Assessment by miRNA microarray of an autologous cancer antigen-pulsed adoptive immune ensemble cell therapy (AC-ACT) approach; demonstrated induction of anti-oncogenic and anti-PD-L1 miRNAs.

A 60-year-old woman with stage IV rectal cancer received adoptive cell therapy with autologous cancer antigen (AC-ACT) causing induction of anti-oncogenic and anti-PD-L1 miRNAs as assessed by miRNA microarray. More than 1 year after AC-ACT, metastases have been arrested, and the patient reports good quality of life.

[Microbiological profile of endophthalmitis in a referral centre in Tunisia]. / Profil microbiologique des endophtalmies aiguës dans un centre de référence en Tunisie.

PURPOSE: To investigate the microbiological profile of acute postoperative endophthalmitis in a referral center in Tunisia and to assess the antibiotic sensitivity of the organisms. PATIENTS AND METHODS: This is a retrospective study over a period of eleven years, conducted on patients hospitalized with acute infectious postoperative endophthalmitis. Cultures were performed on aqueous (93%) and vitreous specimens (68%) obtained at presentation. Each sample underwent direct examination, culture and antibiotic susceptibilities. RESULTS: The number of acute postoperative endophthalmitis cases identified during the study period was 308. Organisms were found in 43% of samples (endophthalmitis was bacterial in 39.5%, fungal in 0.9% and polymicrobial in 2.6%). Cultures grew primarily Staphylococcus epidermidis in 31.4% of cases, Streptococcus pneumoniae in 22.7% of cases and Staphylococcus aureus in 12.7% of cases. Gram-positive cocci are more sensitive to vancomycin and Gram-negative bacilli are more susceptible to ofloxacin and ciprofloxacin. CONCLUSION: In our study, microbiological samples were positive in 43% and coagulase-negative Gram-positive cocci are the most common organisms. However, antibiotic resistance has been increasing over the years.

[Foveal choroidal thickness assessment with SD-OCT in high myopic glaucoma]. / Épaisseur choroïdienne fovéolaire en OCT-SD dans le glaucome du myope fort.

PURPOSE: To measure macular choroidal thickness (CT) using spectral domain optical coherence tomography (OCT) in high myopic eyes with primary angle-open glaucoma (POAG), and to investigate whether the choroid is thinner in these eyes compared to high myopic eyes without glaucoma. PATIENTS AND METHODS: We conducted a cross-sectional study of forty-eight eyes with high myopic glaucoma matched with 48 highly myopic eyes without glaucoma by age, central corneal thickness and axial length (AL). OCT scans were performed with the spectral domain OCT (Topcon 2000). The subfoveal CT was measured between the Bruch membrane and the internal aspect of the sclera. RESULTS: In the subgroup without glaucoma, matched with the subgroup with glaucoma (P=0.57), by age, central corneal thickness (P=0.33) and AL (P=0.10), the mean subfoveal CT was 96.32 µm ± 39.56 µm. In the subgroup with glaucoma, the mean subfoveal CT was 50.44 µm ± 16.36 µm. The comparison between the two subgroups found a statistically significant difference in subfoveal CT (P<10(-4)). CONCLUSIONS: Foveal choroidal thickness is reduced in highly myopic eyes with glaucoma. The choroidal thinning can be a useful parameter for the diagnosis and the follow-up of highly myopic patients with glaucoma.

[Factors linked to foveoschisis in high myopia]. / Étude des facteurs associés au fovéoschisis dans la myopie forte.

PURPOSE: To investigate the factors linked to foveoschisis in high myopia. METHODS: Retrospective study of 113 patients (200 eyes) with high myopia was conducted between January 2010 and June 2012. Subjects underwent a complete ophthalmic examination, spectral domain optical coherence tomography (OCT TOPCON 2000) and ocular echography. RESULTS: Of the 200 eyes, 22 (11%) had foveoschisis on OCT examination. On the basis of univariate analysis, five variables were associated with the pathologic changes, including spherical equivalent over 10 diopters (P=0.044), axial length over 30 mm (P=0.0028), macular chorioretinal atrophy (P=0.0009), posterior staphyloma (P=0.0007) and vitreoretinal interface factors (P=0.0002). In the multivariate analysis, three factors were independently associated with foveoschisis in high myopia: axial length (adjusted OR, 16.7; IC 95% 1.4-219.7, P=0.036), macular chorioretinal atrophy (adjusted OR, 13.2; IC 95%, 1.3-133.1, P=0.044), and vitreoretinal interface factors (adjusted OR, 36.1; IC 95%, 3.5-376.9, P=0.002). CONCLUSIONS: In our study, axial length, macular chorioretinal atrophy, and vitreoretinal interface factors were independently associated foveoschisis in highly myopic eyes.

