pero no con más riesgo de mortalidad (HR 1,29, IC del 95% 0,7-2,38, p=0,4). Conclusión: La replicación viral después del trasplante es un factor de riesgo de pérdida del injerto pero no de mortalidad a largo plazo. Las estrategias de prevención disminuyen la incidencia de infección y enfermedad por CMV postrasplante (AU)

Background: Despite the use of prevention strategies, cytomegalovirus (CMV) infection is the most common viral complication after renal transplant and its impact on long-term outcomes is still open to debate. Objective: To evaluate the incidence of CMV infection and disease during the use of prevention strategies in our centre and to analyse the association between CMV infection and long-term patient and graft survival and other potentially clinical events related with CMV. Methods: We reviewed the medical records of 377 recipients of kidney transplants performed between January 1998 and December 2008. Kaplain-Meier survival curve analysis was performed to analyse graft and patient survival by CMV infection/disease and Cox proportional hazards regression was used to identify factors associated with CMV infection/disease, graft loss and mortality. Results: The incidence of CMV infection was 34.7% and CMV disease was 9.5%. Patient and graft survival was significantly lower in patients with CMV infection/disease. CMV infection/disease was associated with a higher risk of graft loss (HR 1.91, 95% CI 1.09-3.36, p=0.023), but not with a higher mortality (HR 1.29, 95% CI 0.7-2.38, p=0.4). Conclusion: CMV replication after renal transplant is a risk factor for long-term graft loss but not mortality. Prevention strategies decrease post-transplant CMV infection and disease (AU)

Cytomegalovirus infection after kidney transplantation and long-term graft loss. / La infección por citomegalovirus postrasplante renal y pérdida del injerto a largo plazo.

BACKGROUND: Despite the use of prevention strategies, cytomegalovirus (CMV) infection is the most common viral complication after renal transplant and its impact on long-term outcomes is still open to debate. OBJECTIVE: To evaluate the incidence of CMV infection and disease during the use of prevention strategies in our centre and to analyse the association between CMV infection and long-term patient and graft survival and other potentially clinical events related with CMV. METHODS: We reviewed the medical records of 377 recipients of kidney transplants performed between January 1998 and December 2008. Kaplain-Meier survival curve analysis was performed to analyse graft and patient survival by CMV infection/disease and Cox proportional hazards regression was used to identify factors associated with CMV infection/disease, graft loss and mortality. RESULTS: The incidence of CMV infection was 34.7% and CMV disease was 9.5%. Patient and graft survival was significantly lower in patients with CMV infection/disease. CMV infection/disease was associated with a higher risk of graft loss (HR 1.91, 95% CI 1.09-3.36, p=0.023), but not with a higher mortality (HR 1.29, 95% CI 0.7-2.38, p=0.4). CONCLUSION: CMV replication after renal transplant is a risk factor for long-term graft loss but not mortality. Prevention strategies decrease post-transplant CMV infection and disease.

The impact of intrauterine and extrauterine weight gain in premature infants on later body composition.

BackgroundThe impact of intrauterine and extrauterine growth on later insulin resistance and fat mass (FM) in very low birth weight (VLBW) infants is not well established. The aim of our study was to evaluate the effects of intrauterine and early/late extrauterine growth on later insulin resistance and body composition in VLBW infants from 6 months' corrected age (CA) to 36 months.MethodsProspective measurements of body composition by dual-energy X-ray absorptiometry and insulin resistance by homeostasis model assessment insulin resistance (HOMA-IR) along with other fasting plasma biochemistries were made in 95 VLBW infants at 6, 12, 18, and 24 months' CA and 36 months' postnatal age. Mixed-effect models were used to evaluate the effects of age, sex, maturation status, and Δweight SD score on percentage FM (PFM), FM index (FMI), fat-free mass index (FFMI), and HOMA-IR.ResultsPFM and FMI were negatively associated with a decrease in weight-SD scores from birth to 36 weeks' postmenstrual age (PMA; P=0.001) and from 36 weeks' PMA to 6 months' CA (P=0.003). PFM and FMI were higher in AGA than in small for gestational age (SGA) infants. HOMA-IR was not associated with the Δweight-SD scores in either period.ConclusionsCatch-down growth in terms of weight is associated with persistently lower adiposity but not insulin resistance up to 36 months of age.

