Potential advantages and limitations of the Leo stent in endovascular treatment of complex cerebral aneurysms

Objective

The Leo self-expandable stent is a new retractable stent that is delivered via a conventional catheter. The aim of this study was to evaluate the use of this stent for endovascular treatment of complex aneurysms.

Methods

Twenty-eight complex cerebral aneurysms (27 saccular and 1 fusiform) in 28 patients were treated electively. They were located at the internal carotid artery (17), basilar trunk (3), anterior cerebral artery (1), anterior communicating artery (3), vertebral artery (2) and middle cerebral artery (2). One aneurysm exhibited recanalization after primary endovascular treatment without stent. Clinical outcome was assessed with the modified Glasgow Outcome Scale.

Results

Deployment of Leo stent was successful in 26 lesions, and difficulties in stent positioning due to tortuous cerebral circulation in 2 cases, which were treated with Neuroform stent. Additional coil embolization was performed in 26 lesions. No permanent neurological deficits were encountered consequent to endovascular procedure. Complete or partial occlusion immediately after stent deployment was achieved in all aneurysms. There was no immediate coil embolization was chosen in 3 cases because of subsequent reduced filling of the aneurysms with contrast agent on angiograms. There were 3 asymptomatic parent artery occlusion related to the deployment of the Leo stent, one stent migration. Follow-up revealed patent stents in the remaining cases. No angiographic recurrences arose.

Conclusion

The Leo stent is very useful for endovascular treatment of complex cerebral aneurysms because it is easy to navigate and place precisely. A drawback is that in-stent thrombosis caused by stent placement and stiffer delivery catheters to place larger stents.     

Percutaneous ultrasound-guided thrombin injection for the treatment of iatrogenic femoral artery pseudoaneurysms

Purpose

To audit our experience with ultrasound-guided thrombin injection for the treatment of iatrogenic femoral artery pseudoaneurysms.

Methods

A retrospective study of 85 consecutive patients undergoing percutaneous ultrasound-guided thrombin injection of post-catheterization femoral pseudoaneurysms during the period January 2002 to May 2007.

Results

Pseudoaneurysms had a mean maximum diameter of 3.3 cm (range 1.0-7.6 cm) and a mean neck width of 3.4 mm (range 1.0-7.0 mm). No statistically significant correlation existed between maximum diameter and neck width (Kendall's rank correlation tau b = −0.09, p = 0.5). The median dose of thrombin injected was 425 U (range 100-1500 U). The procedure resulted in complete sac thrombosis in 81 (95%) patients. Seventy-nine pseudoaneurysms thrombosed immediately after one injection, whereas two required a second thrombin injection. There were no procedural complications. The maximum diameter of the pseudoaneurysm was predictive of procedural success (Wilcoxon's rank sum test, p = 0.001) and of the 5 patients with a pseudoaneurysm measuring ≥6 cm, ultrasound-guided thrombin injection was unsuccessful in 4 (4/5 versus 0/80, p < 0.0001, Fisher's exact test). Three of these necessitated implantation of a stent-graft, whereas one required repeated thrombin injection and coil placement. In contrast, the pseudoaneurysm neck width did not seem to relate to the success of the procedure.

Conclusion

Percutaneous ultrasound-guided thrombin injection of is a quick, effective and safe treatment for iatrogenic femoral pseudoaneurysms. For larger pseudoaneurysms, although it is worth attempting more than one thrombin injection, endovascular repair may eventually be required.     

Value of diffusion-weighted MR imaging in the differentiation between benign and malignant cervical lymph nodes

Purpose

To evaluate echo-planar diffusion-weighted MR imaging (DWI) in the differentiation between benign and malignant cervical lymph nodes.

Materials and methods

35 consecutive patients with 55 enlarged (>10 mm) cervical lymph nodes underwent MR imaging at 1.5-T. DWI was performed using a single-shot echo-planar (SSEPI) MR imaging sequence with b values (b: diffusion factor) of 0, 500 and 1000 s/mm². Apparent diffusion coefficient (ADC) maps were reconstructed for all patients and ADC values were calculated for each lymph node. Imaging results were correlated with histopathologic findings after neck dissection or surgical biopsy, findings in PET/CT or imaging follow-up. Mann-Whitney test was used for statistical analysis and a receiver operating characteristic (ROC) curve analysis was performed.

