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.     

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.     

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.     

Diverticulosis and nine connective tissue disorders: epidemiological support for an association

Purpose: An underlying connective tissue disorder (CTD) may predispose to formation of intestinal diverticula. We assess the association of diverticulosis with nine selected CTDs, to inform the pathophysiology of diverticula.

Methods: A population-based period-prevalence study. Individuals (3.5 million New Zealand residents born 1901–1986) with a health system record 1999–2016 were grouped into those with a hospital diagnosis of diverticulosis or diverticulitis (ICD-10-AM K57), and those without. Also recorded were any hospital diagnoses of nine selected CTDs. The association of exposure to diverticulosis and each CTD was assessed using logistic regressions adjusted for age, gender, ethnicity and region.

Results: In all, 85,958 (2.4%) people had a hospital diagnosis of diverticulosis. Hospitalisation with diverticulosis was highly significantly associated with rectal prolapse (adjusted odds ratio [OR] = 3.9), polycystic kidney disease (OR = 3.8), heritable syndromes (Marfan or Ehlers-Danlos) (OR = 2.4), female genital prolapse (OR = 2.3), non-aortic aneurysm (OR = 2.3), aortic aneurysm (OR = 2.2), inguinal hernia (OR = 1.9) and dislocations of shoulder and other joints (OR = 1.7), but not subarachnoid haemorrhage (OR = 1.0).

Conclusion: People with diverticulosis are more likely to have colonic extracellular matrix (ECM)/connective tissue alterations in anatomical areas other than the bowel, suggesting linked ECM/connective tissue pathology. Although biases may exist, the results indicate large-scale integrated studies are needed to investigate underlying genetic pathophysiology of colonic diverticula, together with fundamental biological studies to investigate cellular phenotypes and ECM changes.     

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.     

Complex role of IL-23R polymorphisms on ankylosing spondylitis: a meta-analysis

Background: The aim of the meta-analysis was to evaluate the association between 10 widely studied polymorphisms of interleukin-23 receptor gene (IL-23R) and ankylosing spondylitis (AS).

Methods: A comprehensive literature search, screening of eligible articles and data extraction was performed independently by two investigators. Further meta-analysis was conducted with STATA 12.0 software (Stata Corp.; College Station, TX, USA). The association between IL-23R polymorphisms and AS was evaluated by odds ratio (OR) and 95% confidence intervals (95% CI).

Results: Twenty-five case–control studies with 8431 cases and 8972 controls were included in this meta-analysis. Quantitative meta-analysis revealed that minor allele frequency (MAF) of rs1004819, rs1495965, and rs2201841 was significantly higher in the AS group (p value < .001, < .001, = .010, respectively). MAF of rs10489629, rs11209026, rs11465804, and rs1343151was significantly lower in the AS group (p value = .002, < .001, = .032, < .001, respectively). However, there is no significant difference between these two groups in rs10889677, rs11209032, and rs7517847 frequency (p value = .128, .237, .131, respectively).

Conclusions: The present study indicates that minor allele carriers of rs1004819, rs1495965, and rs2201841 are susceptible to AS. Conversely, minor alleles of rs10489629, rs11209026, rs11465804, and rs1343151 have protective effect on AS.     

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.     

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.     

Analysis of Helios gene expression and Foxp3 TSDR methylation in the newly diagnosed Rheumatoid Arthritis patients

Background: The control of auto-reactive cells is defective in rheumatoid arthritis (RA). Regulatory T (Treg) cells which play a key role in the modulation of immune responses have an impaired function in RA. Foxp3 is a master regulator of Treg cells which its expression is under the tight control of epigenetic mechanisms. In the current study, we analyzed the epigenetic modulation of the Foxp3 Treg-specific demethylated region (TSDR) and Helios gene expression to determine Treg cells alteration in RA patients.

Methods: We have recruited 20 newly diagnosed patients with RA and 41 healthy controls in our study. The measurement of Foxp3 and Helios gene expression was performed by the real-time PCR technique and the methylation level of TSDR was analyzed by bisulfite treatment and quantitative methylation-specific PCR (Q-MSP).

Results: We found that RA patients had significantly lower level of Foxp3 gene expression and TSDR demethylation compared to healthy subjects (P < 0.001 and P = 0.006, respectively). Inversely, the Helios gene expression was elevated significantly in RA patients group (P = 0.048). We also observed a significant correlation between Foxp3 and Helios gene expression (P = 0.016) as well as a significant correlation between FoxP3 expression and demethylation rate of TSDR (P = 0.010).

Conclusion: Our results suggested that both epigenetic modifications and Helios gene expression may have important roles in the pathogenesis of RA through their effects on Foxp3 gene expression.     

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.     

