Rheumatoid arthritis: A single-center Egyptian experience

Objective: Demonstration of rheumatoid arthritis (RA) characteristics in a large cohort of Egyptian patients.

Methods: Retrospective analysis of data of 3219 RA patients attending the Rheumatology outpatient clinic, Kasr Alainy Hospital, Cairo University; from January 1995 till December 2015.

Results: Mean age at disease onset was 36.1 ±13.4 years; 2774 (84%) were females and mean disease duration was 12.9 ±7.9 years. Regarding number of joint affected at disease onset; polyarticular pattern was found in 77.1%, pattern of joint involvement; combined small and large joints involvement was in 83.2%, subcutaneous nodules in 14.2%, interstitial lung disease in 0.3%, secondary Sjogren’s syndrome in 10.5%, hand bony erosions at diagnosis in 20.6%. Rheumatoid factor was positive in 52%.

There was annual increase in the newly diagnosed cases (P = 0.017) reflecting increase in patients’ awareness and improvement of medical service, also annual increase in: mean age of onset (P < 0.001) reflecting changes in health measures, also in cases with monoarticular or oligoarticular patterns at disease onset (P = 0.02, 0.01 respectively) reflecting earlier diagnosis of patients and in patients with small joint involvement (P = 0.001) with a significant decline in: polyarticular pattern (P = 0.001), combined small and large joint affection (P < 0.001), and number of cases with hand bony erosions (P = 0.01) denoting earlier diagnosis, tight disease control.

Conclusion: We found a female predominance, younger age at disease onset, lower frequency of extra articular manifestations, more frequent polyarticular pattern at disease onset and less erosive disease, denoting changing referral patterns, earlier diagnosis, improved disease control in Egyptian RA patients over 2 decades.

Abbreviations: SNs: Subcutaneous nodules; 2ry SS: 2ry Sjogren’s syndrome; ILD: Interstitial lung disease; ACPA: Anti-cyclic citrullinated peptide antibodies; DMARDs: Disease modifying anti-rheumatic drugs.     

Immune Profiling of T Cells Infiltrating Vitreous Humor in Tubercular Uveitis

Purpose: To assess cellular composition and local cytokine response in vitreous humor of tubercular uveitis.

Methods: Cells were collected from vitreous cassettes and peripheral blood of 8 tubercular uveitis and 5 control subjects, undergoing vitrectomy and analyzed by flow cytometry for cellular composition, activation status, proinflammatory cytokine expression, and uptake of TLR9 ligand, CpG ODN 2216.

Results: CD3 + T cells with equal proportion of CD4+ and CD8 + T cells formed major fraction of infiltrating cells. The vitreous humor showed higher expression of recent activation marker, CD69, and proinflammatory cytokines, IFN-γ and IL-17A, in CD4 + T cells as compared to peripheral blood. Lastly, intraocular CD4 + T cells showed reduced uptake of ODN 2216 than peripheral blood.

Conclusions: Our results indicate that local antigenic stimuli trigger T cell infiltration and activation of CD4 + T cells that are hyporesponsive to TLR9 stimulation. These infiltrating T cells might be responsible in further aggravating ocular inflammation.     

Development and psychometric evaluation of a condom use self-efficacy measure in Spanish and English

Background: Condom self-efficacy is an important construct for HIV/STI prevention and intervention. A psychometrically sound measure of the self-efficacy for using condoms that has been designed for Hispanic women to respond in Spanish or English is needed.

Objectives: The goal of this study was to develop and evaluate a brief self-report measure of condom use self-efficacy.

Methods: We developed a 15-item measure of condom use self-efficacy based on expert knowledge of measurement and HIV/STI prevention with Hispanic women using a translation-back translation approach. Participants were 320 Hispanic women from the Southeastern US.

Results: Internal consistency of the full measure was 92. A short form of the instrument with a subset of five items also had acceptable internal consistency, alpha = .80, and was significantly correlated with the full scale, r_s = .93, p < .001. A single latent factor explained 9–48% of the variation in these items. Evidence of construct validity of the short form was provided by correlations of the scale with two self-report measures of condom use: r_s = .34** with condom use, r_s = .37** with condom use during vaginal sex.