[Choroidal thickness assessment with SD-OCT in high myopia with dome-shaped macula]. / Épaisseur choroïdienne fovéolaire au SD-OCT dans la myopie forte avec macula bombée.

PURPOSE: To measure macular choroidal thickness (CT) using spectral-domain optical coherence tomography (SD-OCT) in highly myopic eyes with dome-shaped macula (DSM), and to investigate whether the choroid is thicker in these eyes compared to highly myopic eyes without MB. PATIENTS AND METHODS: A cross-sectional study of 200 eyes was performed between January 2010 and June 2012. Twenty-four highly myopic eyes (12%) had a dome-shaped macula. All patients underwent a complete ophthalmological examination, SD-OCT (TOPCON 2000), and B-scan ultrasonography. OCT scans were analyzed in 7 sections, and subfoveal CT was measured manually between the Bruch's membrane and the internal aspect of the sclera. The 20 eyes with isolated dome-shaped macular were paired by age and axial length (AL) with 20 eyes without macular involvement. RESULTS: In the subgroup with isolated MB, the mean subfoveal CT was 101.86 µm (± 21.35 µm). A statistically significant negative correlation was found between CT and AL (r=-0.623, P=0.0001). The regression equation demonstrated a decrease of 8.3 µm per mm of AL. In the subgroup without MB, matched with the subgroup with MB by age (P=0.591), and AL (P=0.815), the mean subfoveal CT was 89.54 µm (± 20.12 µm). The comparison between the two subgroups found a statistically significant difference in subfoveal CT (P<10-4). CONCLUSIONS: In our study, choroidal thickness is increased in highly myopic eyes with dome-shaped macula compared to highly myopic eyes without dome-shaped macula. These findings suggest that abnormalities of the choroid may play a role in the pathogenesis of dome-shaped macula.

HIV-Care Outcome in Saudi Arabia; a Longitudinal Cohort.

BACKGROUND: Clinical characteristics of HIV-1 infection in people inhabiting Western, Sub-Saharan African, and South-East Asian countries are well recognized. However, very little information is available with regard to HIV-1 infection and treatment outcome in MENA countries including the Gulf Cooperation Council (GCC) states. METHODS: Clinical, demographic and epidemiologic characteristics of 602 HIV-1 infected patients followed in the adult Infectious Diseases Clinic of King Faisal Specialist Hospital and Research Centre, in Riyadh, Kingdom of Saudi Arabia a tertiary referral center were longitudinally collected from 1989 to 2010. RESULTS: Of the 602 HIV-1 infected patients in this observation period, 70% were male. The major mode of HIV-1 transmission was heterosexual contact (55%). At diagnosis, opportunistic infections were found in 49% of patients, most commonly being pneumocysitis. AIDS associated neoplasia was also noted in 6% of patients. A hundred and forty-seven patients (24%) died from the cohort by the end of the observation period. The mortality rate peaked in 1992 at 90 deaths per 1000 person-year, whereas the mortality rate gradually decreased to <1% from 1993-2010. In 2010, 71% of the patients were receiving highly active retroviral therapy. CONCLUSIONS: These data describe the clinical characteristic of HIV-1-infected patients at a major tertiary referral hospital in KSA over a 20-year period. Initiation of antiretroviral therapy resulted in a significant reduction in both morbidity and mortality. Future studies are needed in the design and implementation of targeted treatment and prevention strategies for HIV-1 infection in KSA.

[Epidemiology of uveitis in the Tunis area]. / Profil épidémiologique des uvéites dans la région de Tunis.

