Mutations in TP73 cause impaired mucociliary clearance and lissencephaly.

TP73 belongs to the TP53 family of transcription factors and has therefore been well studied in cancer research. Studies in mice, however, have revealed non-oncogenic activities related to multiciliogenesis. Utilizing whole-exome sequencing analysis in a cohort of individuals with a mucociliary clearance disorder and cortical malformation, we identified homozygous loss-of-function variants in TP73 in seven individuals from five unrelated families. All affected individuals exhibit a chronic airway disease as well as a brain malformation consistent with lissencephaly. We performed high-speed video microscopy, immunofluorescence analyses, and transmission electron microscopy in respiratory epithelial cells after spheroid or air liquid interface culture to analyze ciliary function, ciliary length, and number of multiciliated cells (MCCs). The respiratory epithelial cells studied display reduced ciliary length and basal bodies mislocalized within the cytoplasm. The number of MCCs is severely reduced, consistent with a reduced number of cells expressing the transcription factors crucial for multiciliogenesis (FOXJ1, RFX2). Our data demonstrate that autosomal-recessive deleterious variants in the TP53 family member TP73 cause a mucociliary clearance disorder due to a defect in MCC differentiation.

Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in type 1 diabetes and type 2 diabetes: Lipid goal attainment in a large German-Austrian diabetes registry.

AIM: To assess the implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline recommendations for lipid-lowering therapies among more than 30 000 patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) in a German and Austrian registry from 2020 to 2022. MATERIALS AND METHODS: Registry data from 2020 and 2021 of 32 170 adult patients (8314 patients with T1D and 23 856 with T2D) were stratified according to the 2019 ESC/EAS risk categories, and guideline-based low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goal attainment was analysed. RESULTS: In patients with T1D (median age 38.35 [20.51-57.13] years), overall statin use was 19.3%, ezetimibe use was 2.2% and the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors or fibrates was less than 1%. In patients with T2D (median age 68.76 [58.86-78.39] years), 45.7% received statins, 3.4% received ezetimibe, and fibrates and PCSK9 inhibitors were used by 1% and 0.1%, respectively. Among patients with T1D, 6.16% reached their risk-based recommended LDL-C goal of less than 55 mg/dL (very high risk), 10.97% of less than 70 mg/dL (high risk), and 69.50% of less than 100 mg/dL (moderate risk), respectively. In patients with T2D, 11.81% reached their risk-based goal of LDL-C less than 55 mg/dL, 16.25% of less than 70 mg/dL, and 51.33% of less than 100 mg/dL. Non-HDL-C goals were reached more often, with 15.3%, 25.52% and 91.61% in patients with T1D and 18.56%, 17.96% and 82.30% in patients with T2D for very high, high and moderate risk, respectively. CONCLUSION: Approximately 2 years after publication of the guidelines, LDL-C and non-HDL-C goal attainment was rarely achieved in patients with T1D and T2D with a high or very high cardiovascular risk.

Guidelines adherence in the prevention and management of chronic kidney disease in patients with diabetes mellitus on the background of recent European recommendations - a registry-based analysis.

