Partial cricotracheal resection for severe pediatric subglottic stenosis: update of the Lausanne experience.

Until recently, severe pediatric subglottic stenosis (SGS) has been treated almost exclusively by laryngotracheoplasty procedures. Even in the most experienced centers, the results of single-stage operations for Cotton's grade III and IV stenoses have been disappointing. This paper reports our experience on 31 partial cricotracheal resections for severe SGS in infants and children. The stenosis was congenital in 6 cases and acquired after prolonged intubation in 25 cases. Twenty-seven patients were tracheotomy-dependent at the time of surgery. Twenty-two cases were classified as grade III and 9 cases as grade IV stenoses according to Cotton. The decannulation rate was 97% (30 of 31 cases) after an open procedure. There were no fatalities and no lesions to the recurrent laryngeal nerves, but there was 1 complete restenosis. Twenty-seven patients show no exertional dyspnea, 3 have a slight stridor with some dyspnea while exercising, and 1 patient is not decannulated. The voice is normal in 21 cases, a dysphonia is present in 9 cases, and the patient with complete restenosis acquired an esophageal voice. Postoperative follow-up is longer than 10 years in 8 cases and longer than 5 years in an additional 6 cases. All patients who reached adulthood show normal growth of the larynx and trachea. Considering the excellent results obtained in this consecutive series of 31 cases, partial cricoid resection with primary thyrotracheal anastomosis should be considered an important treatment option for severe SGS in infants and children.

Cerebrospinal fluid PCR analysis and biochemistry in bodies with severe decomposition.

The aim of this study was to assess whether Neisseria meningitidis, Listeria monocytogenes, Streptococcus pneumoniae and Haemophilus influenzae can be identified using the polymerase chain reaction technique in the cerebrospinal fluid of severely decomposed bodies with known, noninfectious causes of death or whether postmortem changes can lead to false positive results and thus erroneous diagnostic information. Biochemical investigations, postmortem bacteriology and real-time polymerase chain reaction analysis in cerebrospinal fluid were performed in a series of medico-legal autopsies that included noninfectious causes of death with decomposition, bacterial meningitis without decomposition, bacterial meningitis with decomposition, low respiratory tract infections with decomposition and abdominal infections with decomposition. In noninfectious causes of death with decomposition, postmortem investigations failed to reveal results consistent with generalized inflammation or bacterial infections at the time of death. Real-time polymerase chain reaction analysis in cerebrospinal fluid did not identify the studied bacteria in any of these cases. The results of this study highlight the usefulness of molecular approaches in bacteriology as well as the use of alternative biological samples in postmortem biochemistry in order to obtain suitable information even in corpses with severe decompositional changes.

Protection from lethal gram-negative bacterial sepsis by targeting Toll-like receptor 4.

Toll-like receptor 4 (TLR4), the signal-transducing molecule of the LPS receptor complex, plays a fundamental role in the sensing of LPS from gram-negative bacteria. Activation of TLR4 signaling pathways by LPS is a critical upstream event in the pathogenesis of gram-negative sepsis, making TLR4 an attractive target for novel antisepsis therapy. To validate the concept of TLR4-targeted treatment strategies in gram-negative sepsis, we first showed that TLR4(-/-) and myeloid differentiation primary response gene 88 (MyD88)(-/-) mice were fully resistant to Escherichia coli-induced septic shock, whereas TLR2(-/-) and wild-type mice rapidly died of fulminant sepsis. Neutralizing anti-TLR4 antibodies were then generated using a soluble chimeric fusion protein composed of the N-terminal domain of mouse TLR4 (amino acids 1-334) and the Fc portion of human IgG1. Anti-TLR4 antibodies inhibited intracellular signaling, markedly reduced cytokine production, and protected mice from lethal endotoxic shock and E. coli sepsis when administered in a prophylactic and therapeutic manner up to 13 h after the onset of bacterial sepsis. These experimental data provide strong support for the concept of TLR4-targeted therapy for gram-negative sepsis.

Effective temporary analgesia for severe painful blind eye.

There are various methods of providing pain relief for painful blind eyes. We wish to recommend this effective method of providing temporary analgesia in patients suffering from a severe painful blind eye before undergoing enucleation.

