Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in Korean patients with adult-onset Still's disease

OBJECTIVE: Interleukin-1 (IL-1) has been implicated in the pathogenesis of several rheumatic inflammatory diseases, including adult-onset Still's disease (AOSD) and systemic-onset juvenile idiopathic arthritis (SoJIA). Several clinical trials also suggest that anakinra, a human recombinant interleukin-1 receptor antagonist (IL-1Ra), is effective in patients with AOSD and SoJIA. We have therefore investigated whether IL-1beta and IL-1Ra gene polymorphisms are associated with the development and clinical features of AOSD. METHODS: Genomic DNA was isolated from 83 AOSD patients and 144 healthy controls. Genotyping of the two IL-1beta gene (IL-1B+3954 and IL-1B-511) polymorphisms was performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Genotyping of the IL-1Ra gene (intron 2, VNTR) polymorphism was performed using PCR-based analysis. To compare genotype and allele frequencies, the chi2-test or Fisher's exact test was used. Haplotype frequencies and pairwise linkage disequilibrium were also estimated. A p-value <0.05 was considered significant. RESULTS: There were no significant differences in the genotype and allele frequencies of the IL-1beta and IL-1Ra gene polymorphisms. No differences were also found in the IL-1 gene cluster haplotypes between both groups. IL-1 gene cluster polymorphisms had no effect on the clinical course and joint involvement pattern. Nevertheless, the IL-1B-511 and IL-1RN (VNTR) polymorphic sites were in linkage disequilibrium. CONCLUSION: These results suggest that IL-1beta and IL-1Ra gene polymorphisms are not associated with the development and clinical features of AOSD in Korean patients.     

心力衰竭患者血清CA125、CA19-9水平变化及意义

目的探讨慢性心衰(CHF)患者血清CA125、CA19-9水平变化及意义。方法(1)研究对象与分组:心衰组(CHF),按AHA指南标准随机人选17例慢性心衰患者,心功能Ⅱ-Ⅳ级(NY-HA),年龄36-86(51.7±13.2)岁。其中风湿性心脏病4例,高血压6例,冠心病5例,贫血性心脏病1例,其他1例;在这17例病例中合并心包积液2例、胸腔积液1例、心房纤颤3例,左心房及静脉血栓1例;非心衰组(NHF),冠心病(非心衰者)、高血压Ⅰ期患者13例,年龄21-77岁,健康对照组(Control),健康成年人15例,年龄25-73岁;(2)CA125、CA19-9测定:抽取清晨空腹静脉血5ml,化学发光免疫法测定血清CA125、CA19-9水平。同时,检测肿瘤三项(CEA、AFP、SF)、胸片、头颅CT以及腹部、盆腔超声,排外潜在的肿瘤;(3)统计学分析:数据采用均数±标准差(x±s)表示,t检验,P<0.05有统计学意义。结果与非心衰组和健康对照组比较,心衰组血清CA125显著升高,且与心衰严重程度(Ⅱ、Ⅲ、Ⅳ级)相关(分别P<0.01,P<0.001,P<0.001);非心衰组与健康对照组比较,无显著差别(P>0.05)。然而,各组间CA19-9水平无显著变化(P>0.05)。同时,发现合并心包、胸腔积液,尤其慢性房颤者,CA125显著升高。结论CA125是诊断和评价慢性心衰的一个良好指标,且与心衰程度相关,而CA19-9与心衰无明显关系。     

Primary drug resistance and transmission analysis of HIV-1 in acute and recent drug-naïve seroconverters in Singapore

Objectives

The aim of the study was to elucidate primary drug resistance and transmission of HIV‐1 in acute and recent drug‐naïve seroconverters in Singapore.

Methods

Acute and recent HIV‐1 seroconverters were enrolled in the study. The HIV‐1 polymerase (pol) gene was sequenced and used for genotypic drug resistance analysis and phylogenetic analysis. HIV‐1 transmission clusters were inferred from phylogenetic clustering analysis.

Results

Of the 60 subjects analysed, 95% were men, and 73.3% were men who have sex with men (MSM). Six HIV‐1 subtypes were identified, including CRF01_AE (46.7%), subtypes B (30%), B′ (15%) and G (1.7%), CRF33_01B (1.7%) and CRF34_01B (5%). Primary genotypic resistance was detected in only one (1.7%) subtype B variant. Thirty‐one patients (51.7%) were phylogenetically clustered, of whom 90% reported having local risk exposure, compared with 59% of the patients who were not phylogenetically clustered [odds ratio (OR) 6.35, 95% confidence interval (CI) 1.65–23.95]. MSM (OR 5.63, 95% CI 1.17–27.15), high viral load (OR 4.28, 95% CI 1.37–13.36) and young age (OR 0.92, 95% CI 0.85–0.99) were independently associated with clustered individuals.

Conclusions

In Singapore, HIV