BACKGROUND: Recent European Society of Cardiology (ESC)/European Association for the Study of Diabetes (EASD) guidelines provide recommendations for detecting and treating chronic kidney disease (CKD) in diabetic patients. We compared clinical practice with guidelines to determine areas for improvement. METHODS: German database analysis of 675,628 patients with type 1 or type 2 diabetes, with 134,395 included in this analysis. Data were compared with ESC/EASD recommendations. RESULTS: This analysis included 17,649 and 116,747 patients with type 1 and type 2 diabetes, respectively. The analysis showed that 44.1 and 49.1 % patients with type 1 and type 2 diabetes, respectively, were annually screened for CKD. Despite anti-diabetic treatment, only 27.2 % patients with type 1 and 43.5 % patients with type 2 achieved a target HbA1c of < 7.0 %. Use of sodium-glucose transport protein 2 inhibitors (1.5 % type 1/8.7 % type 2 diabetes) and glucagon-like peptide-1 receptor agonists (0.6 % type 1/5.2 % type 2 diabetes) was limited. Hypertension was controlled according to guidelines in 41.1 and 67.7 % patients aged 18-65 years with type 1 and 2 diabetes, respectively, (62.4 vs. 68.4 % in patients > 65 years). Renin angiotensin aldosterone inhibitors were used in 24.0 and 40.9 % patients with type 1 diabetes (micro- vs. macroalbuminuria) and 39.9 and 47.7 %, respectively, in type 2 diabetes. CONCLUSIONS: Data indicate there is room for improvement in caring for diabetic patients with respect to renal disease diagnosis and treatment. While specific and potentially clinically justified reasons for non-compliance exist, the data may serve well for a critical appraisal of clinical practice decisions.

Renal function deterioration in adult patients with type-2 diabetes.

BACKGROUND: To explore, in a large group of patients with type-2 diabetes (T2DM), renal function decline in terms of the slope of the estimated glomerular filtration rate (eGFR) over time, and to find out how classical risk factors, such as the presence of hypertension, dyslipidemia and microalbuminuria, affect the renal function. METHODS: The analysis included 32,492 adult T2DM patients from the DIVE/DPV registries who had serial eGFR determinations and information on the presence of microalbuminuria, hypertension and dyslipidemia available. RESULTS: Patients had a mean age of 66.3 years, 52.6% were male with a mean BMI of 31.7 kg/m2. The mean eGFR was 78.4 ± 21.4 mL/min/1.73m2. The results showed that the prevalence of renal function impairment understood as chronic kidney disease (CKD) is considerable (53.0%) in a population of patients with T2DM and has a high incidence rate of 6.6% within a year. Serial determinations of the eGFR are, however, infrequent (7.8% of all patients) and these patients are characterised by the presence of a high-risk profile for CKD, such as hypertension (88.1%) and dyslipidemia (66.1%). Over a three-year time period, 30.9% of the patients had an eGFR slope of -12 mL/min/1.73m2 or more; and more than a doubled proportion of patients with an eGFR < 30 mL/min/1.73 m2 (3.8% vs. 1.8%; p < 0.001). Hypertension and albuminuria contributed to renal function decline while dyslipidemia did not negatively affect the slope. CONCLUSION: CKD is highly prevalent in patients with T2DM. Serial surveillance of the glomerular filtration rate is, however, not established in clinical practice, which would be necessary as indicated by a doubling of patients with an eGFR < 30 mL/min/1.73 m2 within 3 years. Moreover, the use of renin-angiotensin blocking agents was low, pointing at considerable room for improvement. Taken together we conclude that a closer surveillance of patients with diabetes based on the presence of further risk factors is mandatory combined with a mandatory prescription of RAS blocking agents once microalbuminuria and / or renal function deterioration develops.

Patient and disease characteristics of type-2 diabetes patients with or without chronic kidney disease: an analysis of the German DPV and DIVE databases.