Sustained low peritoneal effluent CCL18 levels are associated with preservation of peritoneal membrane function in peritoneal dialysis.

Peritoneal membrane failure (PMF) and, ultimately, encapsulating peritoneal sclerosis (EPS) are the most serious peritoneal dialysis (PD) complications. Combining clinical and peritoneal transport data with the measurement of molecular biomarkers, such as the chemokine CCL18, would improve the complex diagnosis and management of PMF. We measured CCL18 levels in 43 patients' effluent and serum at baseline and after 1, 2, and 3 years of PD treatment by retrospective longitudinal study, and evaluated their association with PMF/EPS development and peritoneal risk factors. To confirm the trends observed in the longitudinal study, a cross-sectional study was performed on 61 isolated samples from long-term (more than 3 years) patients treated with PD. We observed that the patients with no membrane dysfunction showed sustained low CCL18 levels in peritoneal effluent over time. An increase in CCL18 levels at any time was predictive of PMF development (final CCL18 increase over baseline, p = .014; and maximum CCL18 increase, p = .039). At year 3 of PD, CCL18 values in effluent under 3.15 ng/ml showed an 89.5% negative predictive value, and higher levels were associated with later PMF (odds ratio 4.3; 95% CI 0.90-20.89; p = .067). Moreover, CCL18 levels in effluent at year 3 of PD were independently associated with a risk of PMF development, adjusted for the classical (water and creatinine) peritoneal transport parameters. These trends were confirmed in a cross-sectional study of 61 long-term patients treated with PD. In conclusion, our study shows the diagnostic capacity of chemokine CCL18 levels in peritoneal effluent to predict PMF and suggests CCL18 as a new marker and mediator of this serious condition as well as a new potential therapeutic target.

Dexamethasone for Parapneumonic Pleural Effusion: A Randomized, Double-Blind, Clinical Trial.

OBJECTIVE: To assess whether dexamethasone (DXM) decreases the time to recovery in patients with parapneumonic pleural effusion. STUDY DESIGN: This was a multicenter, randomized, double blind, parallel-group, placebo-controlled clinical trial of 60 children, ranging in age from 1 month to 14 years, with community-acquired pneumonia (CAP) and pleural effusion. Patients received either intravenous DXM (0.25?mg/kg/dose) or placebo every 6 hours over a period of 48 hours, along with antibiotics. The primary endpoint was the time to recovery in hours, defined objectively. We also evaluated complications and adverse events. RESULTS: Among the 60 randomized patients (mean age, 4.7 years; 58% female), 57 (95%) completed the study. Compared with placebo recipients, the patients receiving DXM had a shorter time to recovery, after adjustment by severity group and stratification by center (hazard ratio, 1.95; 95% CI, 1.10-3.45; P?=?.021). The median time to recovery for patients receiving DXM was 68 hours (2.8 days) shorter than patients receiving placebo (109 hours vs 177 hours; P?=?.037). In exploratory subgroup analysis, the median time to recovery for patients with simple effusion receiving DXM was 76 hours (3.1 days) shorter than for patients with simple effusion receiving placebo (P?=?.017). The median time to recovery for patients with complicated effusion receiving DXM was 14 hours (0.5 days) shorter than for patients with complicated effusion receiving placebo (P?=?.66). The difference in the effect of DXM in the 2 severity groups was not statistically significant (P?=?.138 for interaction). There were no significant differences in complications or adverse events attributable to the study drugs, except for hyperglycemia. CONCLUSION: In this trial, DXM seemed to be a safe and effective adjunctive therapy for parapneumonic pleural effusion. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01261546.

Predicting Full Enteral Feeding in the Postoperative Period in Infants with Congenital Diaphragmatic Hernia.