PURPOSE: To identify the epidemiological characteristics and the most common etiologies of uveitis in the Tunis area. METHODS: Medical records for all uveitis patients seen from September 2003 through October 2009 were included. RESULTS: A total of 424 patients (596 eyes) were included. The mean age at onset of uveitis was 36 years, and the male-to-female ratio was 0.66. Uveitis was unilateral in 56.4%. Anterior uveitis was most common (48%), followed by panuveitis (33.6%), posterior uveitis (13.3%), and intermediate uveitis (5%). The most common causes were Behçet disease (14.7%), toxoplasmosis (10.2%), Vogt-Koyanagi-Harada (VKH) syndrome (3.7%) and sarcoidosis (3.3%). Retinal vasculitis was found in 20%. Behçet disease was the most common cause of chronic uveitis. The most common complications were cataract (21.6%), ocular hypertension (12%) and macular edema (5.6%). CONCLUSION: In our study, the most common causes of uveitis were Behçet disease, toxoplasmosis, VKH syndrome and sarcoidosis.

Profiling of normal and malignant breast tissue show CD44high/CD24low phenotype as a predominant stem/progenitor marker when used in combination with Ep-CAM/CD49f markers.

BACKGROUND: Accumulating evidence supports cancer to initiate and develop from a small population of stem-like cells termed as cancer stem cells (CSC). The exact phenotype of CSC and their counterparts in normal mammary gland is not well characterized. In this study our aim was to evaluate the phenotype and function of stem/progenitor cells in normal mammary epithelial cell populations and their malignant counterparts. METHODS: Freshly isolated cells from both normal and malignant human breasts were sorted using 13 widely used stem/progenitor cell markers individually or in combination by multi-parametric (up to 9 colors) cell sorting. The sorted populations were functionally evaluated by their ability to form colonies and mammospheres, in vitro. RESULTS: We have compared, for the first time, the stem/progenitor markers of normal and malignant breasts side-by-side. Amongst all markers tested, we found CD44high/CD24low cell surface marker combination to be the most efficient at selecting normal epithelial progenitors. Further fractionation of CD44high/CD24low positive cells showed that this phenotype selects for luminal progenitors within Ep-CAMhigh/CD49f + cells, and enriches for basal progenitors within Ep-CAM-/low/CD49f + cells. On the other hand, primary breast cancer samples, which were mainly luminal Ep-CAMhigh, had CD44high/CD24low cells among both CD49fneg and CD49f + cancer cell fractions. However, functionally, CSC were predominantly CD49f + proposing the use of CD44high/CD24low in combination with Ep-CAM/CD49f cell surface markers to further enrich for CSC. CONCLUSION: Our study clearly demonstrates that both normal and malignant breast cells with the CD44high/CD24low phenotype have the highest stem/progenitor cell ability when used in combination with Ep-CAM/CD49f reference markers. We believe that this extensive characterization study will help in understanding breast cancer carcinogenesis, heterogeneity and drug resistance.

[Management of rhegmatogenous retinal detachment with unseen breaks: about 50 cases]. / Prise en charge des decollements de retine rhegmatogenes sans dechirure visible: a propos de 50 cas.

PURPOSE: To evaluate the clinical and therapeutic characteristics of rhegmatogenous retinal detachment (RRD) with unseen retinal breaks. PATIENTS AND METHODS: Retrospective study 50 eyes (50 patients) with RRD with unseen retinal breaks in the pre and intraoperative examination. These patients were treated between 2005 and 2010 by vitrectomy or scleral buckling. Retinal breaks were meticulously sought by indentation of the vitreous base. The subretinal fluid was drained by a peripheral retinotomy when a vitrectomy was needed and puncture ab externo when a scleral buckling was performed. RESULTS: A retinal detachment with unseen retinal breaks accounted for 15% of all RRD operated during this 5-year duration period (2005 - 2010). The average age of our patients was 57 years.Ten were myopic (20%) and 27 (54%) pseudophakic, with inferior RRD in 60% of the cases cases while advanced vitreoretinal proliferation (PVR) greater or equal to stage C in was present in 72%. Primary vitrectomy was performed in 46 cases. Retinal reattachment rate was achieved after a single procedure in 41 eyes (82%). Among them, 40 were operated by vitrectomy and one eye by scleral buckling. The recurrence rate was significantly higher in patients operated by scleral buckling (75%) than by vitrectomy (15%). CONCLUSION: RRD with unseen retinal breaks are often seen inferiorly and have a chronic evolution (60%). They concern pseudophakic patients in the majority of the cases. Their poor prognosis and high recurrence rate also appear to be related to an advanced PVR (72%). The good results of primary vitrectomy should be confirmed by randomized studies, especially in phakic eyes.