Results

Cervical lymph node enlargement was secondary to metastases from squamous cell carcinomas [n = 25], non-Hodgkin’s lymphoma [n = 6], reactive lymphadenitis [n = 20], cat scratch lymphadenitis [n = 2] and sarcoidosis [n = 2]. The mean ADC values (×10⁻³ mm²/s) were 0.78 ± 0.09 for metastatic lymph nodes, 0.64 ± 0.09 for lymphomatous nodes and 1.24 ± 0.16 for benign cervical lymph nodes. ADC values of malignant lymph nodes were significantly lower than ADC values of benign lymph nodes. 94.3% of lesions were correctly classified as benign or malignant using a threshold ADC value of 1.02 × 10⁻³ mm²/s.

Conclusion

According to our first experience, DWI using a SSEPI sequence allows reliable differentiation between benign and malignant cervical lymph nodes.     

Coil embolization of internal mammary artery injured during central vein catheter and cardiac pacemaker lead insertion

Purpose

This study describes several cases of endovascular coil embolization of the proximal internal mammary artery injured by blind approach to the subclavian vein for central venous catheter or pacemaker lead insertion.

Materials and methods

We conducted a retrospective analysis of five patients with iatrogenic arterial lesions of the internal mammary artery (IMA). The lesions occurred in three patients from a puncture of the subclavian vein during insertion of a central venous catheter and in two patients from a puncture of the subclavian vein for insertion of a pacemaker lead. Four patients had acute symptoms of bleeding with mediastinal hematoma and hematothorax and one patient was investigated in a chronic stage. A pseudoaneurysm was detected in all five patients. All four acute and hemodynamic unstable patients required hemodynamic support.

Results

In all patients, embolization was performed using a coaxial catheter technique, and a long segment of the IMA adjacent distally and proximally to the source of bleeding was occluded with pushable microcoils. In one patient, additional mechanically detachable microcoils were used at the very proximal part of the IMA.Microcoil embolization of the IMA was successful in all patients, and the source of bleeding was eliminated in all patients.

Conclusion

Transarterial coil embolization is a feasible and efficient method in treating acute bleeding and pseudoaneurysm of the IMA and should be considered if mediastinal hematoma or hemathorax occurs after blind puncture of the subclavian vein.     

Percutaneous treatment of non-contained lumbar disc herniation by injection of oxygen-ozone combined with collagenase

Purpose

To evaluate the therapeutic results of oxygen-ozone combined collagenase injection for the treatment of lumbar disc herniation compared to the surgery. And to explore the role of this minimally invasive treatment as an alternative to disc surgery.

Materials and methods

Two groups of patients (n = 108) were treated with different ways respectively. Minimally invasive group of patients was treated with the injection of oxygen-ozone combined with collagenase into the lumbar disc or the epidural space; the other group was treated with traditional surgery. After the treatment, the patients were followed-up and the therapeutic effect was assessed at 2 weeks, 3 and 12 months by the modified Macnab criteria.

Results

The success rate was 86.11% and 88.89% in minimally invasive group at 3 and 12 months respectively, while 92.59% and 95.37% in surgical group. There was no statistically significant difference between two groups at 3 and 12 months (P = 0.123, P = 0.08). However, the surgical group produced a statistically significant greater improvement for back pain and disability in the first few weeks (P = 0.0001). The success rate was 51.86% and 85.18% at 2 weeks in minimally invasive group and surgical group respectively. No serious complication occurred in this group.

Conclusions

The combination of the oxygen-ozone with collagenase shows significant reductions in pain and improvements in function at 3 and 12 months, it can be considered as an option for the treatment of non-contained lumbar disc herniation instead of surgery.     

Quantification of synovitis in Rheumatoid Arthritis: Do we really need quantitative measurement of contrast-enhanced ultrasound?

Objective

The quantification of synovitis is of great significance for adequate therapy management and follow-up in patients with Rheumatoid Arthritis (RA). The purpose of this study was to validate a semi-quantitative Power Doppler (PD) scoring system by comparing the PD scores to the objective measurement of the synovial inflammation using dynamic contrast-enhanced Pulse-Inversion Harmonic Imaging (PIHI).

