Chemokine receptor CXCR4 based positron emission tomography imaging in systemic sclerosis-related interstitial lung disease.

OBJECTIVE: To assess chemokine receptor CXCR4 expression in lung parenchyma and on peripheral immune cells in systemic sclerosis-related interstitial lung disease (SSc-ILD) patients. METHODS: SSc-ILD patients underwent 68Ga- CPCR4 Trifluoroacetate positron emission tomography (PET) scan, SUVmean in different lung regions and architecturally abnormal areas, and receiver operating characteristic (ROC) curves were analyzed. CXCR4 expression on peripheral immune cells using flow cytometer was studied and correlated with the different lung regions. In addition, subset analysis of CXCR4 expression by clinical subset (early, progressive, stable), ILD pattern and anti-Scl-70 positivity were done. RESULTS: On PET, SSc-ILD patients showed higher median SUVmean uptake of CXCR4 in the whole lung (0.56; p< 0.0001), different lung regions and architecturally abnormal areas than controls. Highest area under curve (AUC) were observed in dorsobasal regions (AUC-0.91; p< 0.0001) and reticular with architecturally distorted areas (AUC-0.95; p< 0.0001). Progressive subset had higher whole lung median SUVmean (0.73) than early (0.49; p< 0.0001) and stable (0.45; p< 0.0001) subsets, and AUC than early and stable subsets. Usual interstitial pneumonia pattern ILD showed higher CXCR4 uptake compared with non-specific interstitial pneumonia (p= 0.0032). Additionally, a trend for higher uptake was noted in anti-Scl70 positive patients as compared with anti-Scl70 negative ones. SSc-ILD patients had higher CD4+CXCR4+T cells (p= 0.0003), and CD8+CXCR4+T cells (p= 0.0013), and showed moderate to strong association on correlation with the lung parenchymal regions. CONCLUSION: In SSc-ILD, CXCR4 expression is upregulated in both lung parenchyma and peripheral T cells, significantly in progressive and UIP subsets. CXCR4 expression is a potential tool for activity assessment and prognostication.

MDCT evaluation of distal radius fractures and their association with carpal and distal ulnar fractures.

PURPOSE: The purpose of this study was to evaluate the characteristics of distal radius fractures (DRFs) in patients undergoing multi-detector computed tomography (MDCT) and their association with carpal and distal ulnar fractures. METHODS: This retrospective study analyzed 120 patients, who underwent MDCT for evaluation of DRFs. Two radiologists independently evaluated the data for various fracture characteristics and for associated carpal and distal ulnar fractures. RESULTS: Out of 120 DRFs, 74 were complete articular, 40 were partial articular and only 6 were extra-articular. Displacement was present in 99 fractures and intra-articular step off was present in 73 fractures. A total of 81 carpal bone fractures were identified in 46 (38.3%) patients, with more than one carpal bone fracture in 21 patients. Distal ulnar fractures were detected in 79 patients (65.8%), out of which 67 involved the ulnar styloid. DRFs with intra-articular step off were more frequently associated with carpal bone fracture (p value: 0.021), while displaced DRFs were more frequently associated with distal ulnar fracture (p value <0.001). Interobserver agreement for detection of carpal bone fractures (κ = 0.807) and distal ulnar fractures (κ = 0.923) was excellent. CONCLUSION: Majority of DRFs in patients referred for MDCT were complete articular with high incidence of displacement and intra-articular step off. Associated carpal bone and distal ulna fractures were not uncommon.

Role of Shear Wave Elastography of Synovium to Differentiate Rheumatoid and Tubercular Arthritis.

