Pierre Attal

Redefining Parapharyngeal Space Infections

Objectives: Our intent was to review the clinical signs, computed tomography (CT) scans, treatment, and outcome of parapharyngeal space infections (PPIs), and to define 2 types of infections of the parapharyngeal space (PPS) according to the location of the infectious process. Methods: We performed a retrospective analysis of patients hospitalized in a tertiary university hospital with a diagnosis of PPI, abscess, or deep neck abscess between 1988 and 2004. Files and CT scans were reviewed after classification into 2 groups: 1) infection located in the posterior part of the PPS (PostPPI); and 2) infection located in the anterior part of the PPS(AntPPI). Results: Twenty-two patients had a PostPPI; their ages ranged from 10 months to 24 years. Five patients underwent surgical drainage, and 17 others were treated solely with intravenous antibiotic therapy. No pus was found during surgery in 2 patients. The average time of hospitalization was 10 days. Only 1 complication (aspiration pneumonia) was observed. Seven patients had an AntPPI; their ages ranged from 1.5 years to 65 years. All patients underwent surgical drainage, and pus was detected in all cases. The average time of hospitalization was 35 days. Complications (septic shock, respiratory arrest, mediastinitis, pleural empyema, pericarditis) were observed in 4 patients. Conclusions: The term “parapharyngeal abscess” was assigned long before the CT scan era, and was based on physical examination and plain film radiology. In essence, the entity PPS “abscess” or “infection” is composed of 2 different disorders. Infection located in the posterior part of the PPS with no invasion into the parapharyngeal fat and with no extension into other cervical spaces except the adjacent retropharyngeal space may be termed posterior parapharyngeal infection or parapharyngeal lymphadenitis. This is a relatively benign condition, and nonsurgical treatment should be considered. Infection involving the parapharyngeal fat may be termed parapharyngeal abscess or deep neck abscess. Diffusion into the mediastinum and other severe complications are frequent. Urgent surgical drainage is therefore mandatory.

Myosin molecular motor dysfunction in dystrophic mouse diaphragm.

Cross-bridge properties and myosin heavy chain (MHC) composition were investigated in isolated diaphragm from 6-mo-old control ( n = 12) and mdx( n = 12) mice. Compared with control, peak tetanic tension fell by 50% in mdx mice ( P < 0.001). The total number of cross bridges per square millimeter (×109), the elementary force per cross bridge, and the peak mechanical efficiency were lower in mdx than in control mice (each P < 0.001). The duration of the cycle and the rate constant for cross-bridge detachment were significantly lower in mdx than in control mice. In the overall population, there was a linear relationship between peak tetanic tension and either total number of cross bridges per square millimeter or elementary force per cross bridge ( r = 0.996 and r = 0.667, respectively, each P < 0.001). The mdx mice presented a higher proportion of type IIA MHC ( P < 0.001) than control mice and a reduction in type IIX MHC ( P < 0.001) and slow myosin isoforms ( P < 0.01) compared with control mice. We concluded that, in mdx mice, impaired diaphragm strength was associated with qualitative and quantitative changes in myosin molecular motors. It is proposed that reduced force generated per cross bridge contributed to diaphragm weakness in mdx mice.Cross-bridge properties and myosin heavy chain (MHC) composition were investigated in isolated diaphragm from 6-mo-old control (n = 12) and mdx (n = 12) mice. Compared with control, peak tetanic tension fell by 50% in mdx mice (P < 0.001). The total number of cross bridges per square millimeter (x10(9)), the elementary force per cross bridge, and the peak mechanical efficiency were lower in mdx than in control mice (each P < 0.001). The duration of the cycle and the rate constant for cross-bridge detachment were significantly lower in mdx than in control mice. In the overall population, there was a linear relationship between peak tetanic tension and either total number of cross bridges per square millimeter or elementary force per cross bridge (r = 0.996 and r = 0.667, respectively, each P < 0.001). The mdx mice presented a higher proportion of type IIA MHC (P < 0.001) than control mice and a reduction in type IIX MHC (P < 0.001) and slow myosin isoforms (P < 0.01) compared with control mice. We concluded that, in mdx mice, impaired diaphragm strength was associated with qualitative and quantitative changes in myosin molecular motors. It is proposed that reduced force generated per cross bridge contributed to diaphragm weakness in mdx mice.

Congenital tracheoesophageal fistula without esophageal atresia.

