MYD88 L265P mutation in intraocular lymphoma: A potential diagnostic marker

Purpose:Vitreoretinal lymphoma (VRL) is the most common intraocular lymphoma (IOL). This can be either primary or secondary to the central nervous system lymphoma. The diagnosis of primary intraocular lymphoma (PIOL) currently relies on clinical diagnosis and cytological analysis of the vitreous or subretinal biopsy. Although most cases are diagnosed without much issue, the limited amount of vitreous fluid, subjectivity in cytological reporting, and special expertise in ocular pathology make the diagnosis challenging. MYD88 L265P mutation has been implicated to have diagnostic utility in PIOL. In this study, we screened consecutive vitreous biopsies for the presence of MYD88 L265P mutation to understand its diagnostic utility compared to conventional cytological analysis.Methods:Cytological analysis and MYD88 L265P mutation by PCR-based sequencing and restriction fragment length polymorphism (RFLP) were carried out on consecutive vitreous and subretinal biopsies collected from 21 patients. The diagnostic utility of the cytology and MYD88 L265P mutation analysis were compared.Results:Out of the 21 patients, 15 had clinical suspicion of having PIOL. Out of these suspected cases of PIOL, nine were confirmed on follow-up, while six were diagnosed as other intraocular pathologies. Diagnostic utility of MYD88 L265P mutation analysis revealed a sensitivity of 88.9%, specificity of 91.6%, positive and negative predictive value of 88.9% and 91.7%, respectively. Diagnostic accuracy of 90.5% was achieved with the mutation analysis that shows the superiority of MYD88 in both ruling in and ruling out PIOL. The diagnostic utility of MYD88 L265P mutation was superior to conventional cytological analysis.Conclusion:The analysis of MYD88 L265P mutation is reliable and efficient in the diagnosis of PIOL.     

Echocardiography in the diagnosis of apical non-compaction associated with congenital heart diseases

Background

Isolated left ventricular non-compaction has been reported extensively. However, apical non-compaction of both ventricles and the interventricular septum (IVS) is not often reported in the literature. The objective of our study is to evolve the echocardiographic diagnostic criteria and to assess the types and impact of the associated lesions in “apical non-compaction”.

Methods and results

Seventy consecutive cases that fulfilled standard echocardiographic criteria for non-compaction of the left ventricle and, in addition, N/C ratio of >3 for the right ventricle and apical IVS formed the material. The age of patients ranged from 3 days to 35 years, with 37 males and 33 females. The associated lesions were present in all 70 cases: 62 had acyanotic (88.6 %) and 8 had cyanotic congenital heart diseases (11.4 %). Of the 70 cases, 18 had pump failure (25.7 %): 8 cases had left ventricular dysfunction, 7 had right ventricular dysfunction, and 3 had biventricular dysfunction; 33 (47.1 %) had pulmonary hypertension, 2 (2.9 %) had thrombus, and 1 (1.4 %) had tachyarrhythmia. Pump failure was worsened by volume overload in 33.9 % and by pressure overload in 8.1 % of cases. Some very rare lesions were detected. All 70 cases had Swiss cheese appearance of the apical half of the IVS, looking like the delta of a river.

Conclusion

All of the apical non-compaction syndrome cases had associated lesions, mostly acyanotic congenital heart disease with volume overload, rather than obstructive lesions. Transthoracic echocardiography plays an important role in the diagnosis of apical non-compaction syndrome and associated lesions that worsen the pump failure.     

Atrial synchronous left ventricular only pacing with VDD pacemaker system – A cost effective alternative to conventional cardiac resynchronization therapy

Introduction

Atrial synchronous left ventricular (LV) only pacing using two leads and VDD pacemaker could be a cost effective alternative to conventional cardiac resynchronization therapy (CRT).

Methods

We implanted right atrial (RA) and LV leads with VDD pulse generator (LV only pacing) in five carefully screened heart failure patients who could not afford conventional CRT. All had NYHA class III/IV symptoms despite maximal guideline directed medical therapy. The sensed atrioventricular delay was programmed to pre-excite the LV and achieve fusion beat. Response to treatment was assessed at 6 months.