Background: Synovitis is the underlying pathology in various arthritis, and sometimes, it is difficult to differentiate various arthritis clinically or even by imaging. The purpose of our study was to use shear wave elastography (SWE) to evaluate rheumatoid arthritis (RA) and tubercular (TB) arthritis and to differentiate them using synovial stiffness. Methods: The prospective study was performed on Supersonic Imagine Aixplorer Ultrasound (USG) machine using a linear array probe SL10-2 (2-10 MHz). A total of 29 participants, 15 of RA (ACR/EULAR criteria) and 14 of proven TB arthritis were included. Region of interest of 1 mm was applied on the hypertrophied synovium and quantitative SWE data in form of elasticity (kPa) and velocity (m/s) were measured. Discrete categorical data were presented as n (%). Mean values were recorded along with standard deviation and the range of values. To find a maximal cutoff value of elasticity and velocity - receiver operating characteristic curve were plotted. Results: The mean elasticity and velocity values were 54.81 ± 10.6 kPa and 4.2 m/s ± 0.42 for RA and 37 ± 10 kPa and 3.4 ± 0.47 m/s for TB group. Significant difference (P < 0.001) was seen in elastic modulus values between rheumatoid and TB group with cutoff of 43.6 kPa to differentiate the two groups (sensitivity - 86.7% and specificity - 80%). Similar significant (P < 0.001) results were seen with velocity values, with cutoff of 3.76 m/s (sensitivity - 86.7% and specificity - 80%). Conclusion: SWE shows the potential to be a useful adjunct to gray scale and color Doppler USG in differentiating various arthritis on the basis of elastic properties of the synovium. Elastic modulus and velocity are useful SWE quantitative parameters for synovial evaluation and can differentiate RA and TB arthritis.

The role of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging for the diagnosis of diabetic foot osteomyelitis: a preliminary report.

Purpose: To assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusionweighted imaging (DWI) in diagnosing diabetic foot osteomyelitis (DFO). Material and methods: Twenty-five participants with suspected osteomyelitis were included, who underwent MRI including DCE-MRI and DWI sequences. It was subsequently followed by bone biopsy and microbiological analysis (gold standard). The participants were divided into 2 groups based on biopsy results: DFO-positive or DFO-negative. The semi-quantitative DCE-MRI parameters (SI0, SImax, SIrel, wash-in rate [WIR], and type of curve) and apparent diffusion coefficient (ADC) values were subsequently compared between the 2 groups. Results: Out of the 25 cases, 19 were DFO-positive and 6 were DFO-negative on bone biopsy. The SI0, SImax, and WIR were significantly higher in DFO-positive cases (p-value 0.050, 0.023, and 0.004, respectively). No difference was seen in SIrel. 100% negative cases revealed type-I curve, and 94% of positive cases showed type-II curve. SI0 > 143.4 revealed a sensitivity of 94.7% and specificity of 83.3%. SImax had a sensitivity of 89.5% but lower specificity of 67.7% at a cut-off value of 408.35. The most significant difference was seen with WIR; p-value ~0.004. At the cut-off value of > 1.280, it had a specificity and sensitivity of 100% and 76%, respectively. Also, ADC values below 1.57 × 10-3 had a sensitivity of 88.2% and specificity of 80% for diagnosing DFO. Conclusions: DWI and DCE-MRI provide non-invasive sequences, which can help to increase the overall specificity and sensitivity of conventional MRI for the diagnosis of osteomyelitis, differentiating it from acute Charcot's arthropathy.

Effect of mycophenolate mofetil (MMF) on systemic sclerosis-related interstitial lung disease with mildly impaired lung function: a double-blind, placebo-controlled, randomized trial.

