Hospital Regional de Concepción

Importance: Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established. Objective: To determine if a peripheral perfusion-targeted resuscitation during early septic shock in adults is more effective than a lactate level-targeted resuscitation for reducing mortality. Design, Setting, and Participants: Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018. Interventions: Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period. Main Outcomes and Measures: The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation-, renal replacement therapy-, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay. Results: Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, -8.5% [95% CI, -18.2% to 1.2%]). Peripheral perfusion-targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, -1.00 [95% CI, -1.97 to -0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed. Conclusions and Relevance: Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT03078712.

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

It has been proposed that the enhanced metabolic activity of tumor cells is accompanied by an increased expression of facilitative hexose transporters (GLUTs). However, a previous immunohistochemical analysis of GLUT1 expression in 154 malignant human neoplasms failed to detect the GLUT1 isoform in 87 tumors. We used 146 normal human tissues and 215 tumor samples to reassess GLUT1 expression. A similar number of samples were used to compare the expression of GLUT2-6 and 9. The classical expression of GLUT1-5 in different normal human tissues was confirmed, however, we were unable to detect GLUT2 in human pancreatic islet cells. GLUT6 was principally detected in testis germinal cells and GLUT9 was localized in kidney, liver, heart, and adrenal. In tumor samples, GLUT1, 2, and 5 were the main transporters detected. GLUT1 was the most widely expressed transporter, however, 42% of the samples had very low-to-negative expression levels. GLUT2 was detected in 31% of the samples, being mainly expressed in breast, colon, and liver carcinoma. GLUT5 was detected in 27% of breast and colon adenocarcinoma, liver carcinoma, lymphomas, and testis seminoma samples. In situ RT-PCR and ultrastructural immunohistochemistry confirmed GLUT5 expression in breast cancer. GLUT6 and 9 are not clearly over-expressed in human cancer. The extensive expression of GLUT2 and 5 (glucose/fructose and fructose transporters, respectively) in malignant human tissues indicates that fructose may be a good energy substrate in tumor cells. Our functional data obtained in vitro in different tumor cells support this hypothesis. Additionally, these results suggest that fructose uptake could be used for positron emission tomography imaging and, may possibly represent a novel target for the development of therapeutic agents in different human cancers.

Most estimates in the literature for the economic cost of treating a diabetic foot ulcer (DFU) are from industrialized countries. There is also marked heterogeneity between the complexity of cases considered in the different studies. The goal of the present article was to estimate treatment costs and costs to patients in five different countries (Chile, China, India, Tanzania, and the United States) for two hypothetical, but well-defined, DFUs at the extreme ends of the complexity spectrum. A co-author, who is a treating physician in the relevant country, was asked to choose treatment plans that represented the typical application of local resources to the DFU. The outcomes were pre-defined as complete healing in case 1 and trans-tibial amputation in case 2, but the time course of treatment was determined by each investigator in a manner that would be typical for their clinic. The costs, in local currencies, for each course of treatment were estimated with the assistance of local hospital administrators. Typical reimbursement scenarios in each country were used to estimate the cost burden to the patient, which was then expressed as a percentage of the annual per capita purchasing power parity-adjusted gross domestic product. There were marked differences in the treatment plans between countries based on the availability of resources and the realities of local conditions. The costs of treatment for case 1 ranged from Int$102 to Int$3959 in Tanzania and in the United States, respectively. The cost for case 2 ranged from Int$3060 to Int$188,645 in Tanzania and in the United States, respectively. The cost burden to the patient varied from the equivalent of 6 days of average income in the United States for case 1 to 5.7 years of average annual income for case 2 in India. Although these findings do not take cost-effectiveness into account, they highlight the dramatic economic burden of a DFU for patients in some countries.