The authors report a series of eight cases of isolated tracheoesophageal fistula without esophageal atresia (or an H type fistula), treated in three pediatric ENT departments. This is a rare malformation whose diagnosis requires investigation for associated anomalies. The clinical signs are mainly respiratory but also digestive and the symptomatology can be severe. The diagnosis can be made with a barium swallow combined with cineradiography, but a tracheoesophageal endoscopy remains the investigation of choice. The treatment is surgical. In most cases, the fistula is accessible by a right or left cervicotomy, depending on the surgeons practice, with a much lower postoperative morbidity as compared to a thoracotomy. The postoperative management was straightforward in most of our cases. We discuss the role of gastro-esophageal reflux with respect to postoperative morbidity as well as systematic treatment for reflux peri-operatively. The pros and cons of the various surgical approaches are also discussed.

Pulmonary vascular resistance and compliance relationship in pulmonary hypertension

Right ventricular adaptation to the increased pulmonary arterial load is a key determinant of outcomes in pulmonary hypertension (PH). Pulmonary vascular resistance (PVR) and total arterial compliance (C) quantify resistive and elastic properties of pulmonary arteries that modulate the steady and pulsatile components of pulmonary arterial load, respectively. PVR is commonly calculated as transpulmonary pressure gradient over pulmonary flow and total arterial compliance as stroke volume over pulmonary arterial pulse pressure (SV/PApp). Assuming that there is an inverse, hyperbolic relationship between PVR and C, recent studies have popularised the concept that their product (RC-time of the pulmonary circulation, in seconds) is “constant” in health and diseases. However, emerging evidence suggests that this concept should be challenged, with shortened RC-times documented in post-capillary PH and normotensive subjects. Furthermore, reported RC-times in the literature have consistently demonstrated significant scatter around the mean. In precapillary PH, the true PVR can be overestimated if one uses the standard PVR equation because the zero-flow pressure may be significantly higher than pulmonary arterial wedge pressure. Furthermore, SV/PApp may also overestimate true C. Further studies are needed to clarify some of the inconsistencies of pulmonary RC-time, as this has major implications for our understanding of the arterial load in diseases of the pulmonary circulation. Empiric estimates of pulmonary arterial load are prone to errors and may result in overestimation of RC-time http://ow.ly/QqtAV

A phenotypic and functional characterization of NK cells in adenoids

Adenoids are part of the MALT. In the present study, we analyzed cell surface markers and cytolytic activity of adenoidal NK (A‐NK) cells and compared them with NK cells derived from blood of the same donors (B‐NK). NK cells comprised 0.67% (0.4–1.2%) of the total lymphoid population isolated from adenoids. The majority (median=92%) of the A‐NK cells was CD56brightCD16–. A‐NK cells were characterized by the increased expression of activation‐induced receptors. NKp44 was detected on >60%, CD25 on >40%, and HLA‐DR on >50% of freshly isolated A‐NK cells. Functional assays indicated that the cytotoxic machinery of A‐NK is intact, and sensitive target cells are killed via natural cytotoxicity receptors, such as NKG2D. Carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1; CD66) expression was up‐regulated in 23% (median) of the A‐NK cells by IL‐2 activation but unchanged in B‐NK cells. CEACAM1 inhibited the A‐NK killing of target cells. CXCR4 was expressed on more than 40% A‐NK cells prior to activation. Its ligand, CXCL12, was found in endothelial cells of the capillaries within the adenoid and in cells of the epithelial lining. In addition, A‐NK cells migrated in vitro toward a gradient of CXCL12 in a dose‐responsive manner, suggesting a role for this chemokine in A‐NK cell recruitment and trafficking. We conclude that the A‐NK cells are unique in that they display an activated‐like phenotype and are different from their CD16– B‐NK cell counterparts. This phenotype presumably reflects the chronic interaction of A‐NK cells with antigens penetrating the body through the nasal route.

Growth hormone excess and sternohyoid muscle mechanics in rats

In vitro isotonic and isometric mechanical properties of the sternohyoid (SH) muscle, an upper airway dilator muscle, were studied in rats with a growth hormone (GH)-secreting tumour (GH tumour group; n = 10). The effects of muscle fatigue were also studied. Stress and shortening were measured in muscles contracting from zero load up to isometric load under tetanic conditions. Isometric stress and maximum unloaded shortening velocity were determined and compared with values obtained from control rats (n = 10). Crossbridge kinetics and energetics and mechanical efficiency were calculated from Huxley’s equations. Compared with controls, isometric stress, mechanical efficiency, crossbridge number and crossbridge single force were lower in the GH tumour group. The probability of crossbridge being in the power stroke configuration was lower in the GH tumour group than in controls. Muscle fatigue significantly impaired maximal muscle efficiency and crossbridge single force in the GH tumour group but not in controls. In conclusion, mechanical and energetic properties of the SH muscle and crossbridge properties were worse in the GH tumour group than in controls. This may partly account for impairment of the upper airway dilator muscle function and the increased occurrence of obstructive sleep apnoea in acromegaly.