The efficacy and safety of mycophenolate mofetil (MMF) has been studied in patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD) with moderate-severe impairment. There is no study on its use in patients with mildly impaired lung function. The objective of this study is to determine the efficacy and safety of MMF for treating mild SSc-ILD (forced vital capacity (FVC) ≥ 70% predicted). This was a double-blind, randomized, placebo-controlled pilot trial. The subjects with SSc-ILD with FVC ≥ 70% were randomized to receive either MMF (2 g/day) or placebo for 6 months. FVC, diffusing capacity of lungs for carbon monoxide (DLCO), modified Rodnan skin score (mRSS), Short Form-36 (SF36v2), Mahler's Dyspnoea Index (MDI), and 6-min walk distance (6MWD) were recorded at baseline and at 6 months. Forty-one subjects were included in the study (MMF: 20, placebo: 21). FVC decreased by a median of 2.7% (range - 21 to 9) in MMF arm and increased by 1% (range - 6 to 10) in placebo arm (p = 0.131). SF36v2 scores improved in both the groups. Median change in MDI (3 vs 3), DLCO (1% vs 1.5%), and 6MWD (0 m vs 0 m) was similar between the study groups. MMF was effective in improving mRSS (- 5 vs - 1, p = 0.045) compared to placebo. Adverse events occurred with similar frequency in both the study groups. In this pilot study, MMF did not result in significant improvement in lung function in SSc-ILD with minimally impaired lung function, but was effective in reducing the skin tightness. Larger studies are needed to confirm these findings. This study was registered at ClinicalTrials.gov (NCT02896205).

MRI in shoulder arthropathies: A short review.

Arthropathies are a frequent cause of shoulder pain and comprise of a wide range of clinical entities that may pose a diagnostic challenge. Though history and clinical examination remain vital, imaging plays a pivotal role in accurate diagnosis. Magnetic resonance imaging (MRI) remains an invaluable tool for imaging evaluation of shoulder involvement by various arthropathies. With attention to characteristic imaging features, radiologist may be able to differentiate between various disease processes affecting the shoulder joint. In this article, we have provided a brief review of common and uncommon MRI manifestations of various arthropathies affecting the shoulder joint.

Randomized controlled trial of pre-transplant zoledronate versus observation for prevention of bone loss in allogeneic hematopoietic cell transplantation.

Background: Approximately half of allogeneic hematopoietic cell transplantation (HCT) recipients experience significant bone loss in the early post-HCT period. Only recently have international guidelines started recommending early screening. However, the guidance for intervention remains conservative. In this study, we sought to evaluate the efficacy of pre-transplant prophylactic zoledronate in preventing early bone loss in allogeneic HCT recipients. Methods: This was an open-label, investigator-initiated, phase 2 randomized controlled trial (RCT) of prophylactic zoledronate versus observation to prevent bone loss in allogeneic HCT recipients. Recipients aged ≥ 18 years of age were included after informed consent and randomized to prophylactic zoledronate 4 mg pre-HCT or observation in a 1:1 ratio. The primary outcome of the study was bone mineral density (BMD) loss at the femoral neck (FN), total hip (TH), and lumbar spine (LS), as assessed using dual-energy X-ray absorptiometry (DXA) on day+100 post-HCT. The secondary outcomes included BMD loss on day+365 and Z scores on day+100 and day+365 at the FN, TH, and LS sites. Results: The trial was terminated because the interim analysis showed a significant benefit in the intervention arm, with 50% planned recruitment. A total of 40 patients were randomized to the zoledronate and control arms. Both arms were matched for age, sex, diagnosis, pre-HCT steroid exposure, body mass index, human leukocyte antigen (HLA) match, and conditioning intensity. The grade 2-4 acute graft versus host disease (GVHD) incidences were comparable. The primary endpoint of BMD loss at FN and TH at day+100 was significant (5.62% vs. -6.78%, p = 0.009, -1.59 vs. -3.98, p = 0.016, respectively). There was no difference in the secondary endpoint of BMD loss on day+365 compared to that on day+100 or baseline at any BMD site. There was no difference in the Z-scores at any site on day+100 or day+365. Conclusions: Prophylactic zoledronate prevented early bone loss on day+100. The indicated preemptive zoledronate beyond day+100 in recipients prevented further bone loss. Patients receiving prophylactic zoledronate may benefit from a supplementary dose of the indicated preemptive zoledronate.

Acute Epigastric Pain: Unexpected Urologic Findings on Computed Tomography.