Materials and methods

In 27 patients with RA, two radiologists performed semi-quantitative scoring of a PD examination, using a four-point scale from 0 to 3, in the metacarpophalangeal joints, proximal interphalangeal joints, and the wrists. The scores were compared to the area under the time-echo intensity curves obtained by contrast-enhanced PIHI examination. The interobserver agreement for PD scoring was evaluated using the Cohen's kappa test.

Results

Preliminary results showed that the area under the curve of dynamic measurements of PIHI tended to correlate with PD scores. The interobserver agreement for PD scoring was good (κ = 0.768).

Discussion

Based on comparisons with dynamic contrast-enhanced PIHI, semi-quantitative PD scoring might meet the criteria for a reliable, reproducible, and practical scoring system. Although further studies that would include a larger study population are required, our preliminary results show that PIHI may not provide a real benefit for quantification of synovitis in day-to-day practice.     

Treatment response evaluation with three-dimensional contrast-enhanced ultrasound for liver cancer after local therapies

Objective

To investigate the potential usefulness of three-dimensional contrast-enhanced ultrasound (3D-CEUS) in evaluating the treatment response for liver cancer after local therapies.

Methods

A total of 107 lesions in 95 consecutive patients with liver cancer underwent local therapies and thereafter received low acoustic power 3D-CEUS examination. The LOGIQ 9 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The image quality of 3D-CEUS images was evaluated and the influence of 3D-CEUS to clinical outcome was investigated.

Results

The image quality of 3D-CEUS was defined as high in 102 (102/107, 95.3%) lesions and common in 5 (5/107, 4.7%) lesions. 3D-CEUS did not change the diagnosis in any patient compared with 2D-CEUS. However, 3D-CEUS changed the management in 3 (2.8%) of 107 lesions, increased confidence but made no change in diagnosis in 85 (79.5%) lesions, added some information but did not change management or diagnosis in 15 (14.0%), and made no change in 4 (3.7%), respectively, in comparison with 2D-CEUS.

Conclusion

3D-CEUS enhances the diagnostic confidence in the majority of the patients and even changes the management in some patients. 3D-CEUS has potential usefulness in evaluating treatment response for liver cancer after local therapies.     

Correlation of olfactory dysfunction of different etiologies in MRI and comparison with subjective and objective olfactometry

Background

The clinical diagnosis of olfactory dysfunction of different etiologies has been standardized by the German Working Group of Olfactology and Gustology, but there is no agreement about the most suitable imaging modality for diagnosing this disorder.

Material and methods

A total of 24 patients (13 women, 11 men; mean age 52 years) with different types of olfactory dysfunction (anosmia, hyposmia) were examined by objective and subjective olfactometry and magnetic resonance imaging (MRI) of the olfactory bulb.

Results

There was a positive correlation between objective olfactometry and volumetry of the olfactory bulb but no correlation between subjective olfactometry and MRI.

Conclusion

MRI allows an evaluation of the olfactory bulb and appears to be superior to other modalities such as computed tomography (CT). Objective olfactometry remains the gold standard for reliable diagnosis of olfactory dysfunction.     

Superior cerebellar artery infarction in endovascular treatment for tentorial dural arteriovenous fistulas

Background

Superior cerebellar artery (SCA) syndrome shows ipsilateral cerebellar ataxia and Horner's syndrome, contralateral superficial sensory disturbance, as well as nystagmus toward the impaired side, vertigo, and nausea. Occasionally, unilateral lesions may produce bilateral hypogeusia and contralateral hypoacusia.

Objective

To report 2 patients with unilateral lower midbrain ischemic lesions of the inferior colliculus level caused by transarterial embolization for tentorial dural arteriovenous fistulas (TDAVFs).

Methods

Hospital records for 21 patients with TDAVFs mainly treated by endovascular techniques between 2005 and 2008 were reviewed. Two patients with MRI evidence of unilateral SCA territory infarction were investigated.

Results

Of 21 patients, 2 treated transarterially with Onyx-18 (a nonahesive liquid embolic agent) developed infarctions in the territory of SCA. One patient had lateral SCA infarction characterized by ipsilateral gait ataxia, contralateral hemihypoesthesia, with additional ipsilateral ocular motor palsy and bilateral gustatory loss. And the other patient had medial SCA infarction characterized by ipsilateral ataxia contralateral hemihypoesthesia with additional contralateral hypoacusia.

