Characteristic Radiographic Changes Research Articles

Stereotactic Radiosurgery (SRS) for Large Brain Metastases: Dosimetric and Clinical Predictors of Local Progression and Radionecrosis

Stereotactic radiosurgery (SRS) provides high rates of local control for small brain metastases with low rates of radionecrosis (RN). Larger targets are associated with increased risk of both local progression (LP) and RN. In this analysis, we hypothesized that dosimetric and clinical parameters predict for risk of LP and RN in SRS targets larger than two centimeters. We retrospectively reviewed patients with one or more targets with either an intact versus post-operative cavity larger than 2.0 cm treated with LINAC-based SRS between 2017 and 2022 at one institution. We assessed for association between patient, treatment, and disease variables with LP and RN. Variables assessed included tumor resection status, PDL1 positivity, target volume, maximum and minimum target dose, EQD2 and BED (a/b = 2 for necrosis and a/b = 10 for tumor control), as well as receipt of steroids, bevacizumab, or systemic therapy before or after SRS. Radionecrosis was determined by characteristic radiographic changes. Analyses were performed for the entire cohort and within subsets including by resection status and dose fractionation. A total of 178 lesions in 143 patients were included. Targets with volume diameters measuring at least 2 cm were used. Median follow-up was 2.3 years. Overall survival at 1 and 2 years was 56% and 32%, respectively. Most lesions (n = 119) were resected and treated with SRS post-operatively. The most common dose and fractionation schemes used were 30 Gy in 5 fractions (n = 89) and 27 Gy in 3 fractions (n = 63). For the entire cohort, the cumulative incidence of LP 1 and 2 years was 26% and 34%, respectively. The cumulative incidence of radiographic radionecrosis at 1 and 2 years was 12% and 17%, respectively. There was no difference in LP or RN between 27 Gy in 3 fractions versus 30 Gy in 5 fractions (p>0.5 for both). Median planning target volume (PTV) size was 18.5 cc for the 27 Gy in 3 fraction group compared to 21.9 cc in the 30 Gy in 5 fraction group. Minimum or maximum dose within the target was not associated with increased risk of LP or RN. Among patients receiving 27 Gy in 3 fractions, patients treated with resection followed by SRS had lower risk of LP compared to those treated with SRS alone (HR: 0.15, 95% CI: 0.03-0.64, p = 0.011). Among patients receiving 30 Gy in 5 fractions, patients who received corticosteroids prior to SRS had a lower risk of RN (HR: 0.14, 95% CI: 0.03-0.66, p = 0.013). For the entire cohort as well as within all subgroups, PD-L1≥1% was associated with increased risk of RN (p<0.001 for all). Selecting the optimal SRS dose fractionation and planning parameters to minimize both LP and RN remains a challenge for large targets. In this analysis, 27 Gy in 3 fractions appeared to provide equivalent LP and RN compared to 30 Gy in 5 fractions, and may be more convenient for patients. Patients with PD-L1≥1% with large brain targets treated with SRS may be at increased risk of RN; corticosteroid prophylaxis may be considered in this population.

A Holistic Approach to Bone Tumors in Dogs and Cats: Radiographic and Histologic Correlation.

The skeletal system is a common site for neoplasia in dogs and cats, and primary bone tumors may develop from any of the mesenchymal tissues present in bone. Imaging and histopathology are routinely used in the diagnosis of bone tumors, and the 2 techniques are highly complementary. While imaging may be highly suggestive of a specific diagnosis and treatment may be instituted based on this, definitive diagnosis requires histopathology of either incisional or excisional biopsies or an amputation specimen. However, there are a number of diagnostic dilemmas when the pathologist interprets bone biopsy samples, such as distinguishing reactive bone and tumor bone, fracture callus and tumor bone, different benign fibro-osseous lesions, and different types of bone sarcoma. This review outlines the characteristic radiographic and histologic changes associated with these diagnostic problems to aid in resolving them. When a holistic approach is taken to evaluation of the signalment, history, and clinical, radiologic, and microscopic features, a diagnosis may be possible. The pathologist is greatly assisted in the interpretation of bone samples by having access to imaging and should routinely request either the images or the imaging reports if they are not received from submitting veterinarians.