BACKGROUND: To evaluate the characteristics of type 2 diabetes (T2DM) patients with or without chronic kidney disease (CKD) in Germany. METHODS: Using combined DPV/DIVE registry data, the analysis included patients with T2DM at least ≥ 18 years old who had an estimated glomerular filtration rate (eGFR) value available. CKD was defined as an eGFR < 60 mL/min/1.73 m2 or eGFR ≥ 60 mL/min/1.73 m2 and albuminuria (≥ 30 mg/g). Median values of the most recent treatment year per patient are reported. RESULTS: Among 343,675 patients with T2DM 171,930 had CKD. Patients with CKD had a median eGFR of 48.9 mL/min/1.73 m2 and 51.2% had a urinary albumin level ≥ 30 mg/g. They were older, had a longer diabetes duration and a higher proportion was females compared to patients without CKD (all p < 0.001). More than half of CKD patients (53.5%) were receiving long-acting insulin-based therapy versus around 39.1% of those without (p < 0.001). CKD patients also had a higher rate of hypertension (79.4% vs 72.0%; p < 0.001). The most common antihypertensive drugs among CKD patients were renin-angiotensin-aldosteron system inhibitors (angiotensin converting enzyme inhibitors 33.8%, angiotensin receptor blockers 14.2%) and diuretics (40.2%). CKD patients had a higher rate of dyslipidemia (88.4% vs 86.3%) with higher triglyceride levels (157.9 vs 151.0 mg/dL) and lower HDL-C levels (men: 40.0 vs 42.0 mg/dL; women: 46.4 vs 50.0 mg/dL) (all p < 0.001) and a higher rate of hyperkalemia (> 5.5 mmol/L: 3.7% vs. 1.0%). Comorbidities were more common among CKD patients (p < 0.001). CONCLUSION: The results illustrate the prevalence and morbidity burden associated with diabetic kidney disease in patients with T2DM in Germany. The data call for more attention to the presence of chronic kidney disease in patients with diabetes, should trigger intensified risk factor control up and beyond the control of blood glucose and HbA1c in these patients. They may also serve as a trigger for future investigations into this patient population asking for new treatment options to be developed.

Early-onset leukoencephalopathy due to a homozygous missense mutation in the DARS2 gene.

Mutations in the DARS2 gene are known to cause leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL), a rare autosomal recessive neurological disorder. It was originally described as juvenile-onset slowly progressive ataxia and spasticity, but recent reports suggest a broader clinical spectrum. Most patients were found to carry compound heterozygous DARS2 mutations, and only very few patients with homozygous mutations have been described so far. We present here an 8-month-old boy carrying a homozygous missense mutation in DARS2 who clinically showed severe neurological deterioration after a respiratory tract infection, followed by an almost complete remission of symptoms. This report further extends the knowledge about the clinical and molecular genetic spectrum of LBSL.

Long survival in Leigh syndrome: new cases and review of literature.

Leigh syndrome (MIM 25600), also known as infantile subacute necrotizing encephalomyelopathy, is a neurodegenerative disorder with characteristic bilateral symmetric lesions in basal ganglia and subcortical brain regions. It is commonly associated with systemic cytochrome c oxidase (COX) deficiency and mutations in the SURF1 gene (MIM 185620), encoding a putative assembly or maintenance factor of COX. The clinical course is dominated by neurodevelopmental regression, brain stem, and basal ganglia involvement (e.g., dystonia, apnea) with death often occurring before the age of 10 years. Herein, we present three sisters carrying a previously reported homozygous SURF1 mutation (c.868_869insT) that is predicted to result in a truncated protein with loss of function. Our patients show heterogeneous clinical findings with different distribution patterns of metabolic lesions in brain magnetic resonance imaging (MRI) as well as a Chiari malformation with hydrocephalus in one patient. However, all three siblings show an unusual long survival (12 years and>16 years). COX activity was not detectable in one patient and strongly reduced in the other two. We discuss these findings with respect to a review of the literature. A total of 15 additional patients with survival>14 years have been reported so far. Overall, no clear genotype-phenotype correlations are detectable among these patients.

Canavan's spongiform leukodystrophy (Aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature.

Canavan disease (CD; MIM 271,900) or spongy degeneration of the central nervous system (CNS) is a lethal, rare autosomal recessive leukodystrophy, first described in 1931 (Canavan in Arch Neurol Psychiatry 25: 299-308, 1931). The clinical presentation includes severe neurologic impairment and macrocephaly with onset of symptoms at the age of 3-5 months. Biochemical and genetic fundamentals of the disease are elucidated. Imaging diagnosis is principally based on MRI with important role of MR spectroscopy. We report the cerebral sonographic findings in a severely affected infant with CD: Diffuse hyperechogenicity and small multicystic changes of white matter as well as an inverted pattern of echogenicity between cortical gray and subcortical white matter. These findings are compared to to the few cases found in literature and to normal ultrasound examples. Finally, ultrasound and MRI imaging findings are correlated.