Conclusion

SCA infarction can be caused by transarterial injection of Onyx-18 via SCA or the posterior cerebral artery (PCA) for TDAVFs and additionally presented with gustatory loss and deafness, which is generally not a feature of the SCA syndrome.     

Pseudotumor of the distal common bile duct at endoscopic retrograde cholangiopancreatography

Background

Prior studies have described a pseudocalculus appearance in the distal common bile duct as a normal variant at cholangiography. The objective of this study was to describe the occurrence of pseudotumor in the distal common bile duct at endoscopic retrograde cholangiopancreatography (ERCP).

Methods

Nine patients who underwent ERCP between May 2004 and July 2008 were identified as having a transient eccentric mural-based filling defect in the distal common bile duct. A single reader systematically reviewed all studies and recorded the imaging findings.

Results

The mean diameter of the filling defect was 9 mm (range, 5 to 11). Eight patients had resolution of the filling defect during the same ERCP or on a subsequent ERCP, and in two of these patients the inferior border of the filling defect was not well visualized. The other patient underwent surgical resection of a presumed tumor with no evidence of malignancy on surgical pathology.

Conclusion

An eccentric mural-based filling defect in the distal common bile duct can be artifactual in nature and may reflect transient contraction of the sphincter of Oddi. Recognition of this pseudotumor may help avoid unnecessary surgery.     

Endovascular repair or medical treatment of acute type B aortic dissection? A comparison

Introduction

The aim of this retrospective study was to compare the outcome of thoracic endovascular aortic repair (TEVAR) to that of medical therapy in patients with acute type B aortic dissection (TBD).

Materials and methods

From July 1996 to April 2008, 88 patients presenting with acute TBD underwent either TEVAR (group A, n = 38) or medical therapy (group B, n = 50). Indications for TEVAR were intractable pain, aortic branch compromise resulting in end-organ ischemia, rapid aortic dilatation and rupture. Follow-up was performed postinterventionally, at 3, 6 and 12 months and yearly thereafter and included clinical examinations and computed tomography (CT), as well as aortic diameter measurements and assessment of thrombosis.

Results

Mean follow-up was 33 months in group A and 36 months in group B. The overall mortality rate was 23.7% in group A and 24% in group B, where 4 patients died of late aortic rupture. In group A, complications included 9 endoleaks and 4 retrograde type A dissections, 3 patients were converted to open surgery and 2 needed secondary intervention. None of the patients developed paraplegia. In group B, 4 patients were converted to open surgery and 2 to TEVAR. The maximal aortic diameter increased in both groups. Regarding the extent of thrombosis, our analyses showed slightly better overall results after TEVAR, but they also showed a tendency towards approximation between the two groups during follow-up.

Conclusion

TEVAR is a feasible treatment option in acute TBD. However, several serious complications may occur during and after TEVAR and it should therefore be reserved to patients with life-threatening symptoms.     

Value of CT lymphangiography in the detection of lymphatic leakage: a report of nine cases

Purpose

To demonstrate the value of CT lymphangiography to detect lymphatic leakage, especially at the thoracic level, prior to therapeutic intervention.

Patients and methods

Between 2004 and 2008, nine patients underwent lymphangiography, followed by CT for the evaluation of intractable lymphatic leakage in spite of optimal medical management. Patients included seven females and two males, with age ranging between 25 and 58 years. Lymphangiography was performed after unilateral or bilateral foot injection(s) of Lipiodol ultrafluid followed by standard radiographs of the chest and abdomen and CT of the chest, abdomen and pelvis. The images were reviewed by two experienced radiologists.

Results

Lipiodol leakage was observed in six patients, while three patients showed evidence of lymphangiectasia of the abdominal and/or thoracic lymphatics. Spontaneous resolution of leakage after lymphangiography occurred in three cases.

Conclusion

CT lymphangiography allows direct evaluation of lymphatics, from pelvis to chest, in order to detect the site of leakage at the origin of a chylous effusion and assist in its management.     

Pushable springcoil embolization of pseudoaneurysms caused by gluteal stab injuries

Purpose

To retrospectively review the outcomes of 21 patients with stab wounds to the gluteal region who underwent embolization for pseudoaneurysms causing active bleeding.