Introduction The objective of the study is to examine the factors associated with time to achieve full enteral feeding after repair of congenital diaphragmatic hernia. Materials and Methods Demographic, clinical, and therapeutic data were retrospectively assessed, and uni- and multivariate Cox regression were performed to examine factors predictive of achieving full enteral feeding that was defined as time to achieve120 mL/kg/d after surgical repair. Results Of 78 infants, 66 underwent intervention before hospital discharge. All infants who survived had reached full enteral feeding at the time of hospital discharge by a median of 22 days (range: 2-119 days) after surgery and 10 days (range: 1-91) after initiation of postoperative enteral feedings. Independent risk factors associated with a longer time to reach full enteral feeding achievement included gastroesophageal reflux and days of antibiotics in the postoperative period. Daily stool passage preoperatively predicted earlier enteral tolerance. Conclusion Infants who survive congenital diaphragmatic hernia generally are able to achieve full enteral feedings after surgical repair. A longer time to full feeding is needed in the most severe cases, but some specific characteristics can be used to help identify patients at higher risk. Although some of these characteristics are unavoidable, others including rational antibiotic usage and active gastroesophageal reflux prevention and treatment are feasible and may improve enteral tolerance.

The Natural History of Kidney Graft Cortical Microcirculation Determined by Real-Time Contrast-Enhanced Sonography (RT-CES).

BACKGROUND: Kidney transplantation is the therapy of choice for end-stage kidney disease. Graft's life span is shorter than expected due in part to the delayed diagnosis of various complications, specifically those related to silent progression. It is recognized that serum creatinine levels and proteinuria are poor markers of mild kidney lesions, which results in delayed clinical information. There are many investigation looking for early markers of graft damage. Decreasing kidney graft cortical microcirculation has been related to poor prognosis in kidney transplantation. Cortical capillary blood flow (CCBF) can be measured by real-time contrast-enhanced sonography (RT-CES). Our aim was to describe the natural history of CCBF over time under diverse conditions of kidney transplantation, to explore the influence of donor conditions and recipient events, and to determine the capacity of CCBF for predicting renal function in medium term. PATIENTS AND METHODS: RT-CES was performed in 79 consecutive kidney transplant recipients during the first year under regular clinical practice. Cortical capillary blood flow was measured. Clinical variables were analyzed. The influence of CCBF has been determined by univariate and multivariate analysis using mixed regression models based on sequential measurements for each patient over time. We used a first-order autoregression model as the structure of the covariation between measures. The post-hoc comparisons were considered using the Bonferroni correction. RESULTS: The CCBF values varied significantly over the study periods and were significantly lower at 48 h and day 7. Brain-death donor age and CCBF levels showed an inverse relationship (r: -0.62, p<0.001). Living donors showed higher mean CCBF levels than brain-death donors at each point in the study. These significant differences persisted at month 12 (54.5 ± 28.2 vs 33.7 ± 30 dB/sec, living vs brain-death donor, respectively, p = 0.004) despite similar serum creatinine levels (1.5 ± 0.3 and 1.5 ± 0.5 mg/dL). A sole rejection episode was associated with lower overall CCBF values over the first year. CCBF defined better than level of serum creatinine the graft function status at medium-term. CONCLUSION: RT-CES is a non-invasive tool that can quantify and iteratively estimate cortical microcirculation. We have described the natural history of cortical capillary blood flow under regular clinical conditions.

New developments in cerebral blood flow autoregulation analysis in preterm infants: a mechanistic approach.

