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.

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.

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.

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.

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).

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.

The evolution of the technique of impaction bone grafting in femoral revision surgery has improved clinical outcome. A prospective mid-term study.

Ninety-three patients (97 hips) underwent impaction bone grafting (IBG) using a cemented tapered femoral stem at our institution. Forty-one hips were operated between 1993 and 1998 (group 1) and 56 hips between 1999 and 2007 (group 2). The use of an extended trochanteric osteotomy and a long stem was more frequent in group 2. Group 2 hips showed a better clinical result. One hip was revised for aseptic loosening and most failures were early periprosthetic fractures. The survival rate for reoperation for any cause was 82.9% for group 1 and 84.3% for group 2. Patients in group 1 had a higher risk for periprosthetic fractures and radiological subsidence >5mm. Experience and the evolution of the IBG technique have improved the good long-term outcome.

High prevalence of occult hepatitis C virus infection in patients with primary and secondary glomerular nephropathies.

The association of hepatitis C virus (HCV) infection and glomerulonephritis is well known. However, the relationship between immune-mediated glomerulonephritis and occult HCV, characterized by the presence of HCV-RNA in liver or in peripheral blood mononuclear cells in the absence of serological markers, is unknown. We tested this in 113 anti-HCV-negative patients; 87 with immune-mediated glomerulonephritis and 26 controls with hereditary glomerular nephropathies. All patients were serum HCV-RNA negative by conventional real-time PCR. Significantly, occult HCV-RNA (detectable viral RNA in peripheral blood mononuclear cells or in serum after ultracentrifugation) was found in 34 of 87 patients with immune-mediated glomerulonephritis versus 1 of 26 control patients. The serum creatinine levels were significantly higher in patients with immune-mediated glomerulonephritis with than in those without occult HCV (1.5 versus 1.1 mg/dl, respectively). A multivariate analysis adjusted for gender showed a significantly increased risk of occult HCV in patients with immune-mediated glomerulonephritis versus the controls (odds ratio of 13.29). Progression to end-stage renal disease tended to be faster in patients with immune-mediated glomerulonephritis and occult HCV than in the negative cases. Thus, occult HCV is strongly associated with immune-mediated glomerulonephritis and may have a role in the progression of the disease.

New time-frequency method for cerebral autoregulation in newborns: predictive capacity for clinical outcomes.

OBJECTIVE: To describe an alternative analysis in the frequency-domain of the temporal relationship between 2 biological signals and evaluate the method's predictive capacity for classifying infants at risk for an adverse outcome. STUDY DESIGN: We studied 54 infants (mean gestational age 27 weeks) with invasive mean arterial blood pressure monitoring. The bivariate autoregressive spectral coherence (BiAR-COH) method and the spectral coherence methods were used to analyze the relationship between spontaneous changes in mean arterial blood pressure and the near-infrared tissue oxygenation index. RESULTS: The mean postnatal age at the beginning and end of the autoregulation study was 6.0 (3.0) and 29.0 (7.5) hours, respectively. The BiAR-COH was superior to the spectral coherence in predicting low superior vena cava (SVC) flow (≤ 41 mL/kg per minute), with an area under the receiver operating characteristic curve of 0.84 (95% CI, 0.77-0.90; P < .001). The BiAR-COH threshold for identifying low SVC flow was 0.577, with 0.8 sensitivity and 0.76 specificity. After adjusting for the repeated measures effect (multiple epochs) in a given patient, the averaged BiAR-COH per patient and averaged COH per patient were calculated as the average value per patient. The pBiAR-COH (but not the pCOH) was associated with intraventricular hemorrhage grades 3 and 4 and predicted mortality. CONCLUSIONS: The BiAR-COH classifier identifies low SVC flow infants who are at risk for brain hypoperfusion. The BiAR-COH is superior to frequency domain methods in predicting adverse outcomes in infants.

Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery.

