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Upper airway collapsibility and cephalometric variables in patients with obstructive sleep apnea.

Increased pharyngeal collapsibility and abnormal anatomic structures have been postulated to contribute to the pathophysiology of obstructive sleep apnea (OSA) syndrome. It is unclear whether the abnormal craniofacial and soft tissue features may affect the pharyngeal collapsibility and contribute to the apnea density. In the present study we examine the relationship between pharyngeal collapsibility and cephalometric variables in a group of 57 male OSA patients. Pharyngeal collapsibility was measured during the night of nasal continuous positive airway pressure (nCPAP) titration by analyzing the pressure-flow relationship. Pharyngeal critical pressure (Pcrit) was calculated as the extrapolated pressure at zero flow. The patients, age 52.0 +/- 9.0 yr, had an average apnea-hypopnea index (AHI) of 72.6 +/- 31.8 and a mean Pcrit of 2.4 +/- 1.0 cm H(2)O. A significant correlation was found between Pcrit and the soft palate length (SPl) (r = 0.27, p = 0.04), the distance from the hyoid bone to the posterior pharyngeal wall (H-Ph) (r = 0. 29, p = 0.03), and the distance from the hyoid bone to posterior nasal space (H-Pns) (r = 0.32, p = 0.02). While in obese patients Pcrit was related to SPl and neck circumference, the distance of the hyoid bone to the mandibular plane (H-MP) affected Pcrit in nonobese patients. Our results show that both pharyngeal soft tissue abnormalities and the lower position of the hyoid bone affect Pcrit in OSA patients, suggesting that an anatomic narrowing contributes to the upper airway collapsibility.

Adult↗

Prone position increases collapsibility of the passive pharynx in infants and small children.

On the basis of two observations that avoiding prone sleeping decreased incidence of sudden infant death syndrome and that obstructive sleep apnea is closely linked with the syndrome, we hypothesized that the prone position may increase upper airway collapsibility in infants and small children. Passive pharyngeal collapsibility of 19 infants and small children (10-101 weeks old) was examined in three postures: supine with face straight up, supine with neck rotated, and prone with neck rotated. The collapsibility was evaluated with the maximal distension of the most collapsible region, pharyngeal stiffness, and pharyngeal closing pressure, estimated from static pressure-area relationship of the passive pharynx. No significant changes in pharyngeal stiffness were detected; however, maximal distension was reduced in the prone position (mean +/- SD, 0.56 +/- 0.26 versus 0.44 +/- 0.20 cm(2); supine with face straight up versus prone position, p < 0.05). Pharyngeal closing pressure increased at neck rotation in the supine position (-4.5 +/- 2.4 versus -2.8 +/- 2.3 cm H(2)O; supine with face straight up versus supine with neck rotated, p < 0.05), and a further increase was observed in the prone position (-0.3 +/- 2.9 cm H(2)O, p < 0.05 versus supine with neck rotation). Pharyngeal closing pressure in the prone position was above atmospheric pressure in half of our subjects, whereas all subjects had negative pharyngeal pressure in the supine position. We conclude that the prone position increases upper airway collapsibility, although the mechanism is yet unclear.

Airway Resistance↗

In vitro experiments on axonal guidance and growth-cone collapse.

In the retinotectal projection, nasal retinal axons project to posterior tectum, while temporal axons project to the anterior part of the tectum. In in vitro experiments, a similar specificity can be observed: the nasal and temporal retinal axons can be guided by tectal membrane components so that, for example, temporal retinal axons, when growing on a striped substratum consisting of anterior and posterior tectal membranes, express a very strong preference for the anterior stripes. This preference is not due to attractivity of anterior membranes but rather to avoidance of posterior material, although the pure posterior membranes are a very good substratum for growth of temporal axons. The repellent guidance molecule has been identified. Interestingly, besides guidance this molecule causes another reaction: when growing temporal axons are exposed to medium containing either posterior membranes or artificial lipid vesicles containing the repellent guidance molecule, the axonal growth cones collapse. As in guidance, there is a clear regional specificity: e.g. the repellent guidance molecule derived from posterior tectum induces collapse of temporal but not of nasal axons. Since the guiding and the collapse-inducing activity are expressed by one and the same glycoprotein molecule (Mr 33 x 10(3), linked to the membrane by phosphatidylinositol) and since another molecule has been identified by Keynes' group which also expresses both guiding and collapse-inducing activity, one might speculate that axonal guidance and axonal collapse have something in common. Models of axonal guidance will be discussed.