BACKGROUND AND OBJECTIVE: Evidence suggests that synthetic surfactants consisting solely of phospholipids can be improved through the addition of peptides, such as sinapultide, that mimic the action of human surfactant protein-B (SP-B). A synthetic surfactant containing a mimic of SP-B may also reduce the potential risks associated with the use of animal-derived products. Our objective was to compare the efficacy and safety of a novel synthetic surfactant containing a functional SP-B mimic (lucinactant; Discovery Laboratories, Doylestown, PA) with those of a non-protein-containing synthetic surfactant (colfosceril palmitate; GlaxoSmithKline, Brentford, United Kingdom) and a bovine-derived surfactant (beractant; Abbott Laboratories, Abbott Park, IL) in the prevention of neonatal respiratory distress syndrome (RDS) and RDS-related death. METHODS: We assigned randomly (double-masked) 1294 very preterm infants, weighing 600 to 1250 g and of < or =32 weeks gestational age, to receive colfosceril palmitate (n = 509), lucinactant (n = 527), or beractant (n = 258) within 20 to 30 minutes after birth. Primary outcome measures were the rates of RDS at 24 hours and the rates of death related to RDS during the first 14 days after birth. All-cause mortality rates, bronchopulmonary dysplasia (BPD) rates, and rates of other complications of prematurity were prespecified secondary outcomes. Primary outcomes, air leaks, and causes of death were assigned by an independent, masked, adjudication committee with prespecified definitions. The study was monitored by an independent data safety monitoring board. RESULTS: Lucinactant reduced significantly the incidence of RDS at 24 hours, compared with colfosceril (39.1% vs 47.2%; odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.52-0.89). There was no significant difference in comparison with beractant (33.3%). However, lucinactant reduced significantly RDS-related mortality rates by 14 days of life, compared with both colfosceril (4.7% vs 9.4%; OR: 0.43; 95% CI: 0.25-0.73) and beractant (10.5%; OR: 0.35; 95% CI: 0.18-0.66). In addition, BPD at 36 weeks postmenstrual age was significantly less common with lucinactant than with colfosceril (40.2% vs 45.0%; OR: 0.75; 95% CI: 0.56-0.99), and the all-cause mortality rate at 36 weeks postmenstrual age was lower with lucinactant than with beractant (21% vs 26%; OR: 0.67; 95% CI: 0.45-1.00). CONCLUSIONS: Lucinactant is a more effective surfactant preparation than colfosceril palmitate for the prevention of RDS. In addition, lucinactant reduces the incidence of BPD, compared with colfosceril palmitate, and decreases RDS-related mortality rates, compared with beractant. Therefore, we conclude that lucinactant, the first of a new class of surfactants containing a functional protein analog of SP-B, is an effective therapeutic option for preterm infants at risk for RDS.

OBJECTIVES: To examine the independent association between five stages of activities of daily living (ADLs) and mortality after accounting for known diagnostic and sociodemographic risk factors. DESIGN: For five stages of ADLs (0 to IV), determined according to the severity and pattern of ADL limitations, unadjusted life expectancies and adjusted associations with mortality were estimated using a Cox proportional hazards regression model. SETTING: Community. PARTICIPANTS: Nine thousand four hundred forty-seven participants aged 70 and older from the second Longitudinal Study of Aging. MEASUREMENTS: One-, 5-, and 10-year survival and time to death. RESULTS: Median life expectancy was 10.6 years for participants with no ADL limitations and 6.5, 5.1, 3.8, and 1.6 years for those at ADL stages I, II, III, and IV, respectively. The sociodemographic- and diagnostic-adjusted hazard of death at 1 year was five times as great at stage IV as at stage 0 (hazard ratio = 5.6, 95% confidence interval = 3.8-8.3). The associations between ADL stage and mortality declined over time but remained statistically significant at 5 and 10 years. CONCLUSION: ADL stage continued to explain mortality risk after adjusting for known risk factors including advanced age, stroke, and cancer. ADL stages might aid clinical care planning and policy as a powerful prognostic indicator particularly of short-term mortality, improving on current ADL measures by profiling activity limitations of relevance to determining community support needs.