Mesenteric panniculitis is a relatively common condition encountered on cross-sectional imaging and is mostly asymptomatic. We present one such case where an underlying malignancy was brought to forefront due to associated mesenteric panniculitis presenting as acute abdomen.

Low-grade myofibroblastic sarcoma of the mandible: A rare tumour of childhood.

Low-grade myofibroblastic sarcoma is a rare and indolent tumour of soft tissue. This tumour is relatively common in the head and neck region followed by extremities. Primary low-grade myofibroblastic sarcoma of the mandible is very rarely reported and the occurrence of this tumour in a child is very unusual. A 7-year-old male child presented with a swelling in right angle of mandible. X-ray and computed tomography scan showed a lytic lesion. The lesion was excised and the tissue was sent for histopathological evaluation, which revealed a cellular spindle cell neoplasm arranged in fascicles. The tumour was partly circumscribed and lobulated. On immunohistochemistry (IHC), these tumour cells showed cytoplasmic positivity for vimentin, and smooth muscle actin showed 'tram-track' pattern of positivity. The case was diagnosed as low-grade myofibroblastic sarcoma. There are no definite clinical features or pathognomonic radiological appearances of this tumour that can differentiate this rare tumour from other commonly encountered gnathic bone tumours, such as osteosarcoma, inflammatory myofibroblastic tumour, etc., Histopathological diagnosis coupled with ancillary investigations such as IHC is important to establish a definite diagnosis and rule out the differentials. The exact biological behaviour of this tumour is not known.

Primary Osseous Leiomyosarcoma with Vertebral and Nodal Metastasis in a Young Woman: A Rare Case Report.

Introduction. Primary leiomyosarcoma of bone is rarely described in the literature. In young patients, the clinical and radiological features may mimic relatively common tumours like osteosarcoma. Vertebral and nodal metastasis from osseous leiomyosarcoma is extremely uncommon. Case presentation. A 25-year-old female presented with progressively increasing pain and swelling of the right knee. Clinical and radiological features were suggestive of osteosarcoma. Pre-operative biopsy showed a malignant spindle cell tumour. The surgical resection specimen showed features of leiomyosarcoma of the right proximal tibia. On further evaluation, the patient was found to have an L3-L4 vertebral lesion and histopathological evaluation showed a similar tumour. After 11 months of initial presentation, the patient had axillary lymph node metastasis. Conclusion. Primary osseous leiomyosarcoma should be considered as a differential diagnosis even in young patients presenting with meta-diaphyseal expansile malignant bony lesions. Histology and ancillary studies can confirm the diagnosis.

Comparing the Effectiveness of Propranolol versus Atenolol in Inducing Clinical Clearance in the Treatment of Infantile Haemangioma: A Randomised Controlled Trial.

Background: Despite the excellent clinical efficacy of oral propranolol in the management of infantile haemangiomas (IHs), there is a need to further evaluate other beta blockers that may be equally efficacious but result in lesser adverse effects. We compared the efficacy and short-term safety of atenolol, a hydrophilic cardio-selective beta blocker, with propranolol, in the treatment of IHs. Materials and Methods: Sixty patients with complicated and/or cosmetically significant IHs were randomised into two groups, oral propranolol group (2 mg/kg/day) and the oral atenolol (1 mg/kg/day) group, respectively, for 9 months. Patients were assessed clinically, by the use of Doppler ultrasonography (USG) and measurement of serum hypoxia-inducible factor 1 alpha (HIF-1α). Results: Twenty-two of 30 patients achieved complete clearance in the propranolol group (0.73; 95% CI = 0.54 to 0.87) compared with 13 of 25 patients in the atenolol group (0.52; 95% CI = 0.31 to 0.72). The mean time to achieve Physician Global Assessment Score 5 (PGA5) (25.00 ± 8.87 weeks) was significantly lesser in the propranolol group versus the atenolol group (31.69 ± 7.01 weeks; log-rank = 0.04). The two groups were comparable in terms of adverse effect profile, degree of volume reduction in USG and reduction in HIF-1α levels. Conclusions: Propranolol (2 mg/kg/day) is better than atenolol (1 mg/kg/day) in inducing complete clinical clearance of IH although the results need to be reproduced in larger studies.

