Martin C. Freund

Epidemiology and outcome of infections due to Aspergillus terreus: 10-year single centre experience.

Aspergillus terreus, a less common pathogen, appears to be an emerging cause of infection at our institution, the Medical University Hospital of Innsbruck. Thus the epidemiology and outcome of A. terreus infections over the past 10 years was assessed. We analysed 67 cases of proven invasive aspergillosis (IA) according to the European Organisation for Research and Treatment of Cancer/Mycoses Study Group criteria, investigated antifungal susceptibility of amphotericin B (AMB), voriconazole and caspofungin and performed molecular typing of A. terreus. Patients with proven IA caused by A. terreus (n = 32) and non‐A. terreus (n = 35) were evaluated. The two groups were comparable in terms of age, gender, underlying disease, antifungal prophylaxis and duration of neutropenia (P > 0·05). Leukaemia was the most common underlying malignancy. Fungal dissemination occurred in 63% of the patients. Aspergillus terreus infections were associated with a lower response rate to AMB therapy (20%), compared with 47% for patients with non‐A. terreus infections (P < 0·05). In vitro, A. terreus was found to be resistant to AMB and molecular typing discriminated between patients isolates, showing a high strain diversity with 26 distinct types (I‐XXVI) identified by combination of three primers. Aspergillus terreus infections displayed evidence of AMB resistance in vitro and in vivo and were associated with a high rate of dissemination and poor outcome; A. terreus causes systemic infections of endemic character in Tyrol, Austria. The onset of A. terreus infection depends not on the degree of immunosuppression but on environmental Aspergillus spp. exposure.

Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma

Patients with small hepatocellular carcinoma (HCC) can be cured by liver transplantation (LT). However, many patients drop out during the waiting time as a result of tumor progression. We prospectively investigated the effect of transarterial chemoembolization on long‐term survival of 116 patients with HCC listed for LT. Intention‐to‐treat analysis revealed that patients with either complete or partial response to therapy (no vital tumor or devascularization of ≥30%, respectively) as assessed by computed tomographic scan before LT had far better 1‐, 2‐, and 5‐year survival rates (100, 93.2, and 85.7%; and 93.8, 83.6, and 66.2%, respectively) compared with those with no response or with tumor progression (82.4, 50.7, and 19.3%). Posttransplant survival analysis showed a marked survival benefit according to transarterial chemoembolization response: patients with complete or partial response had 1‐, 2‐, and 5‐year survival rates of 89.1, 85.1, and 85.1%, and 88.6, 77.4, and 63.9%, respectively, compared with 68.6, 51.4, and 51.4% for patients whose disease did not respond to therapy. Subgroup analysis, however, showed that these benefits were only seen in patients whose disease met the Milan criteria, but not in disease exceeding the Milan criteria but fitting the expanded University of California at San Francisco criteria. These patients were also more likely to drop out as a result of tumor progression while waiting for LT (dropout rate 12.1 vs. 2.9%) and to develop recurrent HCC (21.6 vs. 7.6%). Downstaged patients did even worse, with a dropout rate of 26.7% and a 5‐year survival rate of only 25%. In conclusion, the response to preoperative chemoembolization may predict long‐term outcome after LT. Liver Transpl 13:272–279, 2007.

Bone bruise of the knee Histology and cryosections in 5 cases

We evaluated the histopathologic and cryosectional appearance of bone bruise injuries of the knee detected on MRI. Histologic evaluation of bone biopsies from 3 patients revealed microfractures of cancellous bone, edema and bleeding in the fatty marrow. Between intact lamellar bone trabecules, fragments of hyaline cartilage mixed with highly fragmented bone trabecules were found. Postmortem specimens were obtained from 2 more patients, killed in motor vehicle accidents. MRI revealed bone bruise injuries of the lateral femoral condyle and of the lateral tibial plateau in 1 knee and anterior cruciate ligament disruption, a medial meniscus tear and bone bruise injury of the tibial plateau and of the lateral femoral condyle in the other specimen. The specimens were embedded in physiologic saline solution and frozen to -30 degrees C. By rotationcryotomy, 1 mm slices were removed from the surface of the specimens and documented on photographs. Subchondral lesions and bleeding were found, corresponding to the MR images.