The HIV Care Cascade and sub-analysis of those linked to but not retained in care: the experience from a tertiary HIV referral service in Dublin Ireland

Background: The HIV Care Cascade model can be used to measure how clinical services align with United Nations’ (UN) HIV treatment targets. Previous models have highlighted sequential losses at each step of the Cascade with a significant proportion being not retained in care (NRIC).

Objective: We aimed to assess the feasibility of meeting the UN targets and assess factors associated with, and calculate the true proportion of those, NRIC.

Methods: All people living with HIV who were linked to our service, one of three specialist HIV care providers in Dublin Ireland, from its establishment in 1993 to 1 December 2014, were included in the cohort and were categorized as linked to care, retained in care (RIC), on antiretroviral therapy (on ART), virally suppressed (HIV RNA <40copies/ml), and NRIC. An analysis of those NRIC was performed to categorize their current status through direct/indirect contact.

Results: Of 1000 patients linked to care, 78.7% (n = 787) were RIC, of whom 91.5% (n = 720) were on ART, with 89.9% (n = 644) virally suppressed. Those RIC were more likely older (p = 0.006) and non-IVDU (p < 0.001). Of 213 (21.3%) NRIC, 56 (26.3%) emigrated, 27 (12.7%) transferred care, 15 (7.0%) stopped attending but were contactable, 38 (17.8%) died, and 77 (36.1%) were lost to follow-up. After revision, 10.5% of the cohort was confirmed as NRIC, with 6 of 15 defined as “stopped attending” re-linked to care following direct contact.

Conclusions: Our HIV Care Cascade model demonstrates that the true numbers of patients NRIC may be significantly lower than previously estimated and once RIC, treatment goals approaching the United Nations Programme on HIV and AIDS targets are possible with 91.5% on treatment and almost 90% of those on treatment virally suppressed. That 40% reengaged following direct contact suggests benefit through regular monitoring and direct contact based on the HIV Care Cascade model.     

Th17-Inducing Conditions Lead to in vitro Activation of Both Th17 and Th1 Responses in Behcet’s Disease

Objectives: Interleukin-17 (IL-17) has been associated with the pathogenesis of various autoimmune/inflammatory diseases. The aim of this study was to investigate the expression of Th17-related immunity in an innate immunity-dominated vasculitis, namely Behcet’s disease (BD).

Methods: Peripheral blood mononuclear cells from 37 patients (age: 38.5 ± 9.8 years) with BD, and 25 healthy controls (HC) (age: 39.1 ± 9.3 years), were cultured in Th17-inducing conditions (IL-6, Phytohemagglutinin (PHA), IL-1β, and IL-23) for 6 days. Cultured cells were stained with CD4, CD8, CD3, TCR gamma/delta, CD19, interferon-γ (IFN-γ), and IL-17 antibodies to determine the intracellular cytokine secretion by flow cytometry.

Results: IL-17 expression by CD8+ and γδ+ T cells was higher in BD compared to HC (p = 0.004, p = 0.003, respectively). No differences were observed between the groups in the IL-17 production by B cells. Under Th17-inducing conditions, production of IFN-γ by CD4+, CD8+, and γδ+ T cells was also higher in BD compared to HC (p < 0.05 in all).

Conclusion: Our results suggest that under Th17-stimulating conditions, T cells express both IL-17 and IFN-γ in BD. More prominent IL-17 and IFN-γ production by all lymphocyte subsets in BD might be associated with the increased innate responses, early tissue neutrophil infiltrations and late adaptive immunity in BD.     

Associations between vitamin D receptor polymorphisms and susceptibility to Behcet’s disease: A meta-analysis

Background: The vitamin D receptor (VDR) gene polymorphisms have been reported to be related to the development of Behcet’s disease (BD). However, the results have been inconsistent among diverse populations. Therefore, this comprehensive meta-analysis has been designed to assess a more accurate association between VDR polymorphisms and BD susceptibility.

Methods: An electronic literature search was conducted to identify eligible studies. Pooled odds ratios (OR) with corresponding 95% confidence interval (CI) were calculated in different genetic models to assess this association.

Results: A total of six separate comparisons comprised of 468 cases and 516 controls were included in the meta-analysis model. The meta-result demonstrated that A allele of ApaI (A vs. a: 1.54 95% CI = 1.04–2.26, P = 0.029), and F allele of FokI (F vs. f: OR = 0.58, 95% CI = 0.45–0.76, P = 0.007) polymorphisms were associated with the risk of BD in total and African populations, respectively. This significant association was also found in recessive and homozygotes models. Subgroup analysis indicated that FokI variant among Africans and ApaI variant among Caucasian were significantly associated with the risk of BD. No relationship was found between Bsmi and TaqI polymorphisms and BD risk.

Conclusion: This meta-analysis demonstrated the association between FokI and ApaI polymorphisms in VDR gene with the risk of BD, providing insights into the potential role of vitamin D receptor in the pathogenesis of BD.     