PURPOSE: The aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines. PATIENTS AND METHODS: Forty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records. RESULTS: The overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) beta+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P < .0001). CONCLUSION: Our findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFbeta+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.

AIMS: To review recent data on prevalence and causes of blindness and visual impairment in Latin America. METHOD: Data from recent population-based prevalence surveys in nine countries in Latin America, covering 30,544 people aged 50 years and older, are presented. RESULTS: The prevalence of bilateral blindness (VA <3/60 in the better eye with available correction) ranged from 1.3% in urban Buenos Aires, Argentina, to 4.0% in two rural districts of Peru; low vision from 5.9% in Buenos Aires to 12.5% in rural Guatemala. Cataract was the main cause of blindness (41-87%), followed by posterior segment disease (7-47%). Avoidable blindness ranged from 43% in urban Brazil to 94% in rural Guatemala. CONCLUSIONS: 43% to 88% of all blindness in Latin America is curable, being caused by cataract and refractive errors. Simple and cost-effective intervention strategies exist and need to be made available to more people. Also, the visual outcome from cataract surgery can be improved. In the urban areas with adequate eye care services, blindness and low vision due to posterior segment disease are increasing. Results from these surveys may help planners to estimate the prevalence and causes of blindness in their own area or country.

Background and Aims Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C‐reactive protein (CRP) level as a marker of chronic inflammation. Approach and Results We applied two‐sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR‐Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two‐step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans ( P = 9 × 10 −5 ) and Europeans ( P = 9 × 10 −5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans ( P = 0.03), while higher CRP concentrations increased GBC risk in Europeans ( P = 4.1 × 10 −6 ). European results suggest causal effects of BMI on gallstone disease ( P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. Conclusions Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.

BACKGROUND AND OBJECTIVES: Left ventricular hypertrophy (LVH) is an independent risk factor and an intermediate end point of dialysis-associated cardiovascular comorbidity. We utilized a global pediatric registry to assess the prevalence, incidence, and predictors of LVH as well as its evolution in the longitudinal follow-up in dialyzed children. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cross-sectional echocardiographic, clinical, and biochemical data were evaluated in 507 children on peritoneal dialysis (PD), and longitudinal data were evaluated in 128 patients. The 95(th) percentile of LV mass index relative to height age was used to define LVH. RESULTS: The overall LVH prevalence was 48.1%. In the prospective analysis, the incidence of LVH developing de novo in patients with normal baseline LV mass was 29%, and the incidence of regression from LVH to normal LV mass 40% per year on PD. Transformation to and regression from concentric LV geometry occurred in 36% and 28% of the patients, respectively. Hypertension, high body mass index, use of continuous ambulatory peritoneal dialysis, renal disease other than hypo/dysplasia, and hyperparathyroidism were identified as independent predictors of LVH. The use of renin-angiotensin system (RAS) antagonists and high total fluid output (sum of urine and ultrafiltration) were protective from concentric geometry. The risk of LVH at 1 year was increased by higher systolic BP standard deviation score and reduced in children with renal hypo/dysplasia. CONCLUSIONS: Using height-adjusted left ventricular mass index reference data, LVH is highly prevalent but less common than previously diagnosed in children on PD. Renal hypo/dysplasia is protective from LVH, likely because of lower BP and polyuria. Hypertension, fluid overload, and hyperparathyroidism are modifiable determinants of LVH.