Materials and methods

Between 1997 and 2007, 3 superior gluteal artery, 2 inferior gluteal artery and 16 deep femoral artery muscular branch pseudoaneurysms detected by digital subtraction angiography were selectively catheterized with diagnostic catheters with hydrophilic coating and embolized with pushable springcoils. 17 of the 21 pseudoaneurysms were located in a distal end of an artery where outflow vessels could not be depicted. The other 4 lesions were side wall injuries which required the placement of coils distal and proximal to the injury site.

Results

Embolization was successful in controlling the bleeding in all of the patients. 16 patients required 1 or 2 coils, 4 patients required 3 coils and 1 patient required 5 coils. 2 patients had femoral puncture site hematomas which resolved spontaneously. 2 patients required surgical evacuation of large gluteal hematomas following the embolization because of symptoms second to mass effect. There were no procedure related major complications or mortality.

Conclusions

Our experience demonstrates that pushable coil embolization is a relatively simple, effective and economic method for the embolization of pseudoaneurysms caused by penetrating gluteal injuries. Experimenting with other embolization materials does not seem to be justified.     

Congenital portosystemic shunts: Imaging findings and clinical presentations in 11 patients

Objective

To evaluate the clinical anatomy and presentations of congenital portosystemic shunts, and determine features that promote recognition on imaging.

Materials and methods

Institutional review board approval was obtained for this HIPAA-compliant study. The requirement for written informed consent was waived. Radiology reports were retrospectively reviewed from non-cirrhotic patients who underwent imaging studies from January 1999 through February 2009. Clinical sources reviewed included electronic medical records, archived images and histopathological material.

Results

Eleven patients with congenital portosystemic shunts were identified (six male and five female; age range 20 days to 84 years). Seven patients had extrahepatic and four patients had intrahepatic shunts. All 11 patients had absent or hypoplastic intrahepatic portal veins, a feature detected by CT and MRI, but not by US. Seven patients presented with shunt complications and four with presentations unrelated to shunt pathophysiology. Three adult patients had four splenic artery aneurysms. Prospective radiological evaluation of five adult patients with cross-sectional imaging had failed prospectively to recognize the presence of congenital portosystemic shunts on one or more imaging examinations.

Conclusions

Congenital portosystemic shunts are associated with splenic artery aneurysms, a previously unrecognized association. Portosystemic shunts were undetected during prospective radiologic evaluation in the majority of adult patients, highlighting the need to alert radiologists to this congenital anomaly.     

Below knee angioplasty in elderly patients: Predictors of major adverse clinical outcomes

Aim

To determine predictors of clinical outcome following percutaneous transluminal angioplasty (PTA) in elderly patients with below knee atherosclerotic lesions causing intermittent claudication (IC) or critical limb ischaemia (CLI).

Materials and methods

Over 7.5 years, 76 patients (CLI 72%, n = 55) underwent below knee PTA. The composite end-point of interest was major adverse clinical outcome (MACO) of the treated limb at follow-up which was defined as clinical failure, need for subsequent endovascular or surgical revascularization or amputation. Actuarial freedom from MACO was assessed using Kaplan-Meier curves and multivariable Cox proportional hazards regression.

Results

IC was improved in 95% at mean 3.4 years (range 0.5-108 months). Successful limb salvage and ulcer healing were seen in 73% with CLI. Most failures were in the CLI group (27% CLI vs. 5% IC), with an amputation rate of 16% for CLI vs. 5% for IC and persistent ulceration in 24% of CLI. Significant independent predictors of MACO were ulceration (hazard ratio 4.02, 95% CI = 1.55-10.38) and family history of atherosclerosis (hazard ratio 2.53, 95% CI = 1.1-5.92).

Conclusion

Primary below knee PTA is a feasible therapeutic option in this elderly population. Limb ulceration and family history of atherosclerosis may be independent predictors of adverse outcome.     

Time-of-flight MR angiography at 3T versus digital subtraction angiography in the imaging follow-up of 51 intracranial aneurysms treated with coils

Objective

To compare 3D time-of-flight MR angiography (TOF-MRA) at 3 Tesla (3 T) with digital subtraction angiography (DSA) for the evaluation of intracranial aneurysm occlusion after endovascular coiling.