Management of severe pediatric subglottic stenosis with glottic involvement.

OBJECTIVE: We sought to describe our experience in the management of complex glotto-subglottic stenosis in the pediatric age group. METHODS: Between 1978 and 2008, 33 children with glotto-subglottic stenosis underwent partial cricotracheal resection, and they form the focus of this study. They were compared with 67 children with isolated subglottic stenosis (no glottic involvement). The outcomes measured were need for revision open surgical intervention, delayed decannulation (>6 months), and operation-specific and overall decannulation rates. Fisher's exact test was used for comparison of outcomes. RESULTS: Results of preoperative evaluation showed Myer-Cotton grade III or IV stenosis in 32 (97%) patients and grade II stenosis in 1 patient. All patients with glotto-subglottic stenosis were treated with partial cricotracheal resection and simultaneous repair of the glottic pathology. Bilateral fixed vocal cords were seen in 19 (58%) of 33 patients, bilateral restricted abduction was seen in 7 (21%) of 33 patients, and unilateral fixed vocal cord was seen in 7 (21%) of 33 patients. Ten patients underwent single-stage partial cricotracheal resection with excision of interarytenoid scar tissue. The endotracheal tube was kept for a mean period of 7 days as a stent. Twenty-three patients underwent extended partial cricotracheal resection with LT-Mold (Bredam S.A., St. Sulpice, Switzerland) or T-tube stenting. The overall decannulation rate included 26 (79%) patients, and the operation-specific decannulation rate included 20 (61%) patients. CONCLUSIONS: Glotto-subglottic stenosis is a complex laryngeal injury associated with delayed decannulation and decreased overall and operation-specific decannulation rates when compared with those after subglottic stenosis without glottic involvement after partial cricotracheal resection.

Severe primary cytomegalovirus infection in the immunocompetent adult patient: A case series.

Abstract Primary cytomegalovirus (CMV) infection is rare in immunocompetent adults, even rarer in elderly patients. Little is known about the severity of symptoms and the clinical course in this patient group. In children and younger adults, CMV mostly presents as an asymptomatic disease or a self-limiting mild mononucleosis-like syndrome. We describe the clinical course of an unusually severe primary CMV infection in a 69-y-old otherwise healthy man, as well as 6 other severe cases in immunocompetent adults at our institution, and compare them to adult cases from the literature. CMV primary infection and antiviral treatment should be considered in immunocompetent elderly persons presenting with a severe mononucleosis-like syndrome.

Predictors and Moderators of Clinical Outcomes in Adolescents with Severe Mental Disorders After an Assertive Community Treatment.

Previous studies have shown that stressful life events (SLEs), gender, social functioning and pretreatment severity are some of the predictors and/or moderators of treatment outcome in psychiatric care. The current study explored the effect of these predictors and moderators on the treatment outcome related to assertive community treatment (ACT) proposed to young people with severe mental disorders. 98 patients were assessed for externalizing and emotional difficulties, at admission and then at discharge of an ACT. Analyses revealed significant improvements in terms of symptomatology. In particular, regression analyses showed that pretreatment severity is a significant predictor of the outcome on emotional symptoms and is moderated by SLE on the outcome on externalizing symptoms. Furthermore, higher social functioning proved to predict better outcome on externalizing symptoms. Our results further evidence that these factors can explain inter-individual differences in outcome related to ACT. The theoretical and clinical implications of these results are discussed.

Use of recombinant tissue plasminogen activator in children with meningococcal purpura fulminans: a retrospective study.