Interleukin-4 Gene Intron 3 VNTR Polymorphism in Type 2 Diabetes Patients with Peripheral Neuropathy

Objective: Diabetic peripheral neuropathy (DPN) is one of late complications of diabetes mellitus. The aim of this study was to evaluate the association between variable number tandem repeat (VNTR) polymorphism in intron 3 of interleukin-4 gene and risk of DPN.

Methods: We examined 926 T2DM patients and 420 healthy controls. In the patient group, 44% had DPN. Genomic DNA was isolated from all subjects and genotyped for the IL-4 VNTR polymorphism by polymerase chain reaction (PCR).

Results: No significant difference was observed in the frequency of minor P1 allele between T2DM patients and controls (OR 1.00, 95% CI 0.81–1.23, p = 0.988). The distribution of IL-4 VNTR polymorphism was compared between patients with DPN and those without it. The polymorphism was not significantly associated with DPN in studied subjects. In comparison of 406 T2DM patients with DPN and 520 patients without it, the OR (95% CI) for P1 allele was 0.82 (0.65–1.04), p = 0.10 and for P1P1 genotype 1.00 (0.53–1.89), p = 0.991. When two subgroups of patients with DPN, those with cardiovascular disease (CVD) and without CVD, were compared, subgroup with coexisting CVD had significantly higher frequency of P1 allele than patients without CVD, with odds ratio for the P1 allele 3.27 (95% CI 1.83–5.83), p = 0.0001.

Conclusion: Our results demonstrated that VNTR polymorphism in the IL-4 gene is associated with DPN in type 2 diabetes patients with coexisting CVD.     

Reduced Plasma Levels of sCD14 and I-FABP in HIV-infected Patients with Mesalazine-treated Ulcerative Colitis

Background: Microbial translocation (MT) is a shared feature of HIV infection and inflammatory bowel disease (IBD). Aims: This study was conducted to assess the impact of IBD (and particularly ulcerative colitis, UC) on plasma markers of MT and immune activation in HIV+ subjects.

Methods: A cross-sectional study was conducted in 3 groups of patients: HIV+/UC+(group HIV/UC); HIV+/UC- (group HIV); HIV-/UC+(group UC). Plasma levels of soluble CD14 (sCD14), intestinal fatty acid-binding protein (I-FABP), and endotoxin core antibodies (endoCAB) were measured as plasma markers of MT. Inflammation and immune activation were evaluated by measuring plasma levels of IL-6, IL-21, TNF-alpha, and high-sensitivity C-reactive protein (hs-CRP). T- and B-cells subpopulations were characterized by FACS analysis.

Results: Seven patients were enrolled in group HIV/UC, 9 in HIV, and 10 in UC. All HIV-positive patients had plasma values of HIV-1 RNA < 37 copies/mL for at least 12 months and good immunological recovery. All patients with UC were treated with oral mesalazine. Markers of MT, immune activation, and inflammation were not increased in subjects with HIV/UC. In fact, they had lower levels of I-FABP (p = 0.001) and sCD14 (p = 0.007) when compared to other patients groups. Positive correlations were found between I-FABP and sCD14 (r = .355, p = 0.076). Frequency of T- and B-cell subsets did not differ among groups.

Conclusions: Our results suggest that UC does not worsen MT, inflammation, or immune activation in HIV-infected subjects. The anti-inflammatory activity of chronic mesalazine administration on intestinal mucosa may contribute to this finding.     

The Potential Role of PTPN-22 C1858T Gene Polymorphism in the Pathogenesis of Type 1 Diabetes in Saudi Population

Background: Recent investigations have reported an association between protein tyrosine phosphatase non-receptor type-22 (PTPN-22) gene polymorphism and susceptibility to the development of type 1 diabetes (T1D) in some populations and not in others. In this study, we aimed to investigate the association of PTPN-22 C1858T polymorphism with T1D in Saudi children.

Methods: A cohort of 372 type 1 diabetic children and 372 diabetes-free subjects was enrolled in the current investigation. The PTPN-22 C1858T polymorphism was identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: Our data showed that the frequency of CT and TT genotypes of PTPN-22 C1858T was higher in T1D children (17.7% and 4.3%, respectively) compared to healthy controls (4.8% and 1.6%, respectively), and both genotypes were statistically associated with T1D patients (OR = 4.4, 95% CI: 2.55–7.58, p < 0.001; and OR = 3.2, 95% CI: 1.23–8.28, p = 0.017, respectively). Moreover, the 1858T allele was significantly associated with T1D patients compared to the C allele (OR = 3.2, 95% CI: 1.59–6.88, p < 0.001). In addition, the T allele was significantly associated with elevated levels of HbA1c, anti-GAD, and anti-insulin antibodies (p < 0.001) and a lower concentration of C-peptide (p < 0.001) in T1D children.

Conclusion: The data presented here suggests that the T allele of PTPN-22 C1858T polymorphism might be a risk factor for T1D development in Saudi children.