Multidetector-CT angiography in pulmonary embolism-can image parameters predict clinical outcome?

OBJECTIVE: To assess if pulmonary CT angiography (CTA) can predict outcome in patients with pulmonary embolism (PE). METHODS: Retrospective analysis of CTA studies of patients with PE and documentation of pulmonary artery (PA)/aorta ratio, right ventricular (RV)/left ventricular (LV) ratio, superior vena cava (SVC) diameter, pulmonary obstruction index (POI), ventricular septal bowing (VSB), venous contrast reflux (VCR), pulmonary infarction and pleural effusion. Furthermore, duration of total hospital stay, necessity for/duration of ICU therapy, necessity for mechanical ventilation and mortality were recorded. Comparison was performed by logistic/linear regression analysis with significance at 5%. RESULTS: 152 patients were investigated. Mean duration of hospital stay was 21 ± 24 days. 66 patients were admitted to the ICU; 20 received mechanical ventilation. Mean duration of ICU therapy was 3 ± 8 days. Mortality rate was 8%. Significant positive associations of POI, VCR and pulmonary infarction with necessity for ICU therapy were shown. VCR was significantly associated with necessity for mechanical ventilation and duration of ICU treatment. Pleural effusions were significantly associated with duration of total hospital stay whereas the RV/LV ratio correlated with mortality. CONCLUSION: Selected CTA findings showed significant associations with the clinical course of PE and may thus be used as predictive parameters.

Rhizomelia and Impaired Linear Growth in a Girl with Juvenile Paget Disease: The Natural History of the Condition.

In ultra-rare bone diseases, information on growth during childhood is sparse. Juvenile Paget disease (JPD) is an ultra-rare disease, characterized by loss of function of osteoprotegerin (OPG). OPG inhibits osteoclast activation via the receptor activator of nuclear factor-κB (RANK) pathway. In JPD, overactive osteoclasts result in inflammatory-like bone disease due to grossly elevated bone resorption. Knowledge on the natural history of JPD, including final height and growth, is limited. Most affected children receive long-term antiresorptive treatment, mostly with bisphosphonates, to contain bone resorption, which may affect growth. In this study, we report the follow-up of height, growth velocity, and skeletal maturation in a 16-year-old female patient with JPD. The patient was treated with cyclic doses of pamidronate starting at 2.5 years of age and with 2 doses of denosumab at the age of 8 years, when pamidronate was paused. In the following years, a sustainable decline in a height z-score and a stunted pubertal growth spurt; despite appropriate maturation of the epiphyseal plates of the left hand, the proximal right humerus and both femora were observed. Whether this reflects the growth pattern in JPD or might be associated to the antiresorptive treatments is unclear, since there is very limited information available on the effect of bisphosphonates and denosumab on growth and the growth plate in pediatric patients. Studies are needed to understand the natural history of an ultra-rare bone disease and to assess the effects of antiresorptive treatment on the growing skeleton.

Cumulative effective dose associated with radiography and CT of adolescents with spinal injuries.

OBJECTIVE: The purpose of this study was to analyze the quantity and distribution of cumulative effective doses in diagnostic imaging of adolescents with spinal injuries. MATERIAL AND METHODS: At a level 1 trauma center from July 2003 through June 2009, imaging procedures during initial evaluation and hospitalization and after discharge of all patients 10-20 years old with spinal fractures were retrospectively analyzed. The cumulative effective doses for all imaging studies were calculated, and the doses to patients with spinal injuries who had multiple traumatic injuries were compared with the doses to patients with spinal injuries but without multiple injuries. The significance level was set at 5%. RESULTS: Imaging studies of 72 patients (32 with multiple injuries; average age, 17.5 years) entailed a median cumulative effective dose of 18.89 mSv. Patients with multiple injuries had a significantly higher total cumulative effective dose (29.70 versus 10.86 mSv, p < 0.001) mainly owing to the significantly higher CT-related cumulative effective dose to multiple injury patients during the initial evaluation (18.39 versus 2.83 mSv, p < 0.001). Overall, CT accounted for 86% of the total cumulative effective dose. CONCLUSION: Adolescents with spinal injuries receive a cumulative effective dose equal to that of adult trauma patients and nearly three times that of pediatric trauma patients. Areas of focus in lowering cumulative effective dose should be appropriate initial estimation of trauma severity and careful selection of CT scan parameters.