Ultrasound and magnetic resonance imaging of hands in systemic sclerosis: A cross-sectional analytical study of prevalence of inflammatory changes in patients with subclinical arthropathy.

Objectives: Prevalence of synovitis, tenosynovitis, erosions, acro-osteolysis and bone marrow edema in systemic sclerosis is not extensively reported. We aimed to estimate the prevalence of changes in individual joints of hands in systemic sclerosis patients. Method: A cross-sectional analytical study consisting of 34 adults (females, n = 32) with systemic sclerosis. Patients with clinical synovitis were excluded. All patients underwent ultrasound (US) and magnetic resonance imaging of bilateral hands. Results: On US, synovitis, tenosynovitis, erosions, and acro-osteolysis were detected in 97%, 94%, 97%, and 29% patients. Grade I synovitis observed in 67% joints-first carpometacarpal joint (55%), first metacarpophalangeal joint (54%), distal radioulnar joint (50%), and intercarpal joints (47%) were commonly affected. Erosions were common in distal phalanges (first DP72% to fifth DP39%). On magnetic resonance imaging, synovitis, tenosynovitis, erosions, and bone edema were observed in 91%, 85%, 97%, and 85% patients. Grade I synovitis was seen in 70% joints, affecting intercarpal joint (70.6%) and third metacarpophalangeal joint (52.9%) commonly. Grade I erosions were seen in 61%, affecting distal phalanges (55.8%), capitate (60.3%), and lunate (55.8%). Grade I edema was commonly affecting lunate (39%) and capitate (26%). On magnetic resonance imaging, acro-osteolysis was present in 28% (97/340) distal phalanges. Fair agreement (0.21-0.40) was noted between US and magnetic resonance imaging for synovitis and erosions. Conclusion: High prevalence of low-grade inflammation is found in systemic sclerosis patients on US and magnetic resonance imaging. Distal joint assessment in addition to proximal joints improves accurate estimation of prevalence of early arthropathy.

Role of shear wave elastography in treatment follow-up of leprosy neuropathy.

PURPOSE: Grayscale ultrasonography when complemented with shear wave elastography helps in better evaluation of treatment response of leprosy neuropathy and in guiding appropriate management of the patient. There is limited literature regarding the use of shear wave elastography in ulnar nerve neuropathy. Our purpose was to evaluate the role of shear wave elastography in assessing stiffness changes within the ulnar nerve during treatment of leprosy. METHODS: This was a prospective study which included 30 patients diagnosed with leprosy neuropathy. Recruited patients were followed up, during the course of treatment, i.e. for 1 year. Serial ultrasonography of these patients was done at 0, 3, 6 and 12 months interval. RESULTS: Significant (P < 0.05) decrease in elastography parameters was seen in transverse imaging plane between first and third, as well as first and fourth visits (mean stiffness and velocity pretreatment ~ 25.78 ± 18 kPa and 2.74 ± 0.98 m/s, mean stiffness and velocity post-treatment 15.67 ± 5.89 kPa and 2.24 ± 0.428 m/s). Although elastography parameters decreased during these visits in the long-axis imaging plane, they were not found to be statistically significant. However, gross morphology and cross-sectional area of the nerve did not change significantly across visits. Interestingly, elastography values were higher in patients with neuritis, though not statistically significant. CONCLUSION: Shear wave elastography is a novel, upcoming modality in musculoskeletal imaging especially in the evaluation of peripheral neuropathy. It can act as an adjunct to grey-scale imaging, which can help in early diagnosis and in guiding treatment of leprosy neuropathy.