BACKGROUND: Impaired autoregulation capacity implies that changes in cerebral perfusion follow changes in blood pressure; however, no analytical method has explored such a signal causality relationship in infants. We sought to develop a method to assess cerebral autoregulation from a mechanistic point of view and explored the predictive capacity of the method to classify infants at risk for adverse outcomes. METHODS: The partial directed coherence (PDC) method, which considers synchronicity and directionality of signal dependence across frequencies, was used to analyze the relationship between spontaneous changes in mean arterial pressure (MAP) and the cerebral tissue oxygenation index (TOI). PDCMAP>>TOI indicated that changes in TOI were induced by MAP changes, and PDCTOI>>MAP indicated the opposite. RESULTS: The PDCMAP>>TOI and PDCTOI>>MAP values differed. PDCMAP>>TOI adjusted by gestational age predicted low superior vena cava flow (≤41 ml/kg per min), with an area under the receiver operating characteristic curve of 0.72 (95% CI: 0.63-0.81; P < 0.001), whereas PDCTOI>>MAP did not. The adjusted pPDCMAP>>TOI (the average value per patient) predicted severe intracranial hemorrhage and mortality. CONCLUSION: PDCMAP>>TOI allows for a noninvasive physiological interpretation of the pressure autoregulation process in neonates. PDCMAP>>TOI is a good classifier for infants at risk of brain hypoperfusion and adverse outcomes.

THA revisions using impaction allografting with mesh is durable for medial but not lateral acetabular defects.

BACKGROUND: Most acetabular revisions are managed with cementless hemispherical or elliptical metal implants relying on bone ingrowth. Nonetheless, loss of acetabular bone stock and inability to achieve secure component fixation represent challenges in the setting of revision total hip arthroplasty. Impaction bone grafting (IBG) using allograft represents one option for treatment of this problem. However, cup migration and bone graft resorption are limitations when IBG is used for large segmental defects, and the precise role of IBG as well as the use of mesh (and the kinds of defects for which mesh does not work well) in this setting remains unknown. QUESTIONS/PURPOSES: We therefore evaluated patients undergoing acetabular revision surgery using IBG and a cemented cup in large bone defects to determine (1) the frequency with which the hip center could be restored in hips with Paprosky 3A and 3B defects and in hips with or without the use of metallic mesh during surgery; (2) survivorship of IBG acetabular-revision reconstructions in patients with severe Paprosky 3A and 3B defects; and (3) risk factors for failure of the reconstruction, including the use of mesh and defect severity (3A versus 3B). METHODS: Between 1997 and 2009, we performed 226 acetabular revisions using IBG. During that time, indications for using IBG in this setting included Paprosky 3A and 3B defects without pelvic discontinuity. Of these, 204 (90.2%) were available for followup at a minimum of 5 years (mean, 10 years; range, 5-17 years). There were 100 hips with an intraoperative bone defect of Paprosky 3A and 104 with a 3B. Medial or rim acetabular uncontained defects were treated with medial and/or lateral metallic mesh in 142 hips. We determined the postoperative radiological cup position and acetabular reconstruction of the hip center according to Ranawat in both groups. We assessed the appearance of cup loosening and the possible risk factors with regression analysis. RESULTS: Mean postoperative acetabular abduction angle and vertical, horizontal, and hip rotation center distances improved (p < 0.001 in all parameters). Nine hips showed radiological loosening in the group with bone defect 3A and 16 in Group 3B. The survival rate for loosening at 15 years was 83% (95% confidence interval [CI], 71%-95%) for Group 3A and 73% (95% CI, 60%-84%) for Group 3B (p = 0.04). The survivorship for loosening when using mesh or not at 15 years was: no mesh 89% (95% CI, 74%-99%), medial mesh 85% (95% CI, 72%-97%), lateral mesh 80% (95% CI, 67%-91%), and medial and lateral meshes 54% (95% CI, 31%-76%) (p = 0.008). After controlling the most relevant confounding variables we found that the most important factor associated with loosening was lateral mesh use (p = 0.008; hazard ratio, 2.942; 95% CI, 1.328-6.516). CONCLUSIONS: IBG provides an improvement in reconstruction of the hip rotation center in acetabular revision surgery. Although results are good for contained or medial large defects, hips with a rim or lateral segmental defect may need other options for reconstruction of these challenging surgeries. LEVEL OF EVIDENCE: Level III, therapeutic study.

Randomized, Placebo-Controlled Trial of Dobutamine for Low Superior Vena Cava Flow in Infants.