Methods

In a prospective study, 51 consecutive patients (25 females, 26 males; median age, 51 years) with 51 saccular aneurysms treated with endovascular coiling underwent simultaneous DSA and 3 T TOF-MRA at follow-up. DSA and TOF-MRA images were analyzed independently by two senior neuroradiologists. Findings were assigned to 1 of 3 categories in the Raymond classification: complete obliteration, residual neck or residual aneurysm. Agreement between observers and techniques was evaluated using κ statistics.

Results

DSA images were not interpretable for one patient. Interobserver agreement was determined as excellent for DSA (κ = 0.86) and TOF-MRA (κ = 0.80). After reaching a consensus, DSA follow-up showed 26 (51%) complete obliterations, 20 (39%) residual necks and 4 (8%) residual aneurysms. TOF-MRA showed 23 (45%) complete obliterations, 22 (43%) residual necks and 6 (12%) residual aneurysms. Comparison between TOF-MRA and DSA showed excellent agreement between the techniques (κ = 0.86). In the four cases that were misclassified, TOF-MRA findings were assigned to a higher class than for DSA.

Conclusion

TOF-MRA at 3 T is at least as efficient as DSA for the evaluation of intracranial aneurysm occlusion after endovascular treatment with detachable coils. We suggest that TOF-MRA at 3 T might be used as the primary method for imaging follow-up of coiled intracranial aneurysms.     

Motion characterization of aortic wall and intimal flap by ECG-gated CT in patients with chronic B-dissection

Rationale and objectives

To evaluate whether dynamic computed tomography (CT)-imaging can provide functional vessel information in patients with chronic aortic dissection type Stanford-B (ADB).

Materials and methods

In 32 patients, ECG-gated CT-angiography images were obtained. Cross-sectional area change and wall distensibility were investigated by semiautomatic vessel area segmentation at the end of aortic arch. Significance of distensibility differences was tested with regard to the aortic diameter, and the oscillation of the intimal flap was analyzed.

Results

The aorta could be segmented successfully in all patients. These were separated into three subgroups: (A) 6 patients with an aortic diameter <4 cm and without a visible intimal flap, (B) 9 patients with an aortic diameter <4 cm, and (C) 17 individuals with an aortic diameter ≥4 cm; (B) and (C) having a visible intimal flap. Differences in distensibility between the subgroups were not significant. Overall mean distensibility was D_tot = (1.3 ± 0.6) × 10⁻⁵ Pa⁻¹. Analysis of intimal flap oscillation showed a pulsatile short axis diameter decrease of the true lumen of up to 29%.

Conclusion

Dynamic, ECG-gated CT-angiography can demonstrate pulsatile changes in aortic area and a highly variable motion of the intimal flap. Aortic distensibility appears independent of diameter or presence of a intimal flap. Follow-up studies may show correlation with possible complications.     

Long-term follow-up of pyogenic liver abscess by ultrasound

Background/aims

To study the morphology of residual abscess in successfully treated pyogenic liver abscess by ultrasound.

Methods

116 consecutive patients of liver abscess diagnosed from April 2004 to March 2007 were included in this study. Patients with amebic liver abscess were excluded. Patients were treated with antibiotics for 6 weeks and when indicated drained percutaneously. Ultrasound scan was repeated after 2 weeks, 1 month, 3 months, 6 months and 12 months of treatment. Thereafter it was repeated every 6 months.

Results

After exclusion, 102 patients with >150 lesions were studied. Diagnosis was made on the basis of clinical presentation, ultrasound examination and diagnostic aspiration. It was single in 83, double in 12 and more than 2 in seven patients. Size varied from 4.2 cm to 15 cm. Organisms were isolated in 29 patients (E. coli 10, Kliebsiella sp. 6, S. aureus 5, Pseudomonas aeruginosa 2, Acenetobacter 1 and multiple growth 5) in blood and eight patients (E. coli 5 and S. aureus 3 and multiple growth 2) in pus. Majority of abscess resolved sonologically after 2-18 weeks of treatment. Healing was delayed in alcoholic and diabetic patients. In eight patients there was residual abscess even after 104 weeks of follow-up. In four patients it healed with calcification.

Conclusions

Majority of pyogenic liver abscess resolve to normal parenchyma within 18 weeks time. However, some lesions may take longer time to heal even after successful treatment. It should be considered in differential diagnosis of space occupying lesion of the liver in ultrasound and need no therapeutic intervention.