[Clinical characteristics and therapeutic challenges of retinal detachment in highly myopic eyes]. / Particularités cliniques et thérapeutiques du décollement de rétine du myope fort: à propos de 83 cas.

PURPOSE: To evaluate the clinical characteristics and therapeutic challenges of retinal detachment in highly myopic eyes. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 83 eyes in 79 patients with high myopia (> 6.00 diopters or axial length > or = 26.00 mm) who underwent surgery for retinal detachment between 2001 and 2008. The surgical approaches depended on the type and location of the retinal break, the degree of myopia, and the grade of PVR. RESULTS: The mean age of patients (48 men and 31 women) was 53.9 years. Refractive error ranged from - 10 D to - 25 D (mean was - 14.0 D). The mean follow-up was 19.4 months. Peripheral or equatorial retinal tears were present in 52 cases (62.6%), a macular hole in 14 cases (16.8%), a giant retinal tear in 6 cases (7.2%), and posterior paravascular retinal tears in 11 cases (13.2%). Single-surgery anatomic success was achieved in 65 cases (78.3%), with 17 cases after scleral buckle surgery and 46 cases after pars plana vitrectomy. Final anatomic success was achieved in 76 cases (91.5%). Per and postoperative hemorrhagic complications occurred in 16 cases (19.2%). CONCLUSION: Retinal detachment is a serious complication of high myopia. It often occurs in young patients. Treatment is difficult due to anatomical and clinical conditions.

Genetic diagnosis in consanguineous families with kidney disease by homozygosity mapping coupled with whole-exome sequencing.

BACKGROUND: Accurate diagnosis of the primary cause of an individual's kidney disease can be essential for proper management. Some kidney diseases have overlapping histopathologic features despite being caused by defects in different genes. In this report, we describe 2 consanguineous Saudi Arabian families in which individuals presented with kidney failure and mixed clinical and histologic features initially believed to be consistent with focal segmental glomerulosclerosis. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We studied members of 2 apparently unrelated families from Saudi Arabia with kidney disease. MEASUREMENTS: Whole-genome single-nucleotide polymorphism analysis followed by targeted isolation and sequencing of exons using genomic DNA samples from affected members of these families, followed by additional focused genotyping and sequence analysis. RESULTS: The 2 apparently unrelated families shared a region of homozygosity on chromosome 2q13. Exome sequence from affected individuals lacked sequence reads from the NPHP1 gene, which is located within this homozygous region. Additional polymerase chain reaction-based genotyping confirmed that affected individuals had NPHP1 deletions, rather than defects in a known focal segmental glomerulosclerosis-associated gene. LIMITATIONS: The methods used here may not result in a clear genetic diagnosis in many cases of apparent familial kidney disease. CONCLUSIONS: This analysis shows the power of new high-throughput genotyping and sequencing technologies to aid in the rapid genetic diagnosis of individuals with an inherited form of kidney disease. We believe it is likely that such tools may become useful clinical genetic tools and alter the manner in which diagnoses are made in nephrology.

[Ophthalmologic manifestations of congenital rubella]. / Manifestations ophtalmologiques de la rubéole congénitale.