Abstract Rationale The role of and needs for extracorporeal membrane oxygenation (ECMO) at a population level during the coronavirus disease (COVID-19) pandemic have not been completely established. Objectives To identify the cumulative incidence of ECMO use in the first pandemic wave and to describe the Nationwide Chilean cohort of ECMO-supported patients with COVID-19. Methods We conducted a population-based study from March 3 to August 31, 2020, using linked data from national agencies. The cumulative incidence of ECMO use and mortality risk of ECMO-supported patients were calculated and age standardized. In addition, a retrospective cohort analysis was performed. Outcomes were 90-day mortality after ECMO initiation, ECMO-associated complications, and hospital length of stay. Cox regression models were used to explore risk factors for mortality in a time-to-event analysis. Measurements and Main Results Ninety-four patients with COVID-19 were supported with ECMO (0.42 per population of 100,000, 14.89 per 100,000 positive cases, and 1.2% of intubated patients with COVID-19); 85 were included in the cohort analysis, and the median age was 48 (interquartile range [IQR], 41–55) years, 83.5% were men, and 42.4% had obesity. The median number of pre-ECMO intubation days was 4 (IQR, 2–7), the median PaO2/Fi O2 ratio was 86.8 (IQR, 64–99) mm Hg, 91.8% of patients were prone positioned, and 14 patients had refractory respiratory acidosis. Main complications were infections (70.6%), bleeding (38.8%), and thromboembolism (22.4%); 52 patients were discharged home, and 33 died. The hospital length of stay was a median of 50 (IQR, 24–69) days. Lower respiratory system compliance and higher driving pressure before ECMO initiation were associated with increased mortality. A duration of pre-ECMO intubation ≥10 days was not associated with mortality. Conclusions Documenting nationwide ECMO needs may help in planning ECMO provision for future COVID-19 pandemic waves. The 90-day mortality of the Chilean cohort of ECMO-supported patients with COVID-19 (38.8%) is comparable to that of previous reports.

INTRODUCTION: Idiopathic talipes equinovarus is the most common congenital defect characterized by the presence of a congenital dysplasia of all musculoskeletal tissues distal to the knee. For many years, the treatment has been based on extensive surgery after manipulation and cast trial. Owing to poor surgical results, Ponseti developed a new treatment protocol consisting of manipulation with cast and an Achilles tenotomy. The new technique requires 4 years of orthotic management to guarantee good results. The most recent studies have emphasized how difficult it is to comply with the orthotic posttreatment protocol. Poor compliance has been attributed to parent's low educational and low income level. The purpose of the study is to evaluate if poor compliance is due to the complexity of the orthotic use or if it is related to family education, cultural, or income factors. METHOD: Fifty-three patients with 73 idiopathic talipes equinovarus feet were treated with the Ponseti technique and followed for 48 months after completing the cast treatment. There was a male predominance (72%). The mean age at presentation was 1 month (range: 1 wk to 7 mo). Twenty patients (38%) had bilateral involvement, 17 patients (32%) had right side affected, and 16 patients (30%) had the left side involved. The mean time of manipulation and casting treatment was 6 weeks (range: 4 to 10 wk). Thirty-eight patients (72%) required Achilles tenotomy as stipulated by the protocol. Recurrence was considered if there was a deterioration of the Dimeglio severity score requiring remanipulation and casting. RESULTS: Twenty-four out of 73 feet treated by our service showed the evidence of recurrence (33%). Sex, age at presentation, cast treatment duration, unilateral or bilateral, severity score, the necessity of Achilles tenotomy, family educational, or income level did not reveal any significant correlation with the recurrence risk. Noncompliance with the orthotic use showed a significant correlation with the recurrence rate. The noncompliance rate did not show any correlation with the patient demographic data or parent's education level, insurance, or cultural factors as proposed previously. CONCLUSION: The use of the brace is extremely relevant with the Ponseti technique outcome (recurrence) in the treatment of idiopathic talipes equinovarus. Noncompliance is not related to family education, cultural, or income level. The Ponseti postcasting orthotic protocol needs to be reevaluated to a less demanding option to improve outcome and brace compliance.