Starplasty tracheostomy: case series and literature review

ObjectivesThe starplasty tracheostomy (SPT) technique has been suggested to reduce the short-term complications of tracheostomy, including accidental decannulation and pneumothorax. The aim of the present study was to conduct a review of key parameters prior to and following treatment of neonates and children with the SPT technique, including indications, complications, perioperative department stay, and overall length of stay in one University-Affiliated Medical Center.MethodsA retrospective chart review of all children under the age of 18 underwent SPT in a single center between February 2006 and January 2012.ResultsAmong the 39 patients reviewed, the median age at the time of surgery was 14.5 months, ranging from 3 days to 8.8 years. The most common indication for SPT was respiratory insufficiency resulting from central nervous system disorders (15, 38.4%) followed by neuromuscular disorders (14, 35.9%). Ten (25.6%) operations were performed on neonatal intensive care unit (NICU) patients and 29 (74.4%) on pediatric intensive care unit (PICU) patients. The median postoperative hospital stay was 19.5 days (range of 3–207 days); however, the median postoperative stay in the PICU was 13.5 days. There were no decannulations or any other short-term complications after SPT, and no SPT-related deaths occurred.ConclusionsIn our series, pediatric SPT was not associated with any major complications. Therefore, we conclude that SPT should be considered as a safe and advantageous alternative for traditional tracheotomy, especially in patients with low probability of future decannulation, and, therefore, at low risk of a persistent tracheocutaneous fistula.

Custom-made tracheotomy cannula designed by the assistance of virtual bronchoscopy

INTRODUCTION Patients with permanent airway obstruction often require tracheotomy. Usually, a tracheotomy cannula (TC) is necessary to keep open the soft tissues of the neck and the tracheal fenestration. In nonhospitalized patients, a rigid TC (metallic or plastic) with an outer and an inner cannula is frequently used. In case of an obstruction, the inner cannula can be easily removed and cleaned either by the patient or his or her family. The TC is usually chosen according to its shape, diameter, and length. Although a large range of choices of TC is commercially available, patients with a complex anatomical structure may need a custom-made TC. The length and diameter of the TC are usually easily measured, but its shape may be difficult to determine. We used virtual bronchoscopy (VB) for improving the form of a TC in two patients who needed a custom-made TC because of an abnormal airway anatomy. One patient (whose case is described in “Case Report”) was a 23-yearold man with Hunter syndrome. The other patient was a 17-year-old boy with muscular dystrophy, which was causing severe scoliosis. In this patient, the shape of the laryngotracheal complex was completely distorted and it was not possible to insert any commercially available TC. Virtual bronchoscopy was used in both cases in which the unusually complex anatomy prevented an adequate decision on the desired shape, length, and diameter of the custom-made TC. The method in which VB was used for constructing a custom-made TC is described at length. CASE REPORT A 23-year-old man with Hunter syndrome arrived in the emergency room with airway obstruction. He presented for the first time in our department with upper airway obstruction when he was 7 years old. At that time, laryngoscopy showed severe supraglottic and subglottic obstruction and a tracheotomy was performed. Since then, progressive tracheal stenosis and malacia resulting from mucopolysaccharide deposits had developed. Because the obstruction was developing cephalocaudally, several changes of the cannula were required to lengthen it. In addition, the patient also had dwarfism, severe aortic and mitral stenosis with cardiac insufficiency, and a mixed type of hearing loss. However, his mental status was normal, and he was evidently leading quite a normal life. A fiberoptic examination performed through the TC in the emergency room revealed a 3-cm-long stenosis below the tip of the TC, reaching the carina. Other, less significant stenoses were seen inside the right and left sides of the main bronchus. The TC was removed, and a No. 7 (9.6-mm-diameter) endotracheal tube (Portex, SIMS Portex Limited, Hythe, Kent, UK) was inserted as far as the carina. The length of the endotracheal tube from the stoma to the carina was 12.5 cm. Because a ready-made, rigid TC of this length and diameter was unavailable, we were obliged to order a custom-made TC. A three-dimensional computed tomography (CT) scan with VB was then performed with the endotracheal tube in place, and a three-dimensional model of the desired TC was obtained (Fig. 1A–C). Its length, diameter, and shape were sent to Pilling’s Company (Fort Washington, PA), where the custom-made TC was prepared (Fig. 2). The custom-made TC was then inserted into the patient’s stoma. A fiberoptic examination confirmed its location. The patient died 4 years later, of cardiac insufficiency, but no further episodes of airway obstruction occurred during these 4 years.

Screening of acromegaly in adults with obstructive sleep apnea: is it worthwhile?