OBJECTIVE: Meningococcal disease causes septic shock with associated disseminated intravascular coagulation and hemorrhagic skin necrosis. In severe cases, widespread vascular thrombosis leads to gangrene of limbs and digits and contributes to morbidity and mortality. Uncontrolled case reports have suggested that thrombolytic therapy may prevent some complications, and the use of tissue plasminogen activator (t-PA) has been widespread. Our aim was to summarize the clinical outcome and adverse effects where systemic t-PA has been used to treat children with fulminant meningococcemia. DESIGN: International, multiple-center, retrospective, observational case note study between January 1992 and June 2000. SETTING: Twenty-four different hospitals in seven European countries and Australia. PATIENTS: A total of 62 consecutive infants and children with severe meningococcal sepsis in whom t-PA was used for the treatment of predicted amputations and/or refractory shock (40 to treat severe ischemia, 12 to treat shock, and ten to treat both). INTERVENTIONS: t-PA was administered with a median dose of 0.3 mg.kg(-1).hr(-1) (range, 0.008-1.13) and a median duration of 9 hrs (range, 1.2-83). MAIN RESULTS: Twenty-nine of 62 patients died (47%; 95% confidence interval, 28-65). Seventeen of 33 survivors had amputations (11 below knee/elbow or greater loss; six less severe). In 12 of 50 patients to whom t-PA was given for imminent amputation, no amputations were observed. Five developed intracerebral hemorrhages (five of 62, 8%; 95% confidence interval, 0.5-16). Of these five, three died, one developed a persistent hemiparesis, and one recovered completely. CONCLUSIONS: The high incidence of intracerebral hemorrhage in our study raises concerns about the safety of t-PA in children with fulminant meningococcemia. However, due to the absence of a control group in such a severe subset of patients, whether t-PA is beneficial or harmful cannot be answered from the unrestricted use of the drug that is described in this report. Our experience highlights the need to avoid strategies that use experimental drugs in an uncontrolled fashion and to participate in multiple-center trials, which are inevitably required to study rare diseases.

Enhanced expression of 70-kilodalton heat shock protein limits cell division in a sepsis-induced model of acute respiratory distress syndrome.

OBJECTIVE: Fibrotic changes are initiated early in acute respiratory distress syndrome. This may involve overproliferation of alveolar type II cells. In an animal model of acute respiratory distress syndrome, we have shown that the administration of an adenoviral vector overexpressing the 70-kd heat shock protein (AdHSP) limited pathophysiological changes. We hypothesized that this improvement may be modulated, in part, by an early AdHSP-induced attenuation of alveolar type II cell proliferation. DESIGN: Laboratory investigation. SETTING: Hadassah-Hebrew University and University of Pennsylvania animal laboratories. SUBJECTS: Sprague-Dawley Rats (250 g). INTERVENTIONS: Lung injury was induced in male Sprague-Dawley rats via cecal ligation and double puncture. At the time of cecal ligation and double puncture, we injected phosphate-buffered saline, AdHSP, or AdGFP (an adenoviral vector expressing the marker green fluorescent protein) into the trachea. Rats then received subcutaneous bromodeoxyuridine. In separate experiments, A549 cells were incubated with medium, AdHSP, or AdGFP. Some cells were also stimulated with tumor necrosis factor-alpha. After 48 hrs, cytosolic and nuclear proteins from rat lungs or cell cultures were isolated. These were subjected to immunoblotting, immunoprecipitation, electrophoretic mobility shift assay, fluorescent immunohistochemistry, and Northern blot analysis. MEASUREMENTS AND MAIN RESULTS: Alveolar type I cells were lost within 48 hrs of inducing acute respiratory distress syndrome. This was accompanied by alveolar type II cell proliferation. Treatment with AdHSP preserved alveolar type I cells and limited alveolar type II cell proliferation. Heat shock protein 70 prevented overexuberant cell division, in part, by inhibiting hyperphosphorylation of the regulatory retinoblastoma protein. This prevented retinoblastoma protein ubiquitination and degradation and, thus, stabilized the interaction of retinoblastoma protein with E2F1, a key cell division transcription factor. CONCLUSIONS: : Heat shock protein 70-induced attenuation of cell proliferation may be a useful strategy for limiting lung injury when treating acute respiratory distress syndrome if consistent in later time points.

Long-term voice outcome following partial cricotracheal resection in children for severe subglottic stenosis.