BACKGROUND: The objective of this study was to determine the impact of sustained virologic response (SVR) to pegylated interferon (peg-IFN) plus ribavirin (RBV) on the incidence of liver-related complications and overall mortality in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS: We included in this prospective cohort study 166 coinfected patients with compensated cirrhosis, who received peg-IFN plus RBV, to assess the time from the starting date of HCV therapy to the first hepatic decompensation and death due to any cause. RESULTS: SVR was observed in 43 (25%) individuals. Two (4.6%) patients with SVR developed liver decompensation vs 33 (26.8%) individuals without SVR (P = .002). The incidence of liver-related complications was 0.89 cases per 100 person-years (95% confidence interval [CI], .11-3.1) in SVR patients and 6.4 cases per 100 person-years (95% CI, 4.5-8.9) in non-SVR patients. Factors independently associated with liver decompensation were non-SVR (hazard ratio [HR], 8.1; 95% CI, 1.08-61.5; P = .042) and MELD score ≥9 at baseline (HR, 2.9; 95% CI, 1.2-7.2; P = .016). Two (4.6%) patients with SVR died due to any cause compared with 22 (17.9%) individuals without SVR (P = .02). MELD score ≥9 (HR, 3.1; 95% CI, 1.3-7.7; P = .011) and non-SVR (HR, 8.0; 95% CI, 1.07-61; P = .043) were independently associated with overall mortality. CONCLUSIONS: The achievement of SVR following peg-IFN plus RBV markedly reduces the incidence of liver-related decompensation and the overall mortality in HIV/HCV-coinfected patients with compensated cirrhosis.

BACKGROUND: Little is known regarding the psychological dysfunction in children who require repetitive surgery for early onset scoliosis (EOS). This study was conducted to examine the neurobehavioral functioning of children with EOS at various stages of treatment with the rib-based growing rod system (RBGRS). We hypothesized that these children would demonstrate evidence of neurobehavioral dysfunction. METHODS: Twelve patients were included in the analyses. At the time of the evaluation, baseline clinical, and demographic information and the number of RBGRS-related surgeries were obtained. All patients were evaluated with semistuctured interviews by a pediatric clinical psychologist using the Behavior Assessment System for Children--2nd Edition-Spanish Version (BASC-2) psychological tool between 1.5 to 3 years from the initial RBGRS implantations. RESULTS: Of the 12 patients under investigation, 25% scored in a clinically significant range on at least 1 scale, 33% scored in an at-risk range on at least 1 scale, and 42% had normal range for all scales in the BASC-2 measurement. Patients who scored in a clinically significant range in at least 1 of the scales in the BASC-2 measurement were younger at initial RBGS implantation. They had more total surgeries and RBGRS surgeries than patients who did not score in the range. CONCLUSIONS: Clinicians caring for children with EOS should have a heightened awareness for possible adverse psychological outcomes in this population and consider early referral for appropriate psychological assessment and care. Additional studies are necessary to further qualify and quantify the psychological effects of multiple anesthesia surgeries in EOS patients. LEVEL OF EVIDENCE: Level III.

BACKGROUND: Mitral valve prolapse (MVP) is a common valve condition and has been associated with sudden cardiac death. Premature ventricular contractions (PVCs) from the papillary muscles (PMs) may play a role as triggers for ventricular fibrillation (VF) in these patients. OBJECTIVES: To characterize the electrophysiological substrate and outcomes of catheter ablation in patients with MVP and PM PVCs. METHODS: Of 597 patients undergoing ablation of ventricular arrhythmias during the period 2012-2015, we identified 25 patients with MVP and PVCs mapped to the PMs (64% female). PVC-triggered VF was the presentation in 4 patients and a fifth patient died suddenly during follow-up. The left ventricle ejection fraction (LVEF) was 50.5% ± 11.8% and PVC burden was 24.4% ± 13.1%. A cardiac magnetic resonance imaging was performed in nine cases and areas of late gadolinium enhancement were found in four of them. A detailed LV voltage map was performed in 11 patients, three of which exhibited bipolar voltage abnormalities. Complete PVC elimination was achieved in 19 (76%) patients and a significant reduction in PVC burden was observed in two (8%). In patients in which the ablation was successful, the PVC burden decreased from 20.4% ± 10.8% to 6.3% ± 9.5% (P = 0.001). In 5/6 patients with depressed LVEF and successful ablation, the LV function improved postablation. No significant differences were identified between patients with and without VF. CONCLUSIONS: PM PVCs are a source of VF in patients with MVP and can induce PVC-mediated cardiomyopathy that reverses after PVC suppression. Catheter ablation is highly successful with more than 80% PVC elimination or burden reduction.