Conclusions: Either the full measure or the five-item measure could be used in studies where condom use is an important behavioral outcome, such as evaluating prevention interventions, with Hispanic women. Future studies should examine the performance of this measure with other groups, including Hispanic men and members of other ethnic and language groups.     

A multi-site community randomized trial of community health workers to provide counseling and support for patients newly entering HIV care in rural Ethiopia: study design and baseline implementation

Background: Although HIV therapy is delivered to millions globally, treatment default (especially soon after entering care) remains a challenge. Community health workers (CHWs) can provide many services for people with HIV, including in rural and resource-limited settings.

Objectives: We designed and implemented a 32 site community randomized trial throughout southern Ethiopia to assess an intervention using CHWs to improve retention in HIV care.

Methods: Sixteen district hospital and 16 local health center HIV clinics were randomized 1:1 to be intervention or control sites. From each site, we enrolled adults newly entering HIV care. Participants at intervention sites were assigned a CHW who provided: HIV and health education; counseling and social support; and facilitated communication with HIV clinics. All participants are followed through three years with annual health surveys, plus HIV clinic record abstraction including clinic visit dates. CHWs record operational data about their client contacts.

Results: 1799 HIV patients meeting inclusion criteria were enrolled and randomized: 59% were female, median age = 32 years, median CD4 + count = 263 cells/mm³, and 41% were WHO Stage III or IV. A major enrollment challenge was fewer new HIV patients initiating care at participating sites due to shortage of HIV test kits. At intervention sites, 71 CHWs were hired, trained and assigned to clients. In meeting with clients, CHWs needed to accommodate to various challenges, including HIV stigma, distance, and clients lacking cell phones.

Conclusions: This randomized community HIV trial using CHWs in a resource-limited setting was successfully launched, but required flexibility to adapt to unforeseen challenges.     

Intra-articular treatment with corticosteroids increases apoptosis in human rotator cuff tears

Purpose: The aim of this study is to evaluate in vivo the level of apoptosis in human rotator cuff tears and the relationship it might have with tendon degeneration.

Methods: Rotator cuff biopsies from 19 male and female patients, ages between 38 and 68 years, with and without previous corticosteroid infiltrations were collected via arthroscopy. Biopsies from seven patients with healthy rotator cuffs were used as a control group. An in situ terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed to detect the level of apoptosis, which was expressed as a percentage of apoptotic cells (PAC).

Results: PAC in patients with corticosteroid infiltrations was 76.97 ± 16.99 in all tendon rupture zones, in non-infiltrated patients was 35.89 ± 22.96, whereas in control patients was 14.48 ± 8.15. Likewise, the tendency of PAC reveals that apoptosis in control and non-infiltrated groups was different and dispersed in all tear zones; while in corticosteroid treated patients, the tendency was similar in all rupture sites.

Conclusions: This investigation leads us to conclude that the administration of corticosteroid is associated with a higher amount of apoptosis at the insertion site of the rotator cuff (rupture edge).     

Long-Term Efficacy,Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study

Background: Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited.

Objective: We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study.

Methods: This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen.

Results: Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA < 50 copies/mL) was 0.79 (95% CI: 0.75, 0.83) at five years. No treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years.

Conclusions: In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function.     

Virologic outcomes in early antiretroviral treatment: HPTN 052

Introduction: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure.

Objective: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052.

Methods: 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350–550 cells/mm³ at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm³ at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation.

Results: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure.

Conclusions: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.     

Identification of specific antibodies against the Ag85C-MPT51-HspX fusion protein (CMX) for serological screening of tuberculosis in endemic area

Objectives: Development of new tools for rapid and accurate diagnosis of tuberculosis (TB) is considered a strategy for controlling the disease. The recombinant CMX fusion protein is composed of immunodominant epitopes of the Ag85C (Rv0129c), MPT51 (Rv3803c) and the entire HspX (Rv2031c) proteins from Mycobacterium tuberculosis H37Rv (Mtb). The aim of this study was to evaluate the applicability of a test using the CMX protein in individuals suspected of TB.