Scurvy in children: Down but not out

Background: Scurvy, a common disease of the past, has become rare in the modern era. Because of lack of awareness regarding its clinical and radiological manifestations, diagnosis of scurvy is often missed or delayed resulting in unnecessary and potentially harmful diagnostic and therapeutic interventions. Dermatological manifestations are a very important component of the clinical picture and can suggest the diagnosis to the unsuspecting physicians. The objectives were to describe the clinical presentation of scurvy in children in the modern era and to highlight its dermatological manifestations. Methods: This was a retrospective chart review of children diagnosed with scurvy over a period of 10 years at a tertiary care hospital. Results: Eleven children, 6 girls and 5 boys, aged from 21 months to 16 years with scurvy were identified. All the children had an underlying disorder that predisposed them to scurvy, with cerebral palsy in 10 and autism spectrum disorder with celiac disease in one child. All had presented with musculoskeletal complaints of irritability, limb pain, painful restriction of movements, and in some cases, swelling of the affected limb. Dermatological signs consisting of various combinations of perifollicular hyperkeratosis and hemorrhages, petechiae, ecchymosis, corkscrew hair, and bleeding gums were present in 10 children. Characteristic radiographic changes were seen in all the 8 children who underwent this examination. All children responded dramatically to treatment with oral Vitamin C. Conclusions: Awareness of clinical and radiographic signs of scurvy allows early diagnosis and treatment of scurvy. Dermatological manifestations are the most noticeable and helpful clues to the diagnosis of scurvy.

Viral Therapy for Glioblastoma

Viral Therapy for Glioblastoma

Risk factors of metabolic bone disease of prematurity

ObjectiveTo identify the factors that increase risk of metabolic bone disease of prematurity (MBD). Study designA retrospective case-control study of infants born between January 2013–April 2014 with gestation age <30weeks and birth weight <1000g. MBD was defined as serum alkaline phosphatase above 500U/L and characteristic radiographic changes. Information was obtained on the presence of specific comorbidities. ResultsOf 76 infants evaluated, 40 met criteria for MBD. Median gestational age was 25weeks in both groups (p=0.512). Median birth weight of infants with MBD was significantly lower than that of controls (560 vs. 765g, p<0.01). Longer period of parenteral nutrition and dexamethasone use was observed in MBD group. Cholestasis was associated with the highest likelihood of MBD (OR 16.6, 95% CI 4.8–56.9). Seizures (OR 5.2, 95% CI 1.3–20.5) and the prolonged use of diuretics (OR 2.6, 95% CI 1.0–7.0) also significantly increased the likelihood of MBD. Only cholestasis remained significant (OR 9.6, 95% CI 2.1–45.3) after multiple regression analysis. ConclusionCholestasis is a significant risk factor for the development of MBD. Our future studies will be directed towards determining the causal relationship between cholestasis and MBD.

Early characteristic radiographic changes in mucolipidosis II.

Although mucolipidosis type II has similar metabolic abnormalities to those found in all the mucopolysaccharidoses and mucolipidoses, there are distinctive diagnostic radiographic changes of mucolipidosis II in the perinatal/newborn/infant period. To describe the early characteristic radiographic changes of mucolipidosis II and to document when these changes manifest and resolve. We retrospectively reviewed radiographs and clinical records of 19 cases of mucolipidosis II from the International Skeletal Dysplasia Registry (1971-present; fetal age to 2½ years). A radiologist with special expertise in skeletal dysplasias evaluated the radiographs. The most common abnormalities were increased vertebral body height (80%, nonspecific), talocalcaneal stippling (86%), periosteal cloaking (74%) and vertebral body rounding (50%). Unreported findings included sacrococcygeal sclerosis (54%) and vertebral body sclerosis (13%). Rickets and hyperparathyroidism-like (pseudohyperparathyroidism) changes (rarely reported) were found in 33% of cases. These changes invariably started in the newborn period and resolved by 1year of age. The conversion from these early infantile radiographic features to dysostosis multiplex changes occurred in 41% of cases, and within the first year after birth. Several findings strongly suggest the diagnosis of mucolipidosis II, including cloaking in combination with one or more of the following radiographic criteria: talocalcaneal stippling, sacrococcygeal or generalized vertebral body sclerosis, vertebral body rounding, or rickets/hyperparathyroidism-like changes in the perinatal/newborn/infancy period. These findings are not found in the other two forms of mucolipidosis nor in any of the mucopolysaccharidoses.

Milwaukee Shoulder Syndrome

Milwaukee shoulder syndrome (MSS) is a rare destructive, calcium phosphate crystalline arthropathy. It encompasses an effusion that is noninflammatory with numerous aggregates of calcium hydroxyapatite crystals in the synovial fluid, associated with rotator cuff defects. We describe a patient that presented with recurrent shoulder pain and swelling with characteristic radiographic changes and MSS was confirmed on aspiration of the synovial fluid.

