Unilateral retinoblastoma; natural history and an age-based protocol in 248 patients

ObjectivesWe aimed to study the clinical state and prognosis of patients with unilateral retinoblastoma who were being treated at a paediatric comprehensive cancer centre in a limited-resource country, to assess the different phases of treatment and the success of different, more complex real-life models.SubjectsIn this retrospective study, we created a snapshot of our retinoblastoma database for the period between 2007 and 2015. Patients whose data were included in the study were followed up until 2016. Out of a total of 744 screened patients, we included data of 248 patients who had been diagnosed with unilateral retinoblastoma.ResultsAs classified as per the International Retinoblastoma Classification, 1 patient presented with group A, 21 with group B, 39 with group C, 104 with group D and 83 with group E retinoblastoma. Chemotherapy was the initial line of treatment in 115 patients and enucleation in 133 others. Later, 141 patients (56.9%) required further management. Patients had a mean ocular survival time of 20.8 months. Nine patients developed extraocular disease at a later stage of management: five after upfront enucleation and four after neoadjuvant chemotherapy. Mean overall survival time stood at 90.2 months. Four and three deaths were recorded in groups D and E, respectively. A single patient died in the initial chemotherapy arm, while six passed away in the initial enucleation arm.ConclusionOur study highlights the importance of initial chemotherapy and close follow-up after enucleation of classes D and E affected eyes even in absence of germline mutations.Subject terms: Paediatrics, Retinal diseases     

Giant calcified cardiomegaly

A 65-year-old male, ex-smoker, with previous extensive anteriormyocardial infarction 18 years ago and NYHA functional     

The Saudi Project for Assessment of Coronary Events (SPACE) registry: Design and results of a phase I pilot study

OBJECTIVE:

The delay between the availability of clinical evidence and its application to the care of patients with acute coronary syndrome (ACS) in the Kingdom of Saudi Arabia remains undefined. The Saudi Project for Assessment of Coronary Events (SPACE) registry provides a comprehensive view of the current diagnostic and treatment strategies for patients with ACS; thus, the registry may be used to identify opportunities to improve the care of these patients.

METHODS:

Eight hospitals in different regions of Saudi Arabia were involved in the pilot phase of the registry, from December 2005 to July 2006. The study patients included individuals with ST segment elevation myocardial infarction (STEMI), non-STEMI and unstable angina.

RESULTS:

A total of 435 patients (77% men and 80% Saudis) with a mean age of 57.1 years were enrolled. Medical history included previously diagnosed ischemic heart disease (32%), percutaneous coronary intervention (12%), diabetes mellitus (53%), hypertension (48%), current smoking (39%), hyperlipidemia (31%) and family history of premature coronary artery disease (11%). The median door-to-needle time for fibrinolytic therapy received by patients with STEMIs was 90 min. Inhospital medications included acetylsalicylic acid (98%), clopidogrel (73%), angiotensin-converting enzyme inhibitors (74%), beta-blockers (73%), statins (88%), unfractionated heparin (80%), low-molecular weight heparin (22%) and glycoprotein IIb/IIIa inhibitors (9%). The inhospital mortality rate was 5%.

CONCLUSION:

The first nationwide registry of patients with ACS in the Kingdom of Saudi Arabia is presented. In contrast to registries from developed countries, our cohort is characterized by a younger age at presentation and a much higher prevalence of diabetes mellitus. Most patients with STEMIs did not receive fibrinolytic therapy within the time recommended in the American College of Cardiology/American Heart Association guidelines. The results of the present pilot study show potential targets for improvement in care.     

The management of familial hypercholesterolaemia in Morocco

Familial hypercholesterolaemia (FH) is an autosomal dominant disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C) as a result of mutations that impair their removal from plasma.The clinical consequence is a high risk of premature cardiovascular disease. Because of the extreme risk of mortality and morbidity, diagnosis, recruitment and management of FH patients must be one of the priorities of public health. In Morocco, specialized consultation for dyslipidaemia and strategy for management of this cardiovascular major risk factor does not exist, making FH identification and management difficult. In this review, we present the first FH state of the art in our country through a sample of 66 subjects. By this analysis, we have tried to elucidate some points that impede the identification and recruitment of heterozygous FH and the management of both heterozygous and homozygous FH in Morocco. Also, we have attempted to propose some strategies for an adequate management of FH in our country, taking into account the local specifications.     

The heat shock protein 90 inhibitor 17-AAG induces cell cycle arrest and apoptosis in mantle cell lymphoma cell lines by depleting cyclin D1, Akt, Bid and activating caspase 9

Mantle cell lymphoma (MCL), a distinct type of non-Hodgkin lymphoma, is characterised by the overexpression of cyclin D1. Heat shock protein 90 (HSP90) is a molecular chaperon to proteins that regulate cell cycle and survival. 17-allylamino-17-demethoxy-geldanamycin (17-AAG), a HSP90 small molecule inhibitor, induced G(0/1) cell cycle arrest and cell death in a dose- and time-dependent manner in MCL cell lines. This effect was associated with the downregulation of cyclin D1, cdk4 and Akt, depletion of Bid, and activation of the intrinsic/mitochondrial caspase pathway. These data suggest that 17-AAG may have a potential therapeutic value in patients with MCL.     