Methods: Indirect ELISA was used to measure serum anti-CMX IgM and IgG in individuals with pulmonary TB.

Results: Patients with pulmonary TB had higher titers of IgM (OD = 0.502 ± 0.281) than healthy controls (OD = 0.200 ± 0.125). The cutoff for IgM-ELISA was determined using ROC curve analyzes (AUC = 0.868) with a sensitivity of 80.1% and a specificity of 78.2%. Patients with pulmonary TB also had higher titers of IgG (OD = 0.525 ± 0.391) than healthy controls (OD = 0.215 ± 0.077). The cutoff for IgG-ELISA was determined using ROC curve analyzes (AUC = 0.864) with a sensitivity of 81.7% and a specificity of 74.7%.

Conclusion: The results suggest that the recombinant protein CMX can be used in a serological test to complement the screening of individuals suspected of having active pulmonary TB.     

Pharmacokinetics and pharmacodynamics of the nucleoside sparing dual regimen containing rilpivirine plus darunavir/ritonavir in treatment-naïve HIV-1-infected individuals

Background: We aimed at investigating the antiviral activity and the pharmacokinetics of the dual antiretroviral (ARV) combination of rilpivirine plus darunavir/ritonavir 25/800/100 mg once-daily in naïve HIV-1-infected individuals (NHII) with different baseline viral loads.

Settings: Pharmacokinetic/pharmacodynamics study in ARV-naïve HIV-infected individuals.

Methods: The primary endpoint was the number of NHII with HIV-RNA < 40 copies/mL at week 48. Secondary endpoints included rilpivirine/darunavir/ritonavir pharmacokinetics, HIV-RNA decay, and changes in ECG QT interval.

Results: Thirty-six individuals were enrolled, 18 with a baseline viral load < 100,000 copies/mL (group A) and 18 with a baseline viral load > 100,000 copies/mL (group B). All but 1 (HIV-RNA = 63 copies/mL) subjects achieved viral load < 50 copies/mL by week 36, and all at week 48. Median (range) HIV-RNA reduction (Log10 copies/mL) was 1.3 (0.6–1.9) over the first week, with no differences between groups A and B. Geometric mean and 95%CI rilpivirine C_max, C_trough, AUC were 183 (165–239), 114 (104–109) ng/mL, 2966 (2704–3820) ng h/mL. No QTcF interval changes were recorded.

Conclusions: rilpivirine/darunavir/ritonavir could be efficacious, with limited short-term toxicity in ARV-naïve patients. Although rilpivirine was co-administered with ritonavir, its exposure was within ranges measured during phase III trials.     

Systematic overview of neuroanatomical differences in ADHD: Definitive evidence

Objectives: This article seeks to identify neuroanatomical differences in ADHD through an overview of systematic reviews that report encephalic differences compared to a control group in volume, area, activation likelihood or chemical composition.

Methods: We conducted a systematic search using Cochrane guidelines and PRISMA criteria in PubMed, Scopus, Web of Science, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects.

Results: Results revealed broad encephalic involvement that includes a functional frontal and cingulate hypoactivation and structural differences in corpus callosum, cerebellum and basal nuclei.

Conclusions: ADHD symptoms might be due to a multi-network unbalanced functioning hypothesis.     

Study of the osteoprotegerin/receptor activator of nuclear factor-kB ligand system association with inflammation and atherosclerosis in systemic sclerosis

Objective: we aimed to study systemic sclerosis patients in order to assess osteoprotegerin/Receptor activator of nuclear factor-kB ligand (OPG/RANKL) system and find the relation of these biomarkers with the clinical features of the disease, the carotid intima thickness, markers of inflammation, lipid profile, and other laboratory characteristics.

Methods: both the level of (RANKL), (OPG) in sera of participants, in 30 (SSc) patients and the atherosclerotic changes affecting the common carotid artery were measured and, were compared to 30 healthy controls matched for age and sex. All participants were assessed clinically and subjected to the Revised Medsger SSc severity scale and underwent carotid Doppler ultrasound examination.