Animals↗

Collapse of a stent-graft following treatment of a traumatic thoracic aortic rupture.

PURPOSE: To report a collapsed stent-graft used to treat a traumatic aortic rupture. CASE REPORT: A Gore TAG stent-graft was placed in a 20-year-old man with multiple injuries. Postimplantation computed tomographic angiography (CTA) demonstrated no contrast extravasation and total exclusion of the traumatic rupture. Routine CTA 3 months after implantation revealed a collapsed stent-graft located in the outer curve of the distal aortic arch. A Talent stent-graft was placed successfully within the collapsed prosthesis. Postimplantation CTA demonstrated no contrast extravasation and good apposition of the endograft to the aortic wall. At 6 months, the repair remains secure; there is no sign of graft collapse or endoleak. CONCLUSIONS: Collapse of stent-grafts can occur after treatment for traumatic aortic ruptures; endovascular methods can be used to restore a satisfactory luminal contour.

Accidents, Traffic↗

Tube collapse and valve closure in ambulatory venous pressure regulation: studies with a mechanical model.

PURPOSE: To determine the role of valve closure and column segmentation in ambulatory venous pressure regulation. METHODS: Using a mechanical model consisting of a graduated adjustable valve and a collapsible tube, we studied the differential effects of valve closure and tube collapse on venous pressure regulation. By utilizing materials with differing wall properties for the infravalvular tube, the influence of wall property changes on tube function and pressure regulation was explored. RESULTS: Valve closure, per se, does not cause venous pressure reduction. Collapse of the tube below the valve is the primary pressure regulatory mechanism. The nonlinear volume-pressure relationship that exists in infravalvular tubes confers significant buffering properties to the collapsible tube, which tends to retain a near-constant pressure for a wide range of ejection fractions, residual tube volumes, and valve leaks. Changes in tube wall property affect this buffering action, at both the low and high ends of the physiological venous pressure range. CONCLUSIONS: The valve and the infravalvular venous segment should be considered together in venous pressure regulation. Tube collapse of the segment below the valve is the primary pressure regulatory mechanism. An understanding of the hydrodynamic principles involved in pressure regulation derived from this model will provide the basis for construction of more complex models to explore clinical physiology and dysfunction.

Biomechanical Phenomena↗

The dysregulated podocyte phenotype: a novel concept in the pathogenesis of collapsing idiopathic focal segmental glomerulosclerosis and HIV-associated nephropathy.

Podocytes are highly differentiated, postmitotic cells, whose function is largely based on their complex cytoarchitecture. The differentiation of podocytes coincides with progressive expression of maturity markers, including WT-1, CALLA, C3b receptor, GLEPP-1, podocalyxin, and synaptopodin. In collapsing forms of focal segmental glomerulosclerosis (FSGS), including idiopathic FSGS and HIV-associated nephropathy, podocytes undergo characteristic, irreversible ultrastructural changes. This study analyzes the expression pattern of the above differentiation markers and of the proliferation marker Ki-67 in collapsing idiopathic FSGS and HIV-associated nephropathy compared with minimal change disease, membranous glomerulopathy, as well as normal adult and fetal human kidney. In minimal change disease and membranous glomerulopathy, all mature podocyte markers were retained at normal levels despite severe proteinuria and foot process fusion; no cell proliferation was observed. In contrast, in collapsing idiopathic FSGS and HIV-associated nephropathy, there was disappearance of all markers from all collapsed glomeruli and of synaptopodin from 16% of noncollapsed glomeruli. This phenotypic dysregulation of podocytes was associated with cell proliferation in both diseases. It is concluded that the loss of specific podocyte markers defines a novel dysregulated podocyte phenotype and suggests a common pathomechanism in collapsing FSGS, whether idiopathic or HIV-associated.

AIDS-Associated Nephropathy↗

Liver disease in dogs with tracheal collapse.