MRI in lipid-lowering agent-associated myopathy: a retrospective review of 21 cases.

OBJECTIVE: The objective of our study was to identify disease-specific patterns of myopathic changes in patients with lipid-lowering agent (LLA)-associated myopathy using a dedicated MRI protocol. MATERIALS AND METHODS: Axial T1- and T2-weighted STIR images were obtained for the detection of lipomatosis and edema, respectively, of the thighs and legs. Information about patient age, sex, duration of dyslipidemia and of medication use, latency of symptom onset, maximum creatine kinase (CK) level, presence of myalgia and muscle weakness, and LLA or LLAs used was collected. RESULTS: Significant correlations resulted for the radiologic diagnosis of LLA-associated myopathy and maximum CK level; the presence of edema and maximum CK level; edema and weakness in the ventral thigh muscle group, thigh adductors, or deep dorsal muscle group of the legs; and lipomatosis and weakness of the deep dorsal muscle group of the legs and peroneal muscle group, respectively. CONCLUSION: MRI is a method that helps detect active pathologic processes in patients with suspected LLA-associated myopathy but does not reveal disease-specific patterns.

Growth plate fractures of the distal tibia: is CT imaging necessary?

PURPOSE: Comparison of conventional radiographs (CR) of distal tibial growth plate fractures [Salter-Harris (SH) fracture types I-V/triplane fractures I-III] with computed tomography (CT) as the reference standard and assessment of diagnostic benefit of CT imaging in the affected patients. MATERIALS AND METHODS: We retrospectively evaluated all growth plate injuries of the distal tibia with complete pre-therapeutic imaging material (CR and CT including MPR) obtained between August 2001 and December 2006. The imaging material was randomised and presented to two radiologists. Fracture of metaphysis, epiphysis and epiphyseal line were noted separately for distal tibia. In case of fracture, involvement of the articular surface, articular dehiscence and ridge formation, subluxation and number of tibial fragments were evaluated. All fractures were classified as SH type I-V or triplane fractures type I-III. Sensitivity, specificity, positive and negative predictive value and overall accuracy of CR were compared to CT. RESULTS: Thirty-three patients (mean age 14 ± 2 years) were evaluated. CR showed significantly less tibial fragments as compared to CT (1.39 ± 0.75 vs. 1.61 ± 1.25; p = 0.023). The overall accuracy of CR was <90% for fracture involving the metaphysis (82%), dehiscence of the articular surface (64%), ridge formation of the articular surface (61%) and subluxation (79%). The CR evaluation showed differing SH classification in CT in 10/33 cases (30%) with the highest misclassification rates in type-III SH fracture. For evaluation of triplane fractures, CR classification was incorrect in five cases (71%) out of seven. No misclassification occurred in types I and II SH fractures. CONCLUSION: The CR of distal tibial growth plate fractures showed a low overall accuracy for articular surface dehiscence, articular ridge formation and subluxation as compared to CT. CT revealed significantly more fragments. It is difficult to correctly classify type III/IV SH fractures and triplane fractures with CR thus emphasising the necessity of using CT in selected patients.

Which labral lesion can be best reduced with external rotation of the shoulder after a first-time traumatic anterior shoulder dislocation?