A retrospective study of digital subtraction technique to detect sclerotic changes in alveolar bone on intraoral radiographs of bisphosphonate-treated patients

Several reports have suggested that sclerotic changes in cancellous bone of the jaw and thickening of the lamina dura are characteristic radiographic changes of an early silent stage of bisphosphonate (BP)-related osteonecrosis of the jaw. No quantitative evaluation has been reported to support this hypothesis. Emago® software (Oral Diagnostic Systems, Amsterdam, Netherlands) can perform digital subtraction on intraoral radiographs even if they were obtained by non-standardized radiography, provided the dimensional error is within a certain limit. The purpose of this study was to evaluate whether sclerotic changes of alveolar bone or thickening of lamina dura in patients using BP can be detected using the subtraction function of Emago. The authors selected 46 pairs of intraoral radiographs of the mandibular molar area in dental patients. All radiographs were obtained at intervals of 6 months or more. Among the 46 pairs, 7 pairs were from patients who were being treated with BP (study subjects), and 39 pairs were from patients who had not been using BP (controls). All pairs of radiographs underwent digital subtraction by Emago. The number of pixels of the sclerotic areas was counted and compared between subjects and controls. The sclerotic changes were significantly distinguishable in two of the seven subjects (28.6%) using BP. Digital subtraction function of Emago was able to detect sclerotic changes in alveolar bone. Therefore, it is suggested that the subtraction function of Emago is a useful tool for quantitatively detecting sclerotic changes that are observed at an early, silent stage of BP-related osteonecrosis of the jaw.

Pulmonary Care and Adjunctive Therapies for Prevention and Amelioration of Bronchopulmonary Dysplasia

Shortly after the introduction of assisted ventilation in the newborn, bronchopulmonary dysplasia (BPD) was first described. Northway and coworkers described a group of preterm infants who developed chronic respiratory failure and characteristic radiographic changes after prolonged mechanical ventilation. The prevention and management of BPD in infants at risk is challenging due to the complex pathogenesis of multiple contributing factors that include prematurity, supplemental oxygen exposure, mechanical ventilation, patent ductus arterious, inflammation, genetic predisposition and postnatal infection. Treatment of existing BPD requires a coordinated approach including optimal nutrition, careful fluid management, evidence-based drug therapy, and gentle respiratory techniques aimed at minimizing lung injury. The best respiratory support strategy remains unclear and requires further investigation but includes avoidance of ventilator-induced lung injury (barotraumas and volutrauma), hyperoxemia, and hypocapnea. Among the available interventions antenatal steroids, caffeine, and surfactant have the best risk-benefit profile. Systemic postnatal corticosteroids should be used only in ventilated infants unable to be weaned from the ventilator. Quality improvement techniques may have a role towards improvement of hospital systems geared toward reduction of BPD.

Retrospective case–control study of the effects of long-term dosing with meloxicam on renal function in aged cats with degenerative joint disease

Medical records (2005-2009) of a feline-only practice were searched for cats with degenerative joint disease (DJD) treated using meloxicam. DJD was diagnosed by the presence of at least two of the following: (i) altered mobility (observed by the owner), (ii) abnormal physical findings, (iii) characteristic radiographic changes. The primary study cohort consisted of cats older than 7 years that had received meloxicam for variable intervals in excess of 6 months, and for which complete records were available. These cats were subdivided according to whether detectable chronic kidney disease (CKD) was present ('renal group'), or not ('non-renal group'), and, for the 'renal group', according to the cat's IRIS category. Serum biochemistry, urinalysis (including urine specific gravity [USG]), body mass and condition score were monitored regularly. Progression of CKD in the 'renal group' and 'non-renal group' of cats was compared to two groups of age- and IRIS-matched control cats not receiving meloxicam (from the same clinic, over the same time period). The study was thus a case-control design, with two study groups. Thirty-eight cats with DJD receiving long-term meloxicam therapy met the inclusion criteria. Of these, 22 cats had stable CKD at the start of treatment (stage 1, eight cats; stage 2, 13 cats; stage 3, one cat). No cats initially had an elevated urinary protein to creatinine ratio. The remaining 16 cats initially had normal renal analytes and adequately concentrated urine. The median age of the 'renal' and 'non-renal' meloxicam groups was 15.5 and 13.4 years, respectively. The median treatment duration was 467 days in the 'renal group' and 327 days in the 'non-renal group'. After titration (to the lowest effective dose), the median maintenance dose was 0.02 mg/kg/day in both groups (range 0.015-0.033 mg/kg/day). There was no difference in sequential serum creatinine concentration or USG measurements between the 'non-renal group' treated with meloxicam compared to control cats not treated with meloxicam. There was less progression of renal disease in the 'renal group' treated with meloxicam compared to the age- and IRIS-matched cats with CKD not given meloxicam. These results suggest that a long-term maintenance dose of 0.02 mg/kg of meloxicam can be safely administered to cats older than 7 years even if they have CKD, provided their overall clinical status is stable. Long-term meloxicam therapy may slow the progression of renal disease in some cats suffering from both CKD and DJD. Prospective studies are required to confirm these findings.