BACKGROUND: Hepatopathy in dogs with chronic respiratory diseases is poorly recognized. The aim of this study was to evaluate liver parameters alanine transferase, alkaline phosphatase, and glutamate dehydrogenase, as well as basal and stimulated bile acid concentration, in dogs with tracheal collapse. HYPOTHESIS: Dogs with tracheal collapse have hepatopathy. ANIMALS: 26 dogs with tracheal collapse. MATERIALS AND METHODS: Gall bladder contraction was stimulated by intramuscular injection of a synthetic cholecystokinin analogue (ceruletide). Twelve healthy Beagle dogs and 30 dogs of various breeds investigated previously without evidence of hepatic, gastrointestinal, or respiratory diseases served as control. Amelioration of liver variables was assessed after stent implantation. RESULTS: Twelve of 26 (46%) dogs had increased serum activity of 2 or more liver enzymes. Serum basal bile acid concentrations were high in 24 of 26 dogs. Twenty- and 40-minute stimulated bile acids were significantly higher in dogs with tracheal collapse (64.2 +130.0/-43.0 micromol/L and 82.6 +164.0/-57.1 micromol/L) compared to the control dogs (7.0 +/- 3.6 micromol/L and 6.4 +/- 3.5 micromol/L). All twelve dogs reevaluated after a median of 58 days (48-219 days) had a normal breathing pattern and significantly decreased 20 and 40 minutes stimulated bile acids (50.0 +92.7/-32.8 micromol/L, 52.8 +97.6/-34.3 micromol/L; P = .0043), whereas plasma liver enzyme activities were not significantly influenced. CONCLUSION AND CLINICAL IMPORTANCE: There was a significant hepatic dysfunction in the majority of dogs with a tracheal collapse. Liver function should be routinely assessed in dogs with severe respiratory disease.

Alanine Transaminase↗

Rotational acetabular osteotomy for osteonecrosis with collapse of the femoral head in young patients.

BACKGROUND: While rotational acetabular osteotomy has been reported to be successful for the treatment of osteoarthritis of the dysplastic hip, little is known about its efficacy in the treatment of osteonecrosis of the femoral head. METHODS: We retrospectively reviewed the results for a consecutive series of twenty-one patients (twenty-five hips) who had undergone rotational acetabular osteotomy between 1995 and 2001 for the treatment of extensive osteonecrosis of the femoral head associated with collapse. All but two of the patients had a history of steroid therapy as part of a treatment regimen for various diseases. At the time of surgery, the mean age of the five men and sixteen women was 29.0 years. The mean duration of follow-up was forty-nine months. No patient was lost to follow-up. The lesions were classified according to the staging system described by Steinberg et al., and the extent of necrosis was measured with use of the criteria described by Kerboul et al. Clinical evaluation was performed with use of the scoring system of Merle d'Aubigne and Postel. Radiographic evaluation was performed with use of yearly serial anteroposterior and lateral plain radiographs. RESULTS: The mean Merle d'Aubigne and Postel score improved from 11.3 points preoperatively to 14.9 points at the time of the final follow-up (p < 0.001). The mean pain score improved from 3.0 to 5.6 points (p < 0.001). However, the mean mobility score was 5.3 points preoperatively but only 4.9 points postoperatively (p = 0.1). All of the osteotomy sites showed radiographic evidence of osseous union at the time of the latest follow-up. Collapse of the femoral head progressed in seven hips, but in six of these hips the change in the extent of collapse was <2 mm. CONCLUSIONS: In the present study of young patients with extensive osteonecrosis and collapse of the femoral head, rotational acetabular osteotomy was associated with symptomatic relief and absence of substantial collapse of the femoral head at the time of early to intermediate-term follow-up.

Acetabulum↗

Clinical and microbiologic findings in dogs with bronchoscopically diagnosed tracheal collapse: 37 cases (1990-1995).