Results

Four patients were males. The mean age was 58 ± 12 years. At follow up, there was improvement in electrocardiographic, and echocardiographic parameters: Mean QRS duration decreased from 174 ± 17 msec to 128 ± 10.9 msec (p = 0.009), LV end-diastolic diameter decreased from 73.2 ± 12 mm to 65.8 ± 9.6 mm (p = 0.026), LV end-systolic diameter decreased from 65 ± 12 mm to 54 ± 10 mm (p = 0.020). There was a trend towards reduction of LV end-systolic and end-diastolic volumes. LV ejection fraction improved from 25 ± 6% to 34 ± 6% (p = 0.013) and left atrial dimension reduced from 44 ± 4 mm to 39 ± 5 mm (p = 0.045). All patients improved clinically.

Conclusion

RA-LV pacing using VDD pacemaker is a safe and effective technique of CRT. This may be a cost effective alternative to conventional CRT for patients in developing countries.     

OBG‐like ATPase 1 inhibition attenuates angiotensin II‐induced hypertrophic response in human ventricular myocytes via GSK‐3beta/beta‐catenin signalling

Obg‐like ATPase 1 (OLA1) that possesses both GTP and ATP hydrolyzing activities has been shown to be involved in translational regulation of cancer cell growth and survival. Also, GSK3β signalling has been implicated in cardiac development and disease. However, the role of OLA1 in pathological cardiac hypertrophy is unknown. We sought to understand the mechanism by which OLA1 regulates GSK3β‐β‐Catenin signalling and its functional significance in angiotensin‐II (ANG II)‐induced cardiac hypertrophic response. OLA1 function and its endogenous interaction with GSK3β/β‐catenin signalling in cultured human ventricular cardiomyocytes (AC16 cells) and mouse hearts (in vivo) was evaluated with/without ANG II‐stimulated hypertrophic response. ANG II administration in mice increases myocardial OLA1 protein expression with a corresponding increase in GSK3β phosphorylation and decrease in β‐Catenin phosphorylation. Cultured cardiomyocytes treated with ANG II show endogenous interaction between OLA1 and GSK3β, nuclear accumulation of β‐Catenin and significant increase in cell size and expression of hypertrophic marker genes such as atrial natriuretic factor (ANF; NPPA) and β‐myosin heavy chain (MYH7). Intriguingly, OLA1 inhibition attenuates the above hypertrophic response in cardiomyocytes. Taken together, our data suggest that OLA1 plays a detrimental role in hypertrophic response via GSK3β/β‐catenin signalling. Translation strategies to target OLA1 might potentially limit the underlying molecular derangements leading to left ventricular dysfunction in patients with maladaptive cardiac hypertrophy.     

Sorafenib in Dupuytren and Ledderhose Disease

Palmar and plantar fibromatosis are benign proliferative processes which present as a diffuse thickening or nodules of the hands and/or feet and may lead to flexion contractures, pain, and functional impairment known as Dupuytren and Ledderhose diseases, respectively. Current treatments are noncurative and associated with significant morbidity. Here, we report on the outcomes of 5 patients with advanced disease, no longer surgical candidates, treated with sorafenib. Sorafenib exhibited an expected safety profile. All 5 patients demonstrated objective responses as evaluated by a decrease in tumor size and/or tumor cellularity from baseline and all 5 patients reported subjective pain relief and/or functional improvement. Mechanistically, immunohistochemistry revealed patchy positivity for PDGFRβ, a known target of sorafenib. The outcomes of these 5 patients suggest the safety and efficacy of a relatively well-tolerated oral agent in the treatment of Dupuytren and Ledderhose diseases and suggest the need for future controlled studies.     

Synovial chondromatosis of the elbow in a child

Synovial chondromatosis is cartilaginous metaplasia of mesenchymal remnants of synovial tissue of the joints. Its main characteristic is the formation of cartilaginous nodules in the synovium and inside the articular space (loose bodies). It usually presents between the third and fifth decades and is rare in children. It presents as a mono-articular pathology affecting large joints such as the knee, hip, and elbow. The main symptoms are pain, swelling, and limitation of movements in the affected joint. Diagnosis is made by panoramic radiographs, computed tomography scan, and mainly magnetic resonance imaging and on surgery. The authors describe of synovial chondromatosis presenting in the elbow of an 11 year-old girl which is unreported to the best of our knowledge.