Congenital rubella is a rare and serious disease including auditory neurological, cardiac, urinary, and ocular abnormalities. The eye complaints are often congenital cataract, congenital glaucoma, microphthalmia, and oculomotor disorders. We report the case of a 6-year-old girl presenting with a unilateral congenital cataract associated with congenital rubella. She was referred for complaints of high myopia in her right eye. She had a family history of cardiac and urogenital malformations, and presented deafness at birth. The ophthalmologic examination showed a microcornea and a unilateral dense congenital cataract in the right eye. B-scan ophthalmic ultrasound revealed a posterior microphthalmos. The anterior segment examination of the left eye was normal. Funduscopy revealed a salt-and-pepper appearance. Laboratory tests revealed a positive serology, confirming the congenital rubella. Given her complaints of loss of visual acuity in the right eye, the patient was operated on with a phacoaspiration implant in the capsular bag. The postoperative course was uneventful. The prevention of congenital rubella is based on routine vaccination of children. The association of cataract, congenital heart defects, and deafness must be systematically investigated as it may be more serious in association with systemic manifestations.

Characterization of the expression of HTm4 (MS4A3), a cell cycle regulator, in human peripheral blood cells and normal and malignant tissues.

HTm4 (MS4A3) is a member of a family of four-transmembrane proteins designated MS4A. MS4A proteins fulfil diverse functions, acting as cell surface signalling molecules and intracellular adapter proteins. Early reports demonstrated that HTm4 is largely restricted to the haematopoietic lineage, and is involved in cell cycle control, via a regulatory interaction with the kinase-associated phosphatase, cyclin A and cyclin-dependent kinase 2 (CDK2). Here we describe the expression pattern of HTm4 in peripheral blood cells using gene expression microarray technology, and in normal foetal and adult human tissues, as well as adult human cancers, using tissue microarray technology. Using oligonucleotide microarrays to evaluate HTm4 mRNA, all peripheral blood cell types demonstrated very low levels of HTm4 expression; however, HTm4 expression was greatest in basophils compared to eosinophils, which showed lower levels of HTm4 expression. Very weak HTm4 expression is found in monocytes, granulocytes and B cells, but not in T cells, by lineage specific haematopoietic cell flow cytometry analysis. Interestingly, phytohaemagglutinin stimulation increases HTm4 protein expression in peripheral blood CD4-T-lymphocytes over nearly undetectable baseline levels. Western blotting and immunohistochemical studies show strong HTm4 expression in the developing haematopoietic cells of human foetal liver. Immunohistochemical studies on normal tissue microarrays confirmed HTm4 expression in a subset of leucocytes in nodal, splenic tissues and thymic tissue, and weak staining in small numbers of cell types in non-haematopoietic tissues. Human foetal brain specimens from 19 to 31 gestational weeks showed that the strongest-staining cells are ventricular zone cells and the earliest-born, earliest-differentiating 'pioneer' neurons in the cortical plate, Cajal-Retzius and, to a lesser extent, subplate-like neurons. Malignant tissue microarray analysis showed HTm4 expression in a wide variety of adenocarcinomas, including breast, prostate and ovarian. These findings warrant the further study of the role of HTm4 in the cell cycle of both haematopoietic and tumour cells.

Transplant tourism outcome: a single center experience.

BACKGROUND: Transplant tourism is the term used for patients who travel abroad for transplantation. Transplant tourism has always been surrounded with controversy regarding how these organs were obtained, the donor's care after transplantation, and the recipient outcome. Many authors have found that the outcome of the recipients in transplant tourism is inferior to those transplanted in their own countries. However, most these studies were small, with the latest one including only 33 patients. Here, we describe the outcome of 93 patients who were transplanted abroad compared with local transplantation. MATERIAL AND METHODS: All transplant patients who were followed up at our Nephrology Clinic from 1998 until 2008 were identified using our data base system. We selected patients transplanted from 2003 and forward because the computerized system for laboratory and electronic records began operation that year. RESULTS: A total of 165 patients were identified (93 in the tourist group and 72 in the local one). Transplant tourists had a higher rate of acute rejection in the first year compared with local transplantation (27.9% vs. 9.9, P=0.005), higher mean creatinine at 6 months and 1 year (120 vs. 101 micromol/L, P=0.0007, 113 vs. 98 micromol/L, P=0.008). There was no statistical difference in graft or patient survival in 1 or 2 years after transplantation. However, transplant tourist had a higher rate of cytomegalovirus infection (15.1% vs. 5.6%, P=0.05) and hepatitis C seroconversion (7.5% vs. 0%, P=0.02). CONCLUSION: Transplant tourists had a more complex posttransplantation course with higher incidence of acute rejection and infectious complications.