OBJECTIVE: To investigate the role of bacteria in bronchoscopically diagnosed tracheal collapse in dogs by evaluating qualitative results of bacteriologic cultures. DESIGN: Retrospective study. ANIMALS: 37 dogs with tracheal collapse. PROCEDURE: Clinical records for dogs with tracheal collapse confirmed with bronchoscopy were reviewed. A protected catheter brush was used to obtain samples for bacteriologic culture from the large airways. RESULTS: Results of bacterial culture were negative for 5 of 29 dogs. For 24 dogs, 1 (n = 10), 2 (6), or > or = 3 (8) species of bacteria were isolated. Pseudomonas spp were isolated most frequently (17/29), and a single Pseudomonas sp grew in 7 samples. Other bacteria included Enterobacter spp (4/29), Citrobacter spp (3/29), and Moraxella spp, Klebsiella spp, Bordetella spp, or Acinetobacter spp (2/29 dogs each). Anaerobic and aerobic cultures yielded positive results in samples from 2 dogs. Cytologic results were available for 13 dogs with positive results of bacteriologic culture; epithelial cells were reported most commonly. Five samples had a small number of neutrophils; bacteria were identified cytologically in 2 of 5 samples that contained neutrophils. Bacteria were also seen in 2 samples that lacked inflammatory cells. CONCLUSIONS AND CLINICAL RELEVANCE: Bacteria are commonly isolated from samples obtained via airway brushing in dogs with tracheal collapse; however, in the absence of cytologic confirmation of inflammation or infection, an association between bacteria and clinical signs of tracheal collapse cannot be established.

Animals↗

Anterior expandable strut cage replacement for osteoporotic thoracolumbar vertebral collapse.

OBJECT: The authors investigated the usefulness of using an expandable cage strut in anterior reconstruction after osteoporotic vertebral collapse in patients with neurological deficits. METHODS: Twenty-eight patients who had undergone expandable cage strut-augmented anterior thoracolumbar reconstruction participated in a follow-up review for a mean of 4.9 years. Radiographs were reviewed for kyphosis, lateral tilt of the implant, cage subsidence, the presence of a solid fusion mass, and instrumentation failure. Changes in neurological status and visual analog scale (VAS) pain score, as well as technique-related complications, were examined. The mean angles +/- the standard deviations of kyphosis correction 4 to 6 weeks after surgery and at final follow-up examination were 10.4 +/- 7.6 degrees and 5.6 +/- 6.0 degrees, respectively. The mean subsidence of the expandable cage within the adjacent vertebrae was 2.5 +/- 3.0 mm at the final follow-up examination. Neurological improvement at the final follow up was more significant in patients with Type I (wedge-type) than Type 2 (flat-type) (p = 0.037) or Type 3 (concave-type) (p = 0.006) vertebral collapse. Follow-up VAS scores were significantly higher in patients with Type 1 than Type 3 collapse (p = 0.012). In all cases the authors observed solid union with incorporation of the cage. There were no surgery-related complications. CONCLUSIONS: An expandable titanium cage strut seems useful in vertebral body replacement in patients with osteoporotic thoracolumbar collapse. Favorable results were obtained in cases of Type I collapse (wedge type) in which the middle and posterior columns remained comparatively intact.

Aged↗

Rac1-mediated endocytosis during ephrin-A2- and semaphorin 3A-induced growth cone collapse.

Negative guidance molecules are important for guiding the growth of axons and ultimately for determining the wiring pattern in the developing nervous system. In tissue culture, growth cones at the tips of growing axons collapse in response to negative guidance molecules, such as ephrin-A2 and semaphorin 3A. The small GTPase Rac1 is involved in growth cone collapse, but the nature of its role is not clear. Rac1 activity assays showed that Rac1 is transiently inactivated after treatment with ephrin-A2. Ephrin-induced growth cone collapse, however, correlated with resumption of Rac1 activity. We demonstrate that Rac1 is required for endocytosis of the growth cone plasma membrane and reorganization of F-actin but not for the depolymerization of F-actin during growth cone collapse in response to ephrin-A2 and semaphorin 3A. Rac1, however, does not regulate constitutive endocytosis in growth cones. These findings show that in response to negative guidance molecules, the function of Rac1 changes from promoting actin polymerization associated with axon growth to driving endocytosis of the plasma membrane, resulting in growth cone collapse. Furthermore, Rac1 antisense injected into the embryonic chick eye in vivo caused the retinotectal projection to develop without normal topography in a manner consistent with Rac1 having an obligatory role in mediating ephrin signaling.

Actins↗

Thrombin-induced growth cone collapse: involvement of phospholipase A(2) and eicosanoid generation.