INTRODUCTION: Immobilization in external rotation after a first-time traumatic anterior shoulder dislocation has been shown to improve the position of the labroligamentous lesion relative to the glenoid rim. The purpose of the present study was to evaluate the effect of the external rotation position of the shoulder on different types of labroligamentous lesions in patients with first-time traumatic anterior shoulder dislocation by using MRI. PATIENTS AND METHODS: We performed a standardized MRI in internal and external rotation of the shoulder after initial reduction in 34 patients with a first-time traumatic anterior shoulder dislocation. Labroligamentous lesions were classified as Bankart, Perthes, or nonclassifiable. Four distinct grades were used to classify the amount of plastic deformation of the anterior labroligamentous structures. The position of the labrum was defined relative to the tip of the glenoid rim by measuring the dislocation and separation. RESULTS: In all patients, dislocation and separation of the labrum relative to the rim of the glenoid were significantly improved in shoulders in the external rotation position compared to those in the internal rotation position. We observed 15 Bankart, 15 Perthes, and 4 non-classifiable lesions. No HAGL or GLAD lesions were found. Fourteen patients showed a plastic deformation grade I, 16 showed grade II, 3 showed grade III, and 1 showed grade IV. In regression analysis, the odds ratio was 1.100 for the type of lesion and 1.660 for the grade of plastic deformation. Perthes lesions (with an intact anterior scapular periosteum) and grade I plastic deformations showed the best labral reduction on the external rotation MRI. CONCLUSION: Placing the shoulder in external rotation after a first-time traumatic shoulder dislocation, significantly improves the position of the labroligamentous lesion on the glenoid rim. Perthes lesions that showed a low grade of plastic deformation displayed better reduction in external rotation and then compared to Bankart or other lesions that showed a high grade of plastic deformation. In conclusion, immobilization of the shoulder after a first-time traumatic shoulder dislocation is most effective in patients with Perthes lesions that show low grade plastic deformation.

CT angiography in suspected pulmonary embolism: impact of patient characteristics and different venous lines on vessel enhancement and image quality.

OBJECTIVE: The objective of our study was to compare image quality, patient characteristics, and different catheters in pulmonary CT angiography (CTA) performed with bolus tracking and z-axis automated tube current modulation (ATCM) in patients with suspected pulmonary embolism. SUBJECTS AND METHODS: One hundred twenty-six patients were referred to undergo pulmonary CTA with bolus tracking and ATCM. Besides patient characteristics, the type, position, size, and side of venous catheters were documented. Pulmonary vessel enhancement and image noise were quantified; signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Subjective vessel contrast was assessed by two radiologists in consensus. RESULTS: Patient age showed a moderate but significant positive correlation to vessel enhancement (r = 0.244, p = 0.006), CNR (r = 0.178, p = 0.046), and subjective image quality (r = 0.344, p < 0.001). Patient weight revealed a significant negative correlation to vessel enhancement (r = -0.496, p < 0.001), SNR (r = -0.446, p < 0.001), CNR (r = -0.425, p < 0.001), and subjective image quality (r = -0.422, p < 0.001). In univariate analysis, SNR and CNR were significantly higher in patients who received contrast medium through peripheral catheters (30 +/- 13 and 27 +/- 13, respectively) than in those in whom central catheters were used (22 +/- 8 and 19 +/- 7, p = 0.041 and p = 0.029, respectively). Neither patient sex nor catheter size, position, or side had any significant impact on image quality. CONCLUSION: Patient age and weight showed significant impact on vascular attenuation and image quality in pulmonary CTA with bolus tracking and ATCM, whereas patient sex and different peripheral catheters did not significantly influence image parameters.

Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients.