Rapidly progressive destructive arthritis in psoriatic arthritis sine psoriasis: do bone resorption marker levels predict outcome of bone destruction in psoriatic arthritis?

(2011). Rapidly progressive destructive arthritis in psoriatic arthritis sine psoriasis: do bone resorption marker levels predict outcome of bone destruction in psoriatic arthritis? Modern Rheumatology: Vol. 21, No. 1, pp. 106-108.

Acute Neuropathic Joint Disease

Charcot neuroarthropathy, or, as it is also known, neuropathic joint disease (NJD), is a particularly severe form of osteoarthritis. It is recognized by severe joint damage in the context of relatively little pain in the presence of neuropathy and associated with characteristic radiographic changes in well-established disease. Patients with diabetes are at particular risk of NJD; permanent disability through foot deformity or amputation as a consequence of peripheral neuropathy (1) and diabetes is now the leading cause of NJD. The midfoot or ankle joints are most commonly affected in diabetic patients (2). The limited epidemiologic data on NJD suggest that ∼0.1–0.4% of patients with diabetes develop NJD (3), usually 10–15 years after the onset of diabetes, and up to 16% of diabetic patients with peripheral neuropathy have been reported to be affected by NJD (4), which therefore represents a considerable cause of diabetic ankle- and foot-related morbidity. NJD often presents acutely, resulting in misdiagnosis and inappropriate treatment and consequently leading to disastrous damage and possible loss of the affected limb (3). Typically, in the acute phase, NJD presents as a warm, edematous, and erythematous joint (5,6). As a result of sensory neuropathy, there may be little pain or tenderness, and the patient may not even seek medical assistance. During examination, a bounding pedal pulse compared with the other limb is found (7). The radiographic changes of chronic NJD include florid new bone formation, joint space loss, and severe joint destruction and deformity, but these characteristic changes are usually absent in early NJD. In this clinical context, cellulitis, osteomyelitis, or infection may be diagnosed instead and treated accordingly, and the window of opportunity for the initiation of treatment designed to minimize subsequent NJD joint …

Vitamin D-dependent rickets type 2 with characteristic radiographic changes in a 4-month-old kitten

This report describes the presenting signs, biochemical abnormalities, and radiographic changes in a 4-month-old kitten with vitamin D-dependent rickets type 2. Details of therapy are described and possible reasons for treatment failure are discussed.

The sedlin gene for spondyloepiphyseal dysplasia tarda escapes X-inactivation and contains a non-canonical splice site

Mutations in the sedlin gene cause spondyloepiphyseal dysplasia tarda (SEDT), a rare X-linked chondrodysplasia. Affected males suffer short stature, deformation of the spine and hips, and deterioration of intervertebral discs with characteristic radiographic changes in the vertebrae. We have sequenced two full-length cDNA clones corresponding to the human sedlin gene. The longest cDNA is 2836 bp, containing a 218 bp 5′ untranslated region, a 423 bp coding region, and a 2195 bp 3′ untranslated region. The second cDNA does not contain exon 2, suggesting alternative splicing. Sedlin was finely mapped in Xp22.2 by Southern blot analysis on a yeast artificial chromosome/bacterial artificial chromosome map. Comparison of the cDNA sequence and genomic sequence identified six sedlin exons of 67, 142, 112, 147, 84, and 2259 bp. The corresponding introns vary in size from 339 to 14,061 bp. Splice site sequences for four of the five introns conform to the GT/AG consensus sequences, however, the splice site between exons 4 and 5 displays a rare non-canonical splice site sequence, AT/AC. Northern blot analysis showed expression of the sedlin gene in all human adult and fetal tissues tested, with the highest levels in kidney, heart, skeletal muscle, liver, and placenta. Four mRNA sizes were detected with the major band being 3 kb and minor bands of 5, 1.6, and 0.9 kb (the smallest product may reflect a sedlin pseudogene). Sedlin is expressed from both the active and the inactive human X chromosomes helping to explain the recessive nature and consistent presentation of the disease. Human sedlin shows homology to a yeast gene, which conditions endoplasmic reticulum/golgi transport. Characterization of the human sedlin cDNA and determination of the sedlin gene structure enable functional studies of sedlin and elucidation of the pathogenesis of SEDT.