The studies presented here explore intracellular signals resulting from the action of repellents on growth cones. Growth cone challenge with thrombin or thrombin receptor-activating peptide (TRAP) triggers collapse via a receptor-mediated process. The results indicate that this involves activation of cytosolic phospholipase A(2) (PLA(2)) and eicosanoid synthesis. The collapse response to repellents targets at least two functional units of the growth cone, the actin cytoskeleton and substratum adhesion sites. We show in a cell-free assay that thrombin and TRAP cause the detachment of isolated growth cones from laminin. Biochemical analyses of isolated growth cones reveal that thrombin and TRAP stimulate cytosolic PLA(2) but not phospholipase C. In addition, thrombin stimulates synthesis of 12- and 15-hydroxyeicosatetraenoic acid (HETE) from the released arachidonic acid via a lipoxygenase (LO) pathway. A selective LO inhibitor blocks 12/15-HETE synthesis in growth cones and inhibits thrombin-induced growth cone collapse. Exogenously applied 12(S)-HETE mimics the thrombin effect and induces growth cone collapse in culture. These observations indicate that thrombin-induced growth cone collapse occurs by a mechanism that involves the activation of cytosolic PLA(2) and the generation of 12/15-HETE.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Growth cone collapse induced by semaphorin 3A requires 12/15-lipoxygenase.

Detection of a repellent factor, such as a semaphorin (Sema), causes localized collapse of the growth cone and directs the neurite away from the repellent. Growth cone collapse results from concomitant cytoskeletal rearrangements and detachment of adhesion sites from the extracellular matrix, via mostly unknown signaling mechanisms. In cultures of dorsal root ganglion neurons, we found that Sema3A treatment stimulates the synthesis of the eicosanoid, 12(S)-hydroxyeicosatetraenoic acid (HETE), whereas Sema3A-induced growth cone collapse is prevented when 12(S)-HETE synthesis is blocked with an inhibitor of 12/15-lipoxygenase (LO). Exogenously applied product of 12/15-LO, 12(S)-HETE, mimics Sema3A-induced collapse. As observed by interference reflection and confocal microscopy, 12(S)-HETE causes the loss of growth cone adhesion sites. The adhesion site effect seems partially independent of the actin cytoskeleton because growth cones treated with Sema3A and 12/15-LO inhibitor remain spread despite actin cytoskeleton loss. These studies demonstrate that 12/15-LO activity is a necessary step in Sema3A collapse signaling in growth cones and suggest a mechanism for its action.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

[The injection of acrylic bone cement prevents bone collapse in the intercalar bones lacking bony support: an experimental sheep semilunar bone model].

OBJECTIVES: In a sheep semilunar bone model, we investigated whether collapse in the intercalar bones lacking bony support could be prevented by the injection of acrylic bone cement. METHODS: The study included 16 limbs of eight sheep. Preoperatively, anteroposterior and lateral views of the carpal joints in the fore limbs were obtained. The animals were divided into four groups. In group 1 (n=3) no surgical procedure was performed in the right semilunar bones, whereas the periosteum on the contralateral side was elevated (group 2; n=3). The first two groups were left as controls. In Group 3 (n=5) the left semilunar bones were filled with acrylic bone cement following decancellation of the bone, while the right semilunar bones were left decancellated (group 4; n=5). The sheep were monitored for three months. Radiographs of the carpal joints were obtained to evaluate collapse occurrence in the semilunar bones. Thereafter, the animals were sacrificed and the semilunar bones were excised for biomechanical and histological examinations. Osteonecrosis and cartilage damage were sought and resistance to compressive forces was investigated. RESULTS: Radiologically, the extent of collapse was statistically significant in the semilunar bones in group 4 (p<0.05). The use of acrylic bone cement was found to prevent collapse in group 3, with no significant difference being noted between preoperative and postoperative semilunar bone heights (p>0.05). Biomechanically, the least resistance to compressive forces was measured in group 4 (p<0.05). Histologically, cartilage damage and osteonecrosis were only seen in group 4. CONCLUSION: Our data suggest that the use of acrylic bone cement prevents collapse in the semilunar bones, without inducing any cartilage damage or osteonecrosis.

Animals↗

Magnetic resonance imaging and scintigraphy of avascular necrosis of the femoral head. Prediction of subsequent segmental collapse.