Risk of medication safety incidents with antibiotic use measured by defined daily doses

Background Medication incidents (MIs) account for 11.3 % of all reported patient-safety incidents in England and Wales. Approximately one-third of inpatients are prescribed an antibiotic at some point during their hospital stay. The WHO has identified incident reporting as one solution to reduce the recurrence of adverse incidents. Objectives The aim of this study was to determine the number and nature of reported antibiotic-associated MIs occurring in inpatients and to use defined daily doses (DDDs) to calculate the incident rate for the antibiotics most commonly associated with MIs at each hospital. Setting Two UK acute NHS teaching hospitals. Methods Retrospective quantitative analysis was performed on antibiotic-associated MIs reported to the risk management system over a 2-year period. Quality-assurance measures were undertaken before analysis. The study was approved by the clinical audit departments at both hospitals. Drug consumption data from each hospital were used to calculate the DDD for each antibiotic. Main outcome measures The number of antibiotic-related MIs reported and the incident rate for the 10 antibiotics most commonly associated with MIs at each hospital. Results Healthcare staff submitted 6,756 reports, of which 885 (13.1 %) included antibiotics. This resulted in a total of 959 MIs. Most MIs occurred during prescribing (42.4 %, n = 407) and administration (40.0 %, n = 384) stages. Most common types of MIs were omission/delay (26.3 %, n = 252), and dose/frequency (17.9 %, n = 172). Penicillins (34.5 %, n = 331) and aminoglycosides (16.6 %, n = 159) were the most frequently reported groups with co-amoxiclav (16.8 %, n = 161) and gentamicin (14.1 %, n = 135) the most frequently reported drugs. Using DDDs to assess the incident rate showed that cefotaxime (105.4/10,000 DDDs), gentamicin (25.7/10,000 DDDs) and vancomycin (23.7/10,000 DDDs) had the highest rates. Conclusions This study highlights that detailed analysis of data from reports is essential in understanding MIs and developing strategies to prevent their recurrence. Using DDDs in the analysis of MIs allowed determination of an incident rate providing more useful information than the absolute numbers alone. It also highlighted the disproportionate risk associated with less commonly prescribed antibiotics not identified using MI reporting rates alone.     

Direct mean strain estimation for elastography using nearest-neighbor weighted least-squares approach in the frequency domain

Ultrasound elastography is emerging with enormous potential as a medical imaging modality for effective discrimination of pathological changes in soft tissue. It maps the tissue elasticity or strain due to a mechanical deformation applied to it. The strain image most often calculated from the derivative of the local displacement field is highly noisy because of the de-correlation effect mainly due to unstable free-hand scanning and/or irregular tissue motion; consequently, improving the SNR of the strain image is still a challenging problem in this area. In this paper, a novel approach using the nearest-neighbor weighted least-squares is presented for direct estimation of the ‘mean’ axial strain for high quality strain imaging. Like other time/frequency domain reported schemes, the proposed method exploits the fact that the post-compression rf echo signal is a time-scaled and shifted replica of the pre-compression rf echo signal. However, the elegance of our technique is that it directly computes the mean strain without explicitly using any post filter and/or previous local displacement/strain estimates as is usually done in the conventional approaches. It is implemented in the short-time Fourier transform domain through a nearest-neighbor weighted least-squares-based Fourier spectrum equalization technique. As the local tissue strain is expected to maintain continuity with its neighbors, we show here that the mean strain at the interrogative window can be directly computed from the common stretching factor that minimizes a cost function derived from the exponentially weighted windowed pre- and post-compression rf echo segments in both the lateral and axial directions. The performance of our algorithm is verified for up to 8% applied strain using simulation and experimental phantom data and the results reveal that the SNR of the strain image can be significantly improved compared to other reported algorithms in the literature. The efficacy of the algorithm is also tested with in vivo breast data known to have malignant or benign masses from histology.     

Molecular characterization of Joubert syndrome in Saudi Arabia

Joubert syndrome (JS) is a ciliopathy that is defined primarily by typical cerebellar structural and ocular motility defects. The genetic heterogeneity of this condition is significant with 16 genes identified to date. We have used a combination of autozygome‐guided candidate gene mutation analysis and exome sequencing to identify the causative mutation in a series of 12 families. The autozygome approach identified mutations in RPGRIP1L, AHI1, TMEM237, and CEP290, while exome sequencing revealed families with truncating mutations in TCTN1 and C5ORF42. Our study, the largest comprehensive molecular series on JS, provides independent confirmation of the recently reported TCTN1, TMEM237, and C5ORF42 as bona fide JS disease genes, and expands the allelic heterogeneity of this disease. Hum Mutat 33:1423–1428, 2012. © 2012 Wiley Periodicals, Inc.