Results: OPG, RANKL, and RANKL/OPG were 1.9 ± 0.4 ng/ml, 24.3 ± 17.25 ng/ml, and 13.5 ±9.8 versus 0.77 ± 0.25 ng/ml, 7.13 ± 3.02 ng/ml, and 9.6 ± 3.1 in the SSc patients and the controls with significance (P = 0.001, P = 0.001, P = 0.045) respectively. The OPG- RANKL axis in the SSc patients correlated significantly with carotid intima thickness, arthritis, arthralgia, inflammatory markers, Medsger joint, Medsger vascular, Medsger skin, and dyslipidemia.

Conclusion: In cardiovascular risks, OPG serum level might increase as a preventive compensatory mechanism to neutralize the RANKL level increment. The determination of the OPG-RANKL system is a diagnostic indicator for the intensity of vascular calcification and atherosclerosis in SSc patients.     

Biologic drugs in adult onset Still’s disease: a systematic review and meta-analysis of observational studies

Background: Biological drugs, mainly interleukin (IL)-1 and IL-6 antagonists, but also tumor necrosis factor (TNF) inhibitors, have been used in the treatment of adult onset Still’s disease patients (AOSD).

Methods: We summarised the available evidence for the effectiveness of biologic drugs in AOSD. A systematic review of the literature was performed in order to identify all the available data concerning the effectiveness of biologic drugs in AOSD. The proportion of patients achieving complete remission or any clinical response was calculated. The meta-analysis was thus performed using a random-effects model accounting for the expected high level of heterogeneity.

Results: Nineteen observational published studies were included in the meta-analysis. The pooled analysis under a random-effects model showed an overall rate of clinical response of 0.85 (95% CI: 0.77–0.91, p < 0.0001) and an overall rate of complete remission of 0.66 (95% CI: 0.54–0.77, p = 0.01). The heterogeneity across studies was high (Q = 59.82 with df = 19.0, p < 0.0001, I² = 68.23%).

Conclusions: Our meta-analysis suggests that AOSD patients may experience a clinical response and/or a complete remission when treated with biologic drugs. Specifically designed and powered studies are needed to fully investigate the role of such medications in the management of AOSD patients.     

Topical immunotherapy with diphencyprone (DPCP) for in-transit and unresectable cutaneous melanoma lesions: an inaugural Canadian series

Background: Diphencycprone (DPCP) is an immune contact sensitizer applied to melanoma lesions. Early studies show favorable efficacy. We present the first North-American series of patients treated with DPCP.

Methods: A single center retrospective study of patients with in-transit or unresectable melanoma lesions treated with DPCP from December 1,2014 to December 31,2015 was completed. Primary objectives were response rate and toxicity. Secondary objective was health-related quality of life assessment with the Functional Assessment of Cancer Therapy-Melanoma (FACT-M) questionnaire.

Results: Fifteen consecutive patients were identified with median age of 78 (range 43–92). 73% of patients had prior treatment. Two patients (13%) had a complete response after 25 and 32 weeks, respectively. Four patients (27%) had a partial response with a mean treatment time of 30 weeks (range 6–51 weeks). Six (40%) had stable disease. Six patients stopped DPCP – three from systemic progression and three from toxicity. The most common toxicity was blisters; one patient had significant skin ulceration that resolved on stopping DPCP. Median FACT-M score was 142.95 (possible total 172). Mean overall follow-up time was 22.7 weeks.

Conclusion: DPCP is a feasible option for in-transit and other melanoma cutaneous lesions ineligible/refractory to surgery and may delay need for systemic therapy.     

Update of sarilumb to treat rheumatoid arthritis based on randomized clinical trials: a systematic review

Introduction: Sarilumab is a human monoclonal antibody against Interleukin 6 α (IL-6α) receptor. Compared to tocilizumab, another IL-6 α receptor antibody, sarilumab has a different structure and higher affinity.

Areas covered: In a systematic literature review, we examined all sarilumab randomized clinical trials (RCTs) in rheumatoid arthritis. The 6 reviewed RCTs included patients who were inadequate MTX, DMARD and/or TNFi responders. Sarilumab 150–200 mg every 2 weeks improved RA signs, symptoms, function and decreased radiological progression up to 52 weeks. The most common adverse events were infections and neutropenia, the latter of which will require careful observation in future trials.