OBJECTIVE: The purpose of this study was to evaluate three ventilator weaning strategies and to evaluate whether the use of continuous positive airway pressure (CPAP) via a nasopharyngeal or endotracheal tube would increase the likelihood of extubation failure in very low birth weight (VLBW) infants. STUDY DESIGN: We studied prospectively 87 preterm infants (mean +/- SD; birth weight: 1078 +/- 188 g; gestational age: 28.8 +/- 2.2 weeks) who were in the process of being weaned from intermittent mandatory ventilation (IMV). Infants were assigned by systematic sampling to one of the following three treatment groups: (1) direct extubation from IMV (D.EXT) (n = 30); (2) preextubation endotracheal CPAP (ET-CPAP) for 12-24 hr (n = 28); or (3) postextubation nasopharyngeal CPAP (NP-CPAP) for 12-24 hr (n = 29). Failure was defined as the need for resumption of mechanical ventilation within 72 hr of extubation due to frequent or severe apnea and/or respiratory failure (pH < 7.25, PaCO2 > 60 mm Hg, and/or requirement for oxygen FiO2 > 60%). RESULTS: There were no significant differences in failure rates among the three procedures. Failures were 2/30 (7%) in D.EXT; 4/28 (14%) in ET-CPAP; and 7/29 (24%) in the NP-CPAP. There were also no differences in FiO2, PaO2, and respiratory rates before and after discontinuation of IMV among the three groups. PaCO2 values were slightly higher in the NP-CPAP group 12-24 hr after weaning from IMV. CONCLUSION: We were unable to demonstrate a clear difference in extubation outcome by use of CPAP administered via an endotracheal or nasopharyngeal tube when compared to direct extubation from low-rate IMV in VLBW infants.

The Vertical Expandable Prosthetic Titanium Rib (VEPTR) is a technique developed for the treatment of progressive early onset scoliosis. This vertically placed device uses distraction to indirectly elongate the spine and chest, stabilizing the progression of the spinal deformity while preserving spinal growth. Thoracic spine and chest wall deformity are usually correlated; therefore, elongation of the chest wall will increase the space available for the lung and improve respiratory mechanics in patients with early onset scoliosis. We conducted a retrospective study of 17 patients with early onset scoliosis treated with the VEPTR technique. The medical records, imaging studies, and follow-up physical examinations were evaluated. The patient population consisted of 17 primary VEPTR implantations and 33 expansion surgeries with a mean follow-up of 25 months. Our results show that there was an improvement in the coronal plane deformity between the presurgical and postsurgical Cobb angles, preoperative Cobb angle of 59 degrees (range 38-77) to postoperative 35 degrees (range 10-70), resulting in an average decrease of 59% in the Cobb angle (P<0.001). The thoracic kyphosis was maintained at anatomically normal values. The surgical technique preserved the space available for the lung. The complication rate was 13%, which includes infection, device migration, and rib fracture. The analysis of the data shows that the natural history of the progressive spinal deformity was improved in all patients. This preliminary report reaffirms that the VEPTR implantation is a safe and efficient method for the treatment of early onset scoliosis.