Onset of Erosive Osteoarthritis in a Teenage Girl

Erosive osteoarthritis is a disorder that predominantly affects the hands of postmenopausal or middle aged women. Ages usually range from 30 to 83 years. Although the etiology of erosive osteoarthritis is not known, a lack of estrogen hormones has been implicated in the pathogenesis. We report a patient with onset of symptoms at age 16 and a diagnosis at age 21. She has aggressive inflammatory involvement of the distal interphalangeal joints and characteristic radiographic changes with central erosions. She is not postmenopausal nor does she have any conditions that are believed to be possible associations with erosive osteoarthritis. To the best of our knowledge, this is the youngest reported patient with erosive osteoarthritis in the literature.

Vitamin A deficiency and severe bronchopulmonary dysplasia in very low birthweight infants.

Preterm infants often have abnormally low serum vitamin A concentrations. Persistence of vitamin A deficiency for a prolonged postnatal period may contribute to the development of bronchopulmonary dysplasia. We retrospectively analyzed data from 22 infants with birthweight < or = 1250 g who had hyaline membrane disease requiring mechanical ventilation with oxygen and in whom serum vitamin A concentrations had been measured at the onset of enteral feeding and every 2 weeks thereafter. Thirteen infants (low serum vitamin A group) had one or more serum vitamin A concentrations < or = 11 mcg/dL at > 10 days of age. In 9 infants (higher serum vitamin A group) all serum vitamin A concentrations were > 11 mcg/dL at > 10 days of age. Mean birthweight, mean gestational age, sex, race, incidence of antenatal maternal glucocorticoid treatment and ventilatory support on the first day of life were similar for the two groups. Severe bronchopulmonary dysplasia was as defined as characteristic radiographic changes and either discharge from the hospital with supplemental oxygen or death from respiratory failure at > 28 days of age following mechanical ventilation with oxygen since birth. The incidence of severe bronchopulmonary dysplasia was significantly higher in the low serum vitamin A group (11/13, 3 deaths vs. 1/9, no deaths; p=0.001). The incidence of pulmonary air leak, the number of ventilator days, the number of days of postnatal glucocorticoid treatment for chronic lung disease, the number of episodes of suspected sepsis and the number of days of antibiotic treatment also were higher in the low serum vitamin A group. Low serum vitamin A group infants were older at the onset of enteral feeding (21 days vs. 8 days; p = 0.001) and during feeding their average daily enteral intake of vitamin A was lower (713 IU vs. 1255 IU; p = 0.001) when compared with infants in the higher serum vitamin A group. Our retrospective analysis of data from these infants confirms earlier reports from other workers that persistent marked vitamin A deficiency in very low birthweight infants is associated with a high incidence of severe bronchopulmonary dysplasia, delayed onset of enteral feeding and low enteral intake of vitamin A.

IDIOPATHIC PULMONARY FIBROSIS

IPF is a distinct clinicopathologic entity. Despite controversies concerning histopathologic classification, characteristic physical findings, radiographic changes, and physiologic abnormalities together with histopathology are diagnostic of IPF. Recent allowances in the investigation of the alveolitis have suggested therapeutic interventions that target pathogenic mechanisms. Current experience supports anti-inflammatory therapy for the alveolitis associated with IPF; however, the appropriate assessment of disease activity and therapy remain controversial.

Cyclosporine-associated central neurotoxicity after heart transplantation

Cyclosporine central neurotoxicity has been described after bone marrow, kidney, and liver transplantation but has not been well documented after heart transplantation. This case illustrates severe reversible neurotoxicity after heart transplantation with characteristic radiographic changes in magnetic resonance imaging.

Paget's disease of bone

Paget's disease of bone is a common disorder of older patients that may sometimes cause a variety of signs and symptoms referable to the skeleton. An intrinsic bone-remodeling abnormality in this disease may lead to bone deformity, pain, and various arthritic or neurologic complications. Characteristic radiographic changes can be seen, and typically the serum alkaline phosphatase level and total urinary hydroxyproline excretion are elevated. Current therapies that interfere with excess osteoclast activity are helpful in many cases, but treatment choices and expected responses must be considered in the context of the individual patient.

Progressive Diaphyseal Dysplasia Presenting as Neuromuscular Disease

Two children with progressive diaphyseal dysplasia (Engelmann's disease) were initially diagnosed as having a neuromuscular disorder because of their clinical presentations of muscle weakness, a waddling gait, and limb pain. Radiographs revealed the characteristic radiographic changes.