Examination of the effect of sero-positivity, disease duration, presence of erosions, use of previous biologic and comparisons to other biologics etc are still needed to complete understanding of this drug’s profile. Long term studies, too, will be needed to assess long term tolerability

Expert commentary: Results support the use of sarilumab to treat RA patients with inadequate response to MTX, other DMARDs and TNFis, although further studies are needed to fully assess its toxicity and understand the specific place of sarilumab in the RA armamentarium.     

Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relationship with clinical activity

Objective: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals.

Methods: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls.

Results: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04–2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades.

Conclusion: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.     

Efficacy and safety of emtricitabine/tenofovir alafenamide (FTC/TAF) vs. emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as a backbone for treatment of HIV-1 infection in virologically suppressed adults: subgroup analysis by third agent of a randomized,double-blind,active-controlled phase 3 trial*

Background: FTC/TAF was shown to be noninferior to FTC/TDF with advantages in markers of renal and bone safety.

Objective: To evaluate the efficacy and safety of switching to FTC/TAF from FTC/TDF by third agent (boosted protease inhibitor [PI] vs. unboosted third agent).

Methods: We conducted a 48-week subgroup analysis based on third agent from a randomized, double blind study in virologically suppressed adults on a FTC/TDF-containing regimen who switched to FTC/TAF vs. continued FTC/TDF while remaining on the same third agent.

Results: We randomized (1:1) 663 participants to either switch to FTC/TAF (N = 333) or continue FTC/TDF (N = 330), each with baseline third agent stratifying by class of third agent in the prior treatment regimen (boosted PI 46%, unboosted third agent 54%). At week 48, significant differences in renal biomarkers and bone mineral density were observed favoring FTC/TAF over FTC/TDF (p < 0.05 for all), with similar improvements in the FTC/TAF arm in those who received boosted PI vs. unboosted third agents. At week 48, virologic success rates were similar between treatment groups for those who received a boosted PI (FTC/TAF 92%, FTC/TDF 93%) and for those who received an unboosted third agent (97% vs. 93%).

Conclusions: In virologically suppressed patients switching to FTC/TAF from FTC/TDF, high rates of virologic suppression were maintained, while renal and bone safety parameters improved, regardless of whether participants were receiving a boosted PI or an unboosted third agent. FTC/TAF offers safety advantages over FTC/TDF and can be an important option as an NRTI backbone given with a variety of third agents.     

An observational study on the incidence of tuberculosis among a cohort of HIV infected adults in a setting with low prevalence of tuberculosis

Background: Tuberculosis (TB) remains a main cause of morbidity and mortality among individuals infected with HIV. We investigated the incidence of TB among a cohort of HIV infected patients attending a setting with low TB burden where screening for latent TB infection is not routinely carried out.

Methods: an observational cohort study on HIV-infected adults attending the HIV clinic at Queen Elizabeth Hospital Birmingham, UK between 1 January 2011 and 30 September 2015. Patients with culture-proven TB after HIV diagnosis, or those treated for clinical diagnosis of the infection, were classified as having “active TB”.

Results: 1824 patients were included in the study (5347 patient years of follow up), of whom 21 patients developed TB (16 microbiology confirmed). Of the 666 new HIV diagnoses, six patients developed TB within one month, giving a TB prevalence at the time of HIV diagnosis of 0.9%. The total TB incidence for the remaining 1818 patients was 2.81 cases per 1000 patient years (95% CI: 1.63–4.53). TB incidence was significantly more common among patients with CD4 ≤ 200 cells/mm³ compared to those with CD4 > 500 cells/mm³ (28.2 vs. 1.22 per 1000 patient years, p < 0.001), and in patients with VL ≥ 40 copies/mL compared to <40 copies/mL (8.30 vs. 1.42, p < 0.001).

Conclusion: In settings with low TB prevalence, early start of combined antiretroviral therapy and intensified TB case finding protocols may significantly reduce the incidence of TB.