We studied 28 individuals from a four-generation Chilean family (ADC54) including 13 affected individuals with cataracts, microcornea and/or corneal opacity. All individuals underwent a complete ophthalmologic exam. We screened with a panel of polymorphic DNA markers for known loci that cause autosomal dominant cataracts, if mutated, and refined the locus using the ABI Prism Linkage Mapping Set Version 2.5, and calculated two-point lod scores. Novel PCR primers were designed for the three coding exons, including intron-exon borders, of the candidate gene alpha A crystallin (CRYAA). Clinically, affected individuals had diverse and novel cataracts with variable morphology (anterior polar, cortical, embryonal, fan-shaped, anterior subcapsular). Microcornea and corneal opacity was evident in some. Marker D21S171 gave a lod score of 4.89 (theta(m) = theta(f) = 0). CRYAA had a G414A transition that segregated with the disease and resulted in an amino acid alteration (R116H). The phenotypic variability within this family was significant with novel features of the cataracts and a corneal opacity. With the exception of iris coloboma, the clinical features in all six previously reported families with mutations in the CRYAA gene were found in this family. We identified a novel G414A transition in exon 3 of CRYAA that co-segregated with an autosomal dominant phenotype. The resulting amino acid change R116H is in a highly conserved region and represents a change in charge. The genotype-phenotype correlation of this previously unreported mutation provides evidence that other factors, genetic and/or environmental, may influence the development of cataract as a result of this alteration.

Steroids have been a cornerstone in renal transplant immunosuppression. New immunosuppressive drugs have led to protocols using early steroid withdrawal or complete avoidance. A prospective protocol in 23 pediatric renal transplant (ages 2-14 yr) who received decreasing steroid doses stopping at day 7 post-Tx, FK, and MMF were compared with a CsA, AZT, historically matched steroid-based control group. Basiliximab was used in two doses. Anthropometric, biochemical variables, AR rates, and CMV infection were evaluated and compared using Student's t-test and regression analysis. A better growth pattern was seen in steroid withdrawal group. GFR rate and serum glucose were similar in both groups. Total serum cholesterol levels were significantly lower in steroid withdrawal group. The incidence of AR at 12 months was 4.3% in steroid withdrawal group vs. 8.6% in steroid-based group (p = ns). No difference in CMV infection was observed. Hemoglobin levels were low during the first months in both groups; reached normal values after six months. SBP became higher at 12 months in steroid-based group. Patient and graft survival was 98% in both groups at one-yr post-transplant. Early steroid withdrawal was efficacious, safe, and did not increase risk of rejection, preserving optimal growth, renal function, and reducing cardiovascular risk factors.

The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. Regulatory T cells (Tregs) and Th2 effector cells (Teff) are associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, the main immunomodulatory mechanisms associated with the enrichment of these subsets in OSCC remain unknown. We characterized Th-like lineages in Tregs and Teff and evaluated immunomodulatory changes induced by the TME in OSCC. Our phenotypic data revealed a higher distribution of tumour-infiltrating CCR8 + and Th2-like Treg in OSCC compared with non-malignant samples, whereas the percentages of Th1 cells were reduced in cancer. We then analyzed the direct effect of the TME by exposing T cell subsets to cancer secretomes and observed the OSCC secretome induced CCR8 expression and reduced cytokine production from both subsets. Transcriptomic analysis showed that the co-culture with OSCC secretome induced several gene changes associated with the vitamin D (VitD) signaling pathway in T cells. In addition, proteomic analysis identified the presence of several proteins associated with prostaglandin E2 (PGE2) production by rapid membrane VitD signaling and a reduced presence of the VitD binding protein. Thus, we analyzed the effect of VitD and PGE2 and observed that VitD promotes a regulatory Th2-like response with CCR8 expression whilst PGE2 also modulated CCR8 but inhibited cytokine production in combination with VitD. Finally, we evaluated the presence of CCR8 ligand in OSCC and observed increased chemokine CCL18, which was also able to upregulate CCR8 in activated Th cells. Overall, our data showed the immunomodulatory changes induced by the TME involving CCR8 expression and regulatory Th2 phenotypes, which are associated with PGE2 mediated VitD signaling pathway and CCL18 expression in OSCC.