OBJECTIVE: To correlate the postoperative voice outcome to preoperative glottic involvement, following partial cricotracheal resection (PCTR) in children. The glottic involvement was analysed based on the extent of subglottic stenosis (SGS) in the endoscopic image and functional dynamic assessment using flexible endoscopy. METHODS: We conducted an interobserver study in which two ENT surgeons, blinded to one another's interpretation, independently rated the extent of SGS based on the endoscopic image along with the dynamic functional airway assessment, of 108 children who underwent PCTR for grade III or IV stenosis. Based on the observation, the glottic involvement was rated into 4 categories: Evaluation of the voice was based on a parent/patient proxy questionnaire sent in 2008 to assess the current functional status of the patient's voice. RESULTS: Among the 77 patients available for long-term outcome with a minimum 1-year follow-up, 31 patients had isolated SGS free from vocal cords (group A) and 30 had SGS reaching the under surface of vocal cords with partial or no impairment of abduction of vocal cords (group B). Twelve patients belonged to group C with posterior glottic stenosis and/or vocal cord fusion (without cricoarytenoid ankylosis) and 4 patients had transglottic stenosis and or/bilateral cricoarytenoid ankylosis (group D). The long-term voice outcome following PCTR as perceived by the parent or patient was normal in 18% (14 of 77 patients) and the remaining 63 patients demonstrated mild to severe dysphonia. Patients belonging to group A and B exhibited either normal voice or mild dysphonia. Patients in group C demonstrated dysphonia, which was moderate in severity in the majority (83%). All patients in group D with transglottic stenosis and/or CAA showed severe dysphonia. CONCLUSION: Children with associated glottic involvement are at high risk for poor voice outcome following PCTR. The severity of dysphonia was found to be proportional to the preoperative glottic involvement. Preoperative rating of the extent of glottic involvement based on endoscopic image and dynamic assessment was found to be useful in prognosticating the voice outcome.

Efficiency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa-responsive patients with Parkinson's disease with severe motor fluctuations: a 2-year follow-up review.

OBJECT: The aim of this study was to evaluate the long-term safety and efficacy of bilateral contemporaneous deep brain stimulation (DBS) in patients who have levodopa-responsive parkinsonism with untreatable motor fluctuations. Bilateral pallidotomy carries a high risk of corticobulbar and cognitive dysfunction. Deep brain stimulation offers new alternatives with major advantages such as reversibility of effects, minimal permanent lesions, and adaptability to individual needs, changes in medication, side effects, and evolution of the disease. METHODS: Patients in whom levodopa-responsive parkinsonism with untreatable severe motor fluctuations has been clinically diagnosed underwent bilateral pallidal magnetic resonance image-guided electrode implantation while receiving a local anesthetic. Pre- and postoperative evaluations at 3-month intervals included Unified Parkinson's Disease Rating Scale (UPDRS) scoring, Hoehn and Yahr staging, 24-hour self-assessments, and neuropsychological examinations. Six patients with a mean age of 55 years (mean 42-67 years), a mean duration of disease of 15.5 years (range 12-21 years), a mean "on/off' Hoehn and Yahr stage score of 3/4.2 (range 3-5), and a mean "off' time of 40% (range 20-50%) underwent bilateral contemporaneous pallidal DBS, with a minimum follow-up period lasting 24 months (range 24-30 months). The mean dose of levodopa in these patients could not be changed significantly after the procedure and pergolide was added after 12 months in five patients because of recurring fluctuations despite adjustments in stimulation parameters. All but two patients had no fluctuations until 9 months. Two of the patients reported barely perceptible fluctuations at 12 months and two at 15 months; however, two patients remain without fluctuations at 2 years. The mean improvements in the UPDRS motor score in the off time and the activities of daily living (ADL) score were more than 50%; the mean off time decreased from 40 to 10%, and the mean dyskinesia and complication of treatment scores were reduced to one-third until pergolide was introduced at 12 months. No significant improvement in "on" scores was observed. A slight worsening after 1 year was observed and three patients developed levodopa- and stimulation-resistant gait ignition failure and minimal fluctuations at 1 year. Side effects, which were controlled by modulation of stimulation, included dysarthria, dystonia, and confusion. CONCLUSIONS: Bilateral pallidal DBS is safe and efficient in patients who have levodopa-responsive parkinsonism with severe fluctuations. Major improvements in motor score, ADL score, and off time persisted beyond 2 years after the operation, but signs of decreased efficacy started to be seen after 12 months.