BACKGROUND: Inodilators are routinely used in cardiovascular surgery with cardiopulmonary bypass (CPB). Information regarding safety and tolerability of the novel molecule, levosimendan (LEVO), in newborns is anecdotal; no pharmacokinetic data in this population are available. METHODS: This was a phase I, randomized, and blinded study. Neonates undergoing surgical repair for congenital heart defects received stepwise dose increases of milrinone (MR; 0.5-1 µg/kg/min, n = 9) or LEVO (0.1-0.2 µg/kg/min, n = 11) as an i.v. continuous infusion, starting before CPB. Infants had continuous, time-locked, physiological, and near-infrared spectroscopy (NIRS) (cerebral and peripheral) recordings during the first 24 h, and at 48 and 96 h postsurgery. Serial biochemistry and pharmacokinetic studies were performed. RESULTS: During the first 24 h postsurgery, patients showed time-related, group-independent increased cerebral tissue oxygenation and decreased diastolic blood pressure; in addition, group-dependent differences in heart rate and peripheral perfusion were found. Early postsurgery, MR-treated infants showed lower pH, higher glycemia, and higher inotrope score. The groups differed in cerebral NIRS-derived variables from 24 to 96 h. Study drug withdrawal at 96 h was more frequent with LEVO. LEVO intermediate metabolites were detected in plasma at day 14 after surgery. CONCLUSION: LEVO is well tolerated in critically ill neonates. LEVO may have advantages over MR in terms of the dosing regimen.

Increase of cortical bone after a cementless long stem in periprosthetic fractures.

BACKGROUND: Healing and functional recovery have been reported using an extensively porous-coated stem in Vancouver B2 and B3 periprosthetic fractures; however, loss of cortical bone has been observed when using these stems in revision surgery for aseptic loosening. However, it is unclear whether this bone loss influences subsequent loosening. QUESTION/PURPOSES: We analyze the healing fracture rate and whether the radiographic changes observed around and extensively porous-coated stem used for periprosthetic fractures affect function or loosening. METHODS: We retrospectively reviewed 35 patients with periprosthetic fractures (20 Vancouver B2 and 15 Vancouver B3). Patients' mean age at surgery was 80 years (range, 51-86 years). No cortical struts were used in this series. We evaluated radiographs for signs of loosening or subsidence. The cortical index and the femoral cortical width were measured at different levels on the immediate pre- and postoperative radiographs and at different periods of followup. The minimum followup was 3 years (mean, 8.3 years; range, 3-17 years). RESULTS: All fractures had healed, and all stems were clinically and radiographically stable at the end of followup. Nineteen hips showed nonprogressive radiographic subsidence during the first 3 postoperative months without clinical consequences. The cortical index and the lateral and medial cortical thickness increased over time. Increase of femoral cortex thicknesses was greater in cases with moderate preoperative osteoporosis and in cases with stems less than 16 mm in thickness. CONCLUSIONS: Our data suggest an extensively porous-coated stem for Vancouver B2 and B3 periprosthetic fractures leads to a high rate of union and stable fixation. Cortical index and lateral cortex thickness increased in these patients with periprosthetic fractures. Patients with moderate osteoporosis and those using thin stems showed a major increase in femoral cortex thickness over time.

Reconstruction of the rotation center of the hip after oblong cups in revision total hip arthroplasty.

BACKGROUND: The preoperative bone defect and the reconstruction of the center of rotation of the hip are critical in acetabular revision surgery. Uncemented oblong cups are employed in order to manage these issues. We analyzed the clinical results and rates of revision of two different uncemented oblong cups, the reconstruction of the center of rotation of the hip, as well as the rate of radiological loosening and possible risk factors. MATERIALS AND METHODS: Forty-five patients (46 hips) underwent acetabular revision surgery using two different uncemented oblong cups. We assessed the clinical results and the survival rate for revision and aseptic loosening. Intraoperative bone loss was classified according to Paprosky, and acetabular reconstruction was assessed according to Ranawat. The mean follow-up was 7.2 years (range 4-11 years). RESULTS: There were four re-revisions (three due to aseptic loosening); the survival rate for re-revision due to aseptic loosening was 60.1 % at seven years. The mean distance between the center of the femoral head prosthesis and the approximate center of the femoral head improved from 21.5 to 10.2 mm. Thirteen cups showed radiological loosening; the survival rate for radiological loosening at seven years was 40.54 %. A smaller postoperative horizontal distance was correlated with cup loosening. CONCLUSIONS: Although optimal acetabular reconstruction can be achieved by using oblong uncemented cups in revision hip surgery, the clinical and radiological results are not encouraging. Excessive medialization of the cup may increase the rate of loosening.

Perinatal morbidity and risk of hypoxic-ischemic encephalopathy associated with intrapartum sentinel events.