For the purpose of an effective management of patients at high risk for nontraumatic avascular necrosis of the femoral head (ANFH), it is expedient to examine the femoral heads of patients most likely to undergo subsequent segmental collapse. The purpose of this study was to evaluate the ability of magnetic resonance imaging (MRI) and radionuclide bone scanning (RS) to predict segmental collapse of the femoral head at the roentgenographically normal stage. Fifty-five hips in 37 patients at risk for ANFH and having normal roentgenograms were included in this study. Magnetic resonance imaging was performed in all hips and RS in 29 hips. The patients were observed during a period of more than two years without any invasive intervention, and nine femoral heads manifested collapse during this period. Predictive values for subsequent segmental collapse of a positive test of MRI and RS were 31% and 13%, respectively, whereas those indicative of a negative test were 100% and 76%, respectively. Magnetic resonance imaging was more useful than RS in detecting patients in need of intensive follow-up examination. In particular, a bandlike area of low intensity that traversed the femoral head in midcoronal slices on MR images seemed to be a significant indicator of subsequent collapse.

Adult↗

[Significance of expiratory bronchiolar collapse symptoms in the diagnosis of emphysema].

A club-shaped resistance curve as recorded using wholebody plethysmography, as an expression of expiratory bronchial collapse is often interpreted as a sign of pulmonary emphysema. Within the framework of a prospective study involving 32 consecutive patients, a quantification of the resistance loops was carried out. The results obtained indicate that dynamic airway collapse is not specific to emphysema. Rather, there is a highly significant correlation between the degree of bronchial collapse and the elevation of total lung capacity irrespective of whether the latter is due to a reversible hyperinflation associated with bronchospasm or to emphysema of the lungs. It can, however, be seen that, in patients with reversible hyperinflation, intensive anti-obstructive treatment also leads to a decrease in, or the disappearance of, the signs of bronchiole collapse with simultaneous decrease in TLC. We conclude from this that a repeat wholebody plethysmographic examination following a lengthy period of treatment is suitable for distinguishing between bronchiole collapse in reversible hyperinflation and emphysema.

Aged↗

Rac1 mediates collapsin-1-induced growth cone collapse.

Collapsin-1 or semaphorin III(D) inhibits axonal outgrowth by collapsing the lamellipodial and filopodial structures of the neuronal growth cones. Because growth cone collapse is associated with actin depolymerization, we considered whether small GTP-binding proteins of the rho subfamily might participate in collapsin-1 signal transduction. Recombinant rho, rac1, and cdc42 proteins were triturated into embryonic chick (DRG) neurons. Constitutively active rac1 increases the proportion of collapsed growth cones, and dominant negative rac1 inhibits collapsin-1-induced collapse of growth cones and collapsin-1 inhibition of neurite outgrowth. DRG neurons treated with dominant negative rac1 remain sensitive to myelin-induced growth cone collapse. Similar mutants of cdc42 do not alter growth cone structure, neurite elongation, or collapsin-1 sensitivity. Whereas the addition of activated rho has no effect, the inhibition of rho with Clostridium botulinum C3 transferase stimulates the outgrowth of DRG neurites. C3 transferase-treated growth cones exhibit little or no lamellipodial spreading and are minimally responsive to collapsin-1 and myelin. These data demonstrate a prominent role for rho and rac1 in modulating growth cone motility and indicate that rac1 may mediate collapsin-1 action.

ADP Ribose Transferases↗

Preliminary results of collapse therapy with plombage for pulmonary disease caused by multidrug-resistant mycobacteria.

Seven patients underwent collapse therapy with polystyrene sphere plombage for pulmonary disease caused by multidrug-resistant mycobacteria. Four patients were infected with multidrug-resistant strains of Mycobacterium tuberculosis, two with Mycobacterium xenopi, one with Mycobacterium avium. All patients were heavily pretreated before surgery, had extensive, bilateral cavitary disease and were considered unsuitable for resection because of extensive disease or functional respiratory impairment. Six patients had active disease at time of surgery. Collapse therapy with insertion of six to 18 spheres resulted in long-standing bacteriological conversion in six patients. Collapse therapy was unilateral in six and bilateral in one. No immediate postoperative complication or death was observed. Hospital stay was short (mean 12 d). Collapse therapy is a conservative alternative therapy in patients with pulmonary disease caused by multidrug-resistant mycobacteria at high risk of treatment failure considered unsuitable for pulmonary resection.

Adult↗