The Value of Computed Tomography-Guided Percutaneous Lung Biopsy for Diagnosis of Invasive Fungal Infection in Immunocompromised Patients

We assessed Calcofluor white staining, Aspergillus polymerase chain reaction, and a galactomannan enzyme immunoassay for diagnosis of fungal infection with use of computed tomography-guided percutaneous lung biopsy specimens obtained from 61 patients. The sensitivity and specificity of computerized tomography, Aspergillus polymerase chain reaction, and galactomannan enzyme immunoassay were 100% and 50%, 100% and 86%, and 88% and 94%, respectively.

Diagnosing Invasive Aspergillosis during Antifungal Therapy by PCR Analysis of Blood Samples

ABSTRACT We evaluated the value of Aspergillus PCR as a tool for diagnosing invasive aspergillosis from whole-blood samples during antifungal therapy. In a 3-year study, 36 patients receiving antifungal therapy due to chest radiographic findings highly suggestive of fungal pneumonia were evaluated. The PCR results from whole-blood samples were compared to those obtained from bronchoalveolar lavage fluids and/or tissue specimens. A total of 205 whole-blood samples, 15 fine-needle aspirations or tissue biopsy specimens, and 21 bronchoalveolar lavage fluids and tracheal secretions were analyzed using PCR. Of the 36 patients, 15 had proven, 9 had probable, and 12 had possible invasive Aspergillus infection according to European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions. For patients with proven infection the sensitivity values of PCR in lung and blood samples were 100 and 40%, respectively. The negative predictive value of blood monitoring under conditions of antifungal treatment was 44%. Clearance of fungal DNA from blood was associated with resolution of clinical symptoms in six of nine patients with proven infection. Repeated positive PCR results for Aspergillus were associated with fatal outcome, as three of six patients died. For patients with probable infection the sensitivity values of PCR in lung fluid and blood were 66 and 44%, respectively. The benefit of PCR diagnosis using whole-blood samples is limited when sampling takes place after treatment has been started. Performance of Aspergillus PCR using tissue samples is recommended in addition to microscopic examination and culture technique for sensitive detection of fungal infection.

Ultrasound Guidance for Facet Joint Injections in the Lumbar Spine: A Computed Tomography-controlled Feasibility Study

We conducted this study to develop an ultrasound-guided approach for facet joint injections of the lumbar spine. Five zygapophyseal joints (L1-S1) on each side of 5 embalmed cadavers were examined by ultrasound for a total of 50 examinations. The joint space was demonstrated under ultrasound guidance. The midpoint of the joint space, defined as the middle of its cranio-caudal extension on its dorsal surface, was taken as a reference point, and its position was computed from its depth and lateral distance from the spinous process. Forty-two of 50 approaches could be clearly visualized. Subsequently, these distances were compared to those obtained by computed tomography (CT). To assess the efficacy of ultrasound in the needle placement, all lumbar facet joints were approached in one embalmed cadaver. The exact placement of the needle tips was again evaluated by CT. Ultrasound and CT measurements showed the same mean depth and lateral distance to the reference point, 3.15 ± 0.5 cm and 1.9 ± 0.6 cm, respectively. Pearson’s coefficient of correlation was 0.86 (P < 0.0001) between ultrasound and CT. All 10 needle tips were within the joint space during simulated facet joint injections. We conclude that ultrasound guidance might be a useful adjunct for facet joint injections in the lumbar spine.

Real-time sonographic imaging for periradicular injections in the lumbar spine: a sonographic anatomic study of a new technique.

We conducted this study to develop a sonographically guided approach to the spinal nerve of the lumbar spine and to assess its feasibility and accuracy by means of computed tomography (CT).

Ultrasound-guided facet joint injections in the middle to lower cervical spine: a CT-controlled sonoanatomic study.