The prevalence of obstructive sleep apnea (OSA) is very high in the general population (i.e., between the ages of 50 and 70 years, it is around 61 and 37%, in men and women, respectively). It is dependent essentially on age, sex and body mass index [1]. There has been a dramatic increase in the incidence of OSA over the last decades, mostly attributed to an epidemic of obesity [1, 2]. Conversely, the prevalence of acromegaly is very low, ranging from 2.8 to 13.7 cases per 100,000 [3]. This comparative rarity is probably one of the reasons why its diagnosis is challenging and often made only after a delay of many years [3], and due to the very gradual and progressive installation of the dysmorphic syndrome which is characteristic of the disease [4]. According to various (mostly cross-sectional) studies [5–15], OSA affects a majority of patients with acromegaly: on average, OSA, as assessed by polysomnography, is found in 69% of patients with active acromegaly [16] and contributes to a great extent to fatigue in these patients. After effective treatment of acromegaly, either surgical or medical, OSA improves in many patients but may persist in 40% of them [16, 17]. Every patient with acromegaly thus needs to be checked for OSA at least after treatment of their acromegaly, if possible using polysomnography or, eventually, by home (ambulatory) sleep apnea testing [18]. The facial skeletal deformities (particularly of the mandible), and pharyngeal and tongue modifications associated with acromegaly are the major determinants of OSA [9]. However, these anatomical changes are not sufficient to cause OSA, as thickening of soft tissue also plays a major role in the occurrence of OSA in this setting [19]. Generalized soft-tissue thickening is a well-known feature of acromegaly and is related to glycosaminoglycan deposition and increased collagen production by connective tissue, but is also related to tissue edema. Tissue edema is due to increased renal sodium reabsorption by the distal tubules in the kidney, owing to direct stimulation of epithelial sodium channels by GH and IGF-I [20–22]. Overweight, associated with acromegaly in some patients, may also play a major role. This may explain the variable reversibility of OSA after effective treatment for acromegaly [17]. Finally, a role of altered neuromuscular control of the pharyngeal muscles cannot be ruled out. Indeed, in an animal model of acromegaly, we observed myopathy of a dilator muscle of the pharynx [23]. As acromegaly is rare, every means leading to a reduction in the long (5–10 years in general) diagnostic delay would be highly desirable. In this setting, one could ask the question whether it might therefore be worthwhile screening all patients with OSA for acromegaly? In this issue of the Journal, Heinrich et al. [24] have attempted to answer this question by performing a prospective cross-sectional diagnostic study in patients with OSA. By measuring IGF-I in 507 patients with a confirmed diagnosis of OSA, they found 10 patients with increased IGF-I levels, among whom only one did not show suppression of GH under oral glucose tolerance test and had a microadenoma on pituitary MRI, confirming the diagnosis of acromegaly and giving an acromegaly prevalence of 0.2% among this OSA cohort. These results confirm those of a recent French multicenter study, reported by Galerneau et al [25], where a very similar prevalence of acromegaly was found in a comparable group of subjects with OSA. It is interesting to note that, in the end, these results on real populations corroborate the results that would be predicted taking into account the known prevalence of acromegaly in * Philippe Chanson philippe.chanson@bct.aphp.fr

Clinical and Hemodynamic Correlates of Pulmonary Arterial Stiffness in Incident, Untreated Patients With Idiopathic Pulmonary Arterial Hypertension

Background The role of decreased pulmonary arterial (PA) compliance (C), equivalent to increased PA stiffness (1/C), as a critical determinant of right ventricular dysfunction and prognosis has been emphasized in pulmonary arterial hypertension (PAH). Methods This study retrospectively reviewed all incident patients diagnosed with idiopathic PAH according to right heart catheterization who were enrolled in the French Pulmonary Arterial Hypertension Network registry between 2006 and 2016 and who had complete baseline data allowing calculation of stiffness (PA pulse pressure/stroke volume index). Results In the 719 patients included (median age: 66 years; 53.7% female), PA stiffness was 1.49 mm Hg × m2/mL (interquartile ratio: 1.08‐2.04 mm Hg × m2/mL). Stiffness was related to mean pulmonary artery pressure (mPAP) (r2 = 0.33) and heart rate (r2 = 0.15) but not to age or sex. Higher PA stiffness and higher pulmonary vascular resistance (PVR) were documented in high‐risk vs low‐risk patients, as defined according to the European Society of Cardiology/European Respiratory Society guidelines. The dispersion of the PVR × C product was as variable as patient age and mPAP, and C could not be estimated on the basis of PVR alone (95% limits of agreement of the bias: –50% to 54%). Although transplant‐free survival differed across PA stiffness quartiles (P = .04), stiffness was not an independent predictor of long‐term outcome (median follow‐up duration: 2.43 years). Conclusions In incident idiopathic PAH, PA stiffness was related to mPAP and heart rate, and this finding outperformed the potential influences of age and sex. Baseline PA stiffness did not independently predict outcome. The great dispersion of the PVR × C product implied that PVR and PA stiffness were differently affected by the disease process.