James W. Schroeder

Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study

BACKGROUND Patients with systemic lupus erythematosus (SLE) who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide, represent a subset of patients at high risk of early death. We investigated the safety and efficacy of immune suppression and autologous haemopoietic stem-cell infusion to treat such patients. METHODS From 1996, we selected patients with persistent SLE despite use of cyclophosphamide. Patients underwent dose-intense immune suppression and autologous haemopoietic stem-cell (CD34) infusion. Peripheral blood lymphocytes were analysed by flow cytometry, ELISA, and T-cell-receptor spectratyping before and after transplantation. We mobilised autologous haemopoietic stem cells with 2.0 g/m2 cyclophosphamide and 10 microg/kg granulocyte colony stimulating factor daily, enriched with CD34-positive selection, and reinfused after immunosuppression with 200 mg/kg cyclophosphamide, 1 g methylprednisolone, and 90 mg/kg equine antithymocyte globulin. RESULTS Nine patients underwent stem-cell mobilisation but two were excluded before transplantation because of infection. The remaining seven received high-dose chemotherapy and stem-cell infusion. Median time to an absolute neutrophil count higher than 0.5x10(9)/L and nontransfused platelet count higher than 20x10(9)/L was 9 days (range 8-11) and 11 days (10-13), respectively. At a median follow-up of 25 months (12-40), all patients were free from signs of active lupus. Renal, cardiac, pulmonary, and serological markers, and T cell phenotype and repertoire had normalised. INTERPRETATION Patients remained free from active lupus and improved continuously after transplantation, with no immunosuppressive medication or small residual doses of prednisone. T-cell repertoire diversity and responsiveness was restored. Durability of remission remains to be established.

Synchronous Airway Lesions and Outcomes in Infants With Severe Laryngomalacia Requiring Supraglottoplasty

BACKGROUND Beta-Carotene has been reported to produce regressions in patients with oral leukoplakia, a premalignant lesion. However, previous studies have all been of short duration, with clinical response as the end point. OBJECTIVE To evaluate the duration of response and the need for maintenance therapy in subjects who respond to beta-carotene. METHODS In this multicenter, double-blind, placebo-controlled trial, subjects were given beta-carotene, 60 mg/d, for 6 months. At 6 months, responders were randomized to continue beta-carotene or placebo therapy for 12 additional months. RESULTS Fifty-four subjects were enrolled in the trial, with 50 being evaluable. At 6 months, 26 subjects (52%) had a clinical response. Twenty-three of the 26 responders completed the second, randomized phase. Only 2 (18%) of 11 in the beta-carotene arm and 2 (17%) of 12 in the placebo arm relapsed. Baseline biopsies were performed in all patients, with dysplasia being present in 19 (38%) of the 50 evaluable patients. A second biopsy was obtained at 6 months in 23 subjects who consented to this procedure. There was improvement of at least 1 grade of dysplasia in 9 (39%), with no change in 14 (61%). Nutritional intake was assessed using food frequency questionnaires. There was no change in carotenoid intake during the trial. Responders had a lower intake of dietary fiber, fruits, folate, and vitamin E supplements than did nonresponders. Beta-carotene levels were measured in plasma and oral cavity cells. Marked increases occurred during the 6-month induction. However, baseline levels were not restored in subjects taking placebo for 6 to 9 months after discontinuation of beta-carotene therapy. CONCLUSIONS The activity of beta-carotene in patients with oral leukoplakia was confirmed. The responses produced were durable for 1 year.

Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: a retrospective analysis

BACKGROUND Autologous haemopoietic stem-cell transplantation (HSCT) benefits patients with systemic sclerosis but has been associated with significant treatment-related mortality and failure to improve diffusion capacity of carbon monoxide (DLCO). We aimed to assess efficacy of HSCT and use of rigorous cardiac screening in this group. METHODS We assessed patients with diffuse systemic sclerosis or limited systemic sclerosis and interstitial lung disease who were treated with HSCT as part of a study or on a compassionate basis at Northwestern University (Chicago, IL, USA) or the University of São Paulo (Ribeirão Preto, Brazil). Unselected peripheral blood stem cells were harvested with cyclophosphamide (2 g/m(2)) and filgrastim. The transplant regimen was a non-myeloablative regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (rATG; 4·5-6·5 mg/kg). We followed patients up to 5 years for overall survival, relapse-free survival, modified Rodnan skin score, and pulmonary function tests. FINDINGS Five (6%) of 90 patients died from treatment-related causes. Despite standard guidelines that recommend echocardiogram for screening before transplantation, four treatment-related deaths occurred because of cardiovascular complications (one constrictive pericarditis, two right heart failures without underlying infection, and one heart failure during mobilisation), and one death was secondary to sepsis without documented underlying heart disease. Kaplan-Meier analysis showed survival was 78% at 5 years (after eight relapse-related deaths) and relapse-free survival was 70% at 5 years. Compared with baseline, we noted improvements after HSCT in modified Rodnan skin scores at 1 year (58 patients; p<0·0001), 2 years (42 patients; p<0·0001), and 3 years (27 patients; p<0·0001) and forced vital capacity at 1 year (58 patients; p=0·009), 2 years (40 patients; p=0·02), and 3 years (28 patients; p=0·004), but total lung capacity and DLCO were not improved significantly after HSCT. Overall mean DLCO was significantly improved in patients with normal baseline echocardiograms (p=0·005) or electrocardiographs (p=0·05). INTERPRETATION Autologous HSCT with a non-myeloablative regimen of cyclophosphamide and rATG with a non-selected autograft results in sustained improvement in skin thickness and forced vital capacity. DLCO is affected by baseline cardiac function. Guidelines for cardiac screening of patients with systemic sclerosis to assess treatment-related risk from pulmonary artery hypertension, primary cardiac involvement, or pericardial disease should be reconsidered and updated. FUNDING None.

Branchial anomalies in the pediatric population

OBJECTIVE: We sought to review the presentation, evaluation, and treatment of branchial anomalies in the pediatric population and to relate these findings to recurrences and complications. STUDY DESIGN AND SETTING: We conducted a retrospective study at a tertiary care pediatric hospital. PATIENTS: Ninety-seven pediatric patients who were treated for branchial anomalies over a 10-year period were reviewed. Patients were studied if they underwent surgical treatment for the branchial anomaly and had 1 year of postoperative follow-up; 67 children met criteria, and 74 anomalies were studied. RESULTS: Patients with cysts presented at a later age than did those with branchial anomaly fistulas or sinus branchial anomalies. 32% of branchial anomalies were previously infected. Of these, 71% had more than one preoperative infection. 18% of the BA were first arch derivatives, 69% were second arch derivatives and 7% were third arch derivatives. There were 22 branchial cysts, 31 branchial sinusies and 16 branchial fistulas. The preoperative and postoperative diagnoses differed in 17 cases. None of the excised specimens that contained a cystic lining recurred; all five recurrences had multiple preoperative infections. CONCLUSIONS: Recurrence rates are increased when there are multiple preoperative infections and when there is no epithelial lining identified in the specimen.

Supraglottoplasty outcomes in relation to age and comorbid conditions

OBJECTIVE To determine if age and comorbid conditions effect outcomes in children undergoing supraglottoplasty for severe laryngomalacia. DESIGN Retrospective study. SETTING Urban tertiary-care childrens hospital. PATIENTS Children undergoing supraglottoplasty for severe laryngomalacia between February 2004 and July 2008. 56 patients were identified. OUTCOME MEASURES Persistence of upper airway obstruction, revision surgery (supraglottoplasty), and additional surgery (tracheostomy). RESULTS 33/56 (58.9%) patients had no comorbid conditions and 23/56 (41.1%) patients had comorbid conditions. In noncomorbid patients, 36.4% of those less than 2 months of age at the time of surgery required revision supraglottoplasty, compared to 5.3% of patients between 2 and 10 months (p<0.05). Compared to the 2-10-month age group, there was a significantly higher percentage of patients with comorbid conditions in the >10-month group (32.1% vs. 79%, p<0.01). Patients with comorbid conditions were diagnosed at a significantly later age than those without (6 mo vs. 2 mo, respectively), and had significantly higher rates of revision supraglottoplasty (47.8% vs. 18.2%) and tracheostomy (39.1% vs. 0.0%). 70% of children with neurological conditions required revision surgery, with 60% requiring tracheostomy. The revision surgery and tracheostomy rates were significantly higher compared to the noncomorbid group (p<0.01 and p<0.0001). Children with cardiac conditions had a higher rate of tracheostomy than noncomorbid children (30% vs. 0%, p<0.01). 16.7% of children with genetic conditions required supraglottoplasty, and none required tracheostomy. CONCLUSIONS In noncomorbid patients, those undergoing supraglottoplasty less than 2 months of age had a significantly higher rate of revision supraglottoplasty. Patients with neurologic and cardiac comorbidities require tracheostomy at a significantly higher rate than noncomorbid patients.