Mutations in the filamin C gene (FLNC) cause a myofibrillar myopathy (MFM), morphologically characterized by focal myofibrillar destruction and abnormal accumulation of several proteins within skeletal muscle fibres. We studied 31 patients from four German families to evaluate the phenotype of filaminopathy. All patients harboured the same p.W2710X mutation in FLNC. Haplotype analysis suggested a founder mutation in these German filaminopathy families. The mean age at onset of clinical symptoms was 44 +/- 6 years (range, 24-57 years). Slowly progressive muscle weakness was mostly pronounced proximally, initially affecting the lower extremities and involving the upper extremities in the course of disease progression, similar to the distribution of weakness seen in limb-girdle muscular dystrophies (LGMD). Patients frequently developed respiratory muscle weakness. About one-third of the patients showed cardiac abnormalities comprising conduction blocks, tachycardia, diastolic dysfunction and left ventricular hypertrophy indicating a cardiac involvement in filaminopathy. Serum creatine kinase levels varied from normal up to 10-fold of the upper limit. Magnetic resonance imaging studies showed a rather homogenous pattern of muscle involvement in the lower extremities differing from that in other types of MFM. Myopathological features included perturbation of myofibrillar alignment, accumulation of granulofilamentous material similar to that seen in primary desminopathies and abnormal intracellular protein deposits typical of MFM. Decreased activities of oxidative enzymes and fibre hypertrophy seem to be early features, whereas dystrophic changes were present in advanced stages of filaminopathy. Rimmed vacuoles were detected in only a few cases. The intracellular aggregates were composed of a variety of proteins including filamin C, desmin, myotilin, Xin, dystrophin and sarcoglycans. Therapy is so far limited to symptomatic treatment. The German filaminopathy cohort, the largest group of patients studied so far, shares phenotypic features with LGMD and presents with characteristic histopathological findings of MFM.

Effectiveness of CT-guided percutaneous biopsies of the spine: an analysis of 202 examinations.

RATIONALE AND OBJECTIVES: The study goal was to retrospectively evaluate the effectiveness of computed tomography (CT)-guided spinal biopsies. MATERIAL AND METHODS: Two hundred two CT-guided vertebral biopsies performed between May 1999 and June 2004 in 187 patients were retrospectively analyzed. Patient characteristics (age, sex, antibiotic therapy), technical parameters (depth and number of biopsies, needle approach), lesion features (spinal level, osteolysis, fluid collections, soft tissue tumor), and complications were documented. Furthermore, histopathological and microbiological diagnoses were considered. RESULTS: There were two focal hematomas in our study group (complication rate: 1%). Histopathological diagnosis was established in 74% of examinations with spondylitis (41% of cases) being most common. In spinal tumors (27% of cases), malignant lesions were found in 52 of 54 examinations (96%). Osteolysis was diagnosed in 98% of patients with spondylitis and in 87% of patients with tumors (P < .01). Spinal tumors were most commonly seen in the sacrum (53%, P < .001), whereas spondylitis typically occurred in the lumbar spine (55%, P = .001). Neither patient age nor sex, needle approach, needle depth, or vertebral abnormalities showed a significant impact on diagnostic accuracy. Microbiological tests were performed in 98 patients (49%); 62 of 98 patients (65%) received antibiotic therapy. In 12 of 62 patients (19%) with antibiotic therapy and in 9 of 36 patients (25%) without antibiotic treatment, microbiological tests were positive (P = .153). Staphylococcus aureus was found in 9 of 21 examinations (43%). CONCLUSIONS: CT-guided vertebral biopsy is a safe and effective procedure to establish final diagnosis in spinal lesions of unclear origin. Patient characteristics, lesions features, and technical considerations did not influence sample quality. In spondylitis, which was commonly caused by Staphylococcus aureus, microbiological yield was low regardless of antibiotic therapy.

Computed tomography-navigated transthoracic core biopsy of pulmonary lesions: which factors affect diagnostic yield and complication rates?