OBJECTIVE: To examine perinatal morbidity and rate of hypoxic-ischemic encephalopathy in infants exposed to intrapartum sentinel events. STUDY DESIGN: Retrospective cohort study from 2000-2005. Perinatal mortality, perinatal morbidity and rate of hypoxic-ischemic encephalopathy were compared in 3 groups of infants exposed to different risk factors for perinatal asphyxia (sentinel events, nonreassuring fetal status, elective cesarean section). RESULTS: Five hundred eighty-six infants were studied. Perinatal mortality was 6% in the sentinel event group and 0.3% in the nonreassuring fetal status group (relative risk, 2.4; 95% confidence interval, 1.95-2.94). Perinatal morbidity was 2-6 times more frequent in infants exposed to sentinel events; the incidence of hypoxic-ischemic encephalopathy was 10%, compared with 2.5% in the nonreassuring fetal status group (relative risk, 1.93; 95% confidence interval, 1.49-2.52). No infant in the elective cesarean section group died, had perinatal morbidity, or developed encephalopathy. CONCLUSION: Intrapartum sentinel events are associated with a high incidence of perinatal morbidity and hypoxic-ischemic encephalopathy.

An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer.

BACKGROUND: Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse. METHODS: We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models. RESULTS: An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database. CONCLUSIONS: This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples.

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.

Predicting nonmuscle invasive bladder cancer recurrence and progression in patients treated with bacillus Calmette-Guerin: the CUETO scoring model.

PURPOSE: Bacillus Calmette-Guerin is the most effective therapy for nonmuscle invasive bladder cancer. Recently to calculate the risks of recurrence and progression based on data from 7 European Organisation for Research and Treatment of Cancer trials a scoring system was reported. However, in that series only 171 patients were treated with bacillus Calmette-Guerin. We developed a risk stratification model to provide accurate estimates of recurrence and progression probability after bacillus Calmette-Guerin. MATERIALS AND METHODS: Data were analyzed on 1,062 patients treated with bacillus Calmette-Guerin and included in 4 Spanish Urological Club for Oncological Treatment trials. Stepwise multivariate Cox models were used to determine the effect of prognostic factors. In each patient the weight of all factors was summed to a total score. Patients were then divided into groups, and cumulative recurrence and progression rates were calculated. RESULTS: A scoring system was calculated with a score of 0 to 16 for recurrence and 0 to 14 for progression. Patients were categorized into 4 groups by score, and recurrence and progression probabilities were calculated in each group. For recurrence the variables were gender, age, grade, tumor status, multiplicity and associated Tis. For progression the variables were age, grade, tumor status, T category, multiplicity and associated Tis. For recurrence calculated risks using Spanish Urological Club for Oncological Treatment tables were lower than those obtained with Sylvester tables. For progression probabilities were lower in our model only in patients with high risk tumors. CONCLUSIONS: We propose a scoring model to stratify the risk of recurrence and progression in patients treated with bacillus Calmette-Guerin.

Baseline cortisol levels, total proteins, and eosinophil count as predictors of hemodynamic response to steroid treatment in septic shock.

BACKGROUND: Our aim was to study if baseline serum cortisol is related to the hemodynamic response to steroid treatment in septic shock patients and if the measurement of total proteins and eosinophil count improves its accuracy. METHODS: A retrospective analysis was performed in 66 consecutive surgical septic shock patients receiving steroid treatment. Four criteria were chosen to define hemodynamic improvement based on the combination of noradrenaline (NA) withdrawal (at 24 and 48 hour) and an increase of the hemodynamic index (HI = mean arterial pressure/NA dose) of 150% at 24 hour and of 350% at 48 hour. The accuracy of the serum cortisol to predict the hemodynamic response to steroid treatment following the four criteria was determined by receiver operating characteristic curve analysis. RESULTS: The largest area under curve was found for the NA withdrawal or an increase of the hemodynamic index >350% at 48 hour after starting the steroid treatment (area under curve, 0.686; 95% CI, 0.553-0.819; p = 0.01). This criteria was met by 35 patients (53%) and was associated with a lower mortality (25.7% vs. 67.7%, p = 0.001). However, no clear serum cortisol cutoff value for the diagnosis of adrenal insufficiency based on the hemodynamic response could be found. Neither the baseline proteins nor the eosinophils improved the accuracy of cortisol to predict hemodynamic improvement. CONCLUSION: The measurement of serum cortisol in surgical septic shock patients does not accurately predict the hemodynamic response to steroids. No clear cutoff value for cortisol, alone or in combination with total protein and/or eosinophil count, can be defined to indicate steroid treatment.

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.