Assessment of adenoid size: A comparison of lateral radiographic measurements, radiologist assessment, and nasal endoscopy

OBJECTIVES Correlate adenoid size as determined by lateral neck radiographs and intra-operative mirror exam. Determine if a radiologists assessment of the lateral neck X-ray correlates with adenoid size. Assess the correlation of endoscopic findings to the degree of adenoid hypertrophy seen on intra-operative mirror exam. To perform a cost analysis of radiographic and endoscopic evaluations of the adenoids. STUDY DESIGN Retrospective study. METHODS Patients who underwent adenoidectomy were reviewed. The adenoid size as determined by the adenoid-to-nasopharyngeal (A/N) ratio, radiology report, and flexible nasal endoscopy were compared to the adenoid size as determined by intra-operative mirror nasopharyngeal exam. Compensation rates for each modality were compared. RESULTS Sixty-one children had pre-operative airway radiography. Ninety-nine patients underwent flexible nasopharyngoscopy. When the A/N ratio was compared to the intra-operative mirror exam, the Pearson Correlation coefficient was 0.64 (p<0.0001). The radiology reading was compared to intra-operative mirror exam and the Spearman Correlation coefficient was 0.29 (p=0.0258). When endoscopic nasopharyngoscopy was compared to intra-operative mirror exam, the Pearson Correlation coefficient was 0.62 (p<0.0001). The cost of nasal endoscopy was

Tracheal cartilaginous sleeve in patients with craniosynostosis syndromes: a meta-analysis

654. Lateral airway radiography plus radiology interpretation cost

Congenital Laryngeal Stenosis

605. CONCLUSION Children who undergo lateral radiographs to assess adenoid size are younger than those who undergo awake flexible endoscopic nasopharyngoscopy. Both the A/N ratio and endoscopic nasopharyngoscopy correlate well with the findings of the intra-operative mirror exam. The radiologist interpretations that do not utilize the A/N ratio measurement do not correlate well with intra-operative mirror exam findings. Both modalities are comparable in cost.

Aberrant EGFR and Chromosome 7 Associate with Outcome in Laryngeal Cancer

OBJECTIVES The purpose of this study is to determine if there is a survival advantage to having a tracheostomy in patients with tracheal cartilaginous sleeve (TCS), to determine if the age of the patient at the time of tracheostomy affects morbidity, and to determine if patients with a true pars membranacea have a survival advantage and less morbidity than those without a pars membranacea. STUDY DESIGN Case report and meta-analysis of the literature were conducted. METHODS A review of the world literature from 1979 to 2006 was performed. All reports of patients with craniofacial syndromes found to have TCS by autopsy or endoscopic findings were included. A case report of a new patient with TCS is presented. RESULTS Patients who undergo tracheostomy have a statistically significant survival advantage (P = .0067). The patients age at the time of tracheostomy was not associated with survival time (P = .45). There is no association with absence or presence of a pars membranacea and clinical symptoms of respiratory distress (P = .50). There is no overall difference in survival between patients with a pars membranacea and those without (P = .78). CONCLUSION Tracheostomy placement in patients with TCS and craniosynostosis can decrease morbidity and increase survival. Interval bronchoscopy is important to treat tracheal stoma granulation tissue. There is no survival advantage to having TCS with a pars membranacea.

Pediatric Obstructive Sleep Apnea Syndrome

Congenital subglottic stenosis is rare and as a consequence may not be considered in children experiencing respiratory difficulty at birth. Diagnosis after a child already is intubated complicates the recognition and blurs the boundary between congenital and acquired lesions. This article discusses the anatomy of the larynx, its common anatomic variations, and its response to trauma, a thorough understanding of which is required for the accurate diagnosis and treatment of this complicated problem. The authors discuss evaluation and assessment options to guide treatment.