RATIONALE AND OBJECTIVES: Only a few studies have systematically evaluated risk factors for pneumothorax and pulmonary hemorrhage in computed tomographically (CT)-guided transthoracic lung biopsy (TLB). We evaluated the diagnostic yield of CT-guided TLB and determined risk factors for pneumothorax and hemorrhage. METHODS: One hundred seventy-two CT-guided TLBs were performed on 159 patients (mean age 66 +/- 11 years; 72% male) using a 16-gauge core biopsy needle. Lesion and patient characteristics, lung function analysis, CT signs of emphysema, histopathologic diagnoses, and complications were recorded. Statistical analysis was performed with multivariate regression analysis. RESULTS: Histopathologic diagnosis was established in 153 cases (89%). Although lesion size was higher (47 +/- 29 vs. 43 +/- 35 mm, P = .191) and depth was lower (22 +/- 23 vs. 6 +/- 23 mm, P = .350) in procedures with histopathologic diagnosis, no parameter showed significant impact on diagnostic yield. Sensitivity and specificity for detection of malignancy were 93% and 100%, respectively, whereas positive and negative predictive values were 100% and 88%. Overall accuracy was 95%. Pneumothorax occurred in 45 procedures (26%). Hemorrhage was recorded in 17 procedures (10%). There was higher frequency of pneumothorax in smaller lesions (35 +/- 23 vs. 50 +/- 31 mm, P = .003; odds ratio = .96) and greater depth (29 +/- 29 vs. 20 +/- 19 mm, P = .05; odds ratio = 1.03). CT signs of emphysema revealed higher incidence of hemorrhage (35% vs. 23%; P = .04; odds ratio=41.03). Other parameters were nonsignificant. CONCLUSIONS: The high diagnostic yield of CT-guided TLB was not affected by lesion characteristics or emphysema. Pneumothorax rate was influenced by lesion size and depth. Hemorrhage was associated with CT signs of emphysema.

Structural and Functional Lung Impairment in Primary Ciliary Dyskinesia. Assessment with Magnetic Resonance Imaging and Multiple Breath Washout in Comparison to Spirometry.

RATIONALE: Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by heterogeneous airway disease. Traditional lung function techniques (e.g., spirometry) may underestimate severity and complexity of PCD. OBJECTIVES: We assessed lung impairment in individuals with PCD using structural and functional magnetic resonance imaging (MRI) and different lung function techniques. METHODS: A total of 30 study participants with PCD (median, 13.4 yr; range, 5-28 yr) underwent structural and functional MRI, spirometry, and multiple breath washout (MBW) on the same day. Primary endpoints included structural MRI morphology scores, relative ventilation, and perfusion impairment from functional MRI, forced expiratory volume in 1 second (FEV1) from spirometry, and lung clearance index (LCI) from MBW. RESULTS: Severity and complexity of PCD lung disease varied significantly between individuals. Structural lung disease was detected in all subjects with a median (interquartile range) extent score of 10.3 (7-19; maximum score = 60). Functional MRI ventilation impairment was present in 52% of subjects, affecting 24.2% (21.1 to 25.2%) of the lung. Relative perfusion impairment was detected in 78% of individuals affecting 21.1% (19.4 to 25.9%) of the lung. LCI was abnormal in 83% (median, 8.3 [2.6 to 13.2] z-scores) and FEV1 was abnormal in 27% (-0.5 [-1.6 to 0.3] z-scores) of individuals. Concordance between spirometry and imaging outcomes was poor, with 52% of patients showing both abnormal MRI and LCI values, but normal FEV1. CONCLUSIONS: Discordance between lung function and imaging outcomes in patients with PCD supports the use of both imaging and lung function, such as MBW, for surveillance of this heterogeneous disease.

Unilateral hyperplasia of a cervical spinous process as a rare congenital variant of the spine.

Congenital variants of the cervical spine may mimic traumatic lesions and may cause recurrent episodes of pain. We report a 24-year-old female patient with chronic neck pain who had marked unilateral hyperplasia of the spinous process of the seventh cervical vertebra. CT and MRI clearly depicted the abnormality and, furthermore, ruled out posttraumatic spinal changes. To our knowledge, our case is the first patient reported with this rare congenital variant diagnosed by cross-sectional imaging.