OBJECTIVE: To gather information for a future confirmatory trial of dobutamine (DB) for circulatory impairment (ie, low superior vena cava [SVC] flow). STUDY DESIGN: A total of 127 infants born at < 31 weeks gestational age were serially scanned from birth to 96 hours after birth. The infants were randomly assigned to 2 groups and were treated with DB (stepwise dose increase, 5-10-15-20 µg/kg/min) or placebo if they had an SVC flow < 41 mL/kg/min within the first 24 hours after birth. The primary outcome measures were the achievement and maintenance of an SVC flow ≥ 41 mL/kg/min. Secondary outcome measures were the short-term evolution of clinical and biochemical variables, near-infrared spectroscopy, cranial Doppler ultrasound, and clinical outcomes. RESULTS: SVC flow increased throughout the first 96 hours for the entire cohort. All of the randomized infants (n = 28) except 2 achieved and maintained an SVC flow ≥ 41 mL/kg/min after intervention; however, the infants treated with DB (n = 16) showed a higher heart rate and improved base excess compared with those treated with placebo (n = 12). Low SVC flow was associated with low gestational age (P = .02) and poor condition at birth (P = .02). Low SVC flow significantly increased the risk of severe ischemic events (OR, 13; 95% CI, 2.4-69.2; P < .01). CONCLUSION: This exploratory trial demonstrates a tendency toward improved short-term clinical and biochemical perfusion variable outcomes in infants with low SVC flow treated with DB. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01605279) and the European Clinical Trials Database (EurodraCT 2009-010901-35).

Maintenance Therapy with 3-monthly Bacillus Calmette-Guérin for 3 Years is Not Superior to Standard Induction Therapy in High-risk Non-muscle-invasive Urothelial Bladder Carcinoma: Final Results of Randomised CUETO Study 98013.

BACKGROUND: Bacillus Calmette-Guérin (BCG) maintenance therapy for 3 yr following BCG induction can reduce the progression of urothelial bladder carcinoma versus BCG induction alone, but is associated with high toxicity. OBJECTIVE: To investigate whether a modified 3-yr BCG maintenance regimen following induction therapy is more effective than standard BCG induction therapy alone and exhibits a low toxicity profile. DESIGN, SETTING, AND PARTICIPANTS: Patients from the outpatient clinics of the participating centres with high-risk non-muscle-invasive bladder carcinoma (NMIBC) were randomised between October 1999 and April 2007. INTERVENTION: Participants received BCG induction once-weekly for 6 wk (no maintenance arm) or BCG induction followed by one BCG instillation every 3 mo for 3 yr (maintenance arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoints were disease-free interval (DFI) and time to progression (TTP). Secondary endpoints included survival duration and toxicity. Differences between treatment arms were tested using Student's t test and χ(2) and log-rank tests. RESULTS AND LIMITATIONS: A total of 397 patients were randomised, 195 to the no-maintenance and 202 to the maintenance arm. A median time to recurrence was not reached in either treatment arm. DFI was similar between the arms (hazard ration [HR] 0.83; 95% CI 0.61-1.13; p=0.2) with disease relapse at 5 yr of 33.5% and 38.5%, respectively. TTP was also similar between the treatment arms (HR 0.79; 95% CI 0.50-1.26; p=0.3), with a progression rate at 5 yr of 16% and 19.5%, respectively. There were no significant differences between the treatment groups for overall survival and cancer-specific survival at 5 yr. Twenty and five patients in the maintenance and no-maintenance arms, respectively, stopped treatment because of toxicity. The most common local side effects were frequency (65% of patients), dysuria (63%), and haematuria (43%); the most frequent systemic side effects were general malaise (7.2%) and fever (34%). CONCLUSIONS: In NMIBC patients treated with maintenance therapy comprising a single BCG instillation every 3 mo for 3 yr following standard induction BCG, we did not observe a decrease in recurrence and progression rates versus induction therapy alone. PATIENT SUMMARY: Patients who undergo surgery to remove bladder cancer are usually treated with bacillus Calmette-Guérin (BCG) for 6 wk if there is a high risk of disease recurrence. Extending BCG therapy by 3 yr can further minimise disease recurrence and progression, but is associated with more side effects. We report that a modified 3-yr BCG treatment regimen showed low toxicity, but seemed to be no more effective than 6-wk treatment. TRIAL REGISTRATION: CUETO 98013.

Clinical, operational and economic outcomes of point-of-care blood gas analysis in COPD patients.

INTRODUCTION: Arterial blood gas analysis is relevant in chronic obstructive pulmonary disease (COPD) management. The aim of this study was to evaluate whether the use of a blood gas analyzer in pulmonology departments improves the clinical, operational and economic outcomes when compared with clinical laboratory measurements. PATIENTS AND METHODS: It is an observational prospective study. 112 patients were selected. After specimen collection, the measurement was performed both in pulmonology office as point-of-care and in laboratory. We evaluated clinical outcomes (modification of the indication of long-term oxygen therapy (LTOT) according to results, changes in blood gas analysis results, relationship of the partial pressure of oxygen (PaO2) obtained in the medical visit and velocity of change of the PaO2, influence of total haemoglobin concentration and the change in PaO2), operational outcomes (turnaround time (TAT) from specimen collection to receiving the blood gas analysis report) and economic outcomes (overall cost per process of patient care). RESULTS: There were discrepancies in the indication of LTOT in 13.4% of patients. All parameters showed changes. PaO2 levels showed changes in 2 ways, though they frequently increase over time. The correlation was not good in the other two clinical outcomes. The median TATs in pulmonology office were 1 min versus 79 in laboratory, with 52 min for specimen preparation and transport and 17 min for TAT intralaboratory. The overall cost for the 112 patients in pulmonology office and laboratory was 16,769.89€ and 22,260.97€ respectively. CONCLUSIONS: The use of a blood gas analyzer in a pulmonology office improves clinical, operational and economic outcomes when compared with clinical laboratory.

Sequential combination of mitomycin C plus bacillus Calmette-Guérin (BCG) is more effective but more toxic than BCG alone in patients with non-muscle-invasive bladder cancer in intermediate- and high-risk patients: final outcome of CUETO 93009, a randomized prospective trial.

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) is an effective therapy in non-muscle-invasive bladder cancer (NMIBC), but it has limitations in terms of recurrence and toxicity. OBJECTIVE: To determine whether the sequential combination of mitomycin C (MMC) and BCG is superior to BCG alone in increasing a disease-free interval (DFI). DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective randomized trial including 407 patients with intermediate- to high-risk NMIBC and allocated 211 to the MMC and BCG arm and 196 to the BCG-alone arm. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The trial was designed to provide concurrently a power of 80% for the detection of a relative risk reduction of 35% (hazard ratio [HR]: 0.65) of disease relapse with a type I error of 0.05. Times to events were estimated using cumulative incidence functions and compared using the Cox regression model. We used the Kaplan-Meier technique to estimate survival curves. RESULTS AND LIMITATIONS: In the intention-to-treat analysis at 5 yr, DFI was significantly improved by the sequential scheme (HR: 0.57; 95% confidence interval [CI], 0.39-0.83; p=0.003), reducing the disease relapse rate from 33.9% to 20.6%. Higher toxicity was observed with the combination, even reducing the MMC dose, especially in G3 local toxicity compared with BCG with a difference of 17.4% (95% CI, 7.6-27.2; p<0.001). In recurrent T1 tumors, the potential benefit of the sequential scheme was more evident than in the remaining subgroup (18.8% vs 12.8%), with a number needed to treat of five versus eight to avoid an event and with similar toxicity. CONCLUSIONS: Although the sequential scheme is more effective than BCG alone in reducing disease relapse, due to higher toxicity it could be offered only to patients with a high likelihood of recurrence, such as those with recurrent T1 tumors. PATIENT SUMMARY: We analyzed the outcomes of a randomized trial demonstrating that in intermediate- to high-risk non-muscle-invasive bladder cancer, mitomycin C and bacillus Calmette-Guérin (BCG) reduced disease relapse compared with BCG alone but was more toxic. Consequently, it could be offered only to patients with recurrent T1 tumors. TRIAL REGISTRATION: CUETO 93009.