ObjectivesThe aim of this study was to investigate the efficacy of ultrasound as a guiding tool for simulated cervical facet joint injections in cadavers. MethodsA total of 40 ultrasound examinations at 5 levels (C6-7 to C2-3) were performed on 4 embalmed cadavers. The zygapophyseal joints were located with ultrasound. First, the transverse processes of C6 and C7 were established and the facet joint of C6-7 was demonstrated. The midpoint of this joint space, defined as the middle of its cranio-caudal extension on its lateral surface, was taken as a reference point. Ipsilateral distances (A, B, C, and D) between this point and each one of the 4 facet joints of the cervical spine up to the facet joints C2-3 were then computed. Subsequently, coronal computed tomography (CT) scans were taken to verify these distances. In a second experiment, a spinal needle was advanced under ultrasound guidance to the zygapophyseal joints from C2-3 to C6-7 on both sides of 1 cadaver. The exact placement of the needle tips was again verified by CT. ResultsIn 4 attempts, a depiction of the joint space was not possible. Ultrasound and CT provided the same mean measurements of 1.2±0.2 cm, 2.0±0.3 cm, 3.0±0.2, and 4.0±0.5 cm for distances A, B, C, and D, respectively. All 10 needle tips were located in the joint space during simulated facet joint injections, as also verified by CT. DiscussionThis preclinical study suggests that ultrasound is a useful guiding tool for facet joint injections in the cervical spine.

Sensitivity of lung clearance index and chest computed tomography in early cf lung disease

It is widely accepted that CF lung disease starts before clinical symptoms become apparent or spirometry deteriorates. Computed chest tomography (CT) is the reference method for identifying structural changes in CF; however, radiation exposure limits its use as a monitoring tool. It has been suggested that the Lung Clearance Index (LCI) measured by Multiple Breath Washout (MBW) for assessing ventilation inhomogeneity is a more sensitive surrogate marker than spirometry allowing non-invasive monitoring of CF lung disease. The aim of this study was to prospectively investigate the diagnostic accuracy of the LCI in comparison to CT in CF patients with early lung disease and normal FEV(1) (>80% pred.). MBW and ultra-low-dose CT were performed in 34 patients (6-26 years). LCI was abnormal in 76.5% subjects. LCI and CT correlated significantly in 82.3%. LCI was related to presence and extent of structural lung changes observed on CT with a sensitivity of 88%. Diagnostic accuracy of the LCI for detecting CF lung disease in patients with normal FEV(1) was good when compared to CT. Results indicate that structural changes are unlikely if a normal LCI is measured. We speculate that serial measurements of the LCI for assessing ventilation inhomogeneity may help to identify early structural lung disease and help to reduce the individual cumulative radiation dose. The LCI may be a suitable surrogate marker for monitoring progression of CF lung disease and effect of treatment in both, clinical care and research settings.

Ultrasound-guided periradicular injections in the middle to lower cervical spine : An imaging study of a new approach

Background and Objectives The objective of this study was to show the efficacy of ultrasound in facilitating the performance of a simulated cervical periradicular injection in cadavers. Methods A total of 40 ultrasound-guided examinations at 4 levels (C3 to C7) were performed on 4 embalmed cadavers. The cervical spinal nerves were located with ultrasound. First, the transverse process of each level was taken as a sonoanatomic landmark. The most lateral aspect of the transverse process of the seventh cervical vertebra was then established as the reference point. Ipsilateral distances (A, B, C, and D) between this point and each one of the transverse processes of the cervical spine up to the third vertebra were then computed. Subsequently, coronal computed tomography (CT) scans were taken to verify these distances. In a second part, a spinal needle was advanced under ultrasound guidance to the spinal nerves C5 to C8 on both sides of one cadaver. The exact placement of the needle tips was checked by CT. Results The transverse processes were identified in all cadavers. In 5 attempts, a depiction of the spinal nerves was not possible. Ultrasound and CT provided the same mean measurements of 1.1 cm, 2.1 cm, 3.1 cm, and 4.1 cm for distances A, B, C, and D, respectively. All 8 needle tips were placed within 5 mm dorsal to the spinal nerve and less than 5 mm away from the posterior tubercle of each levels transverse process, as also verified by CT. Conclusions This preclinical study suggests that ultrasound is a useful guiding tool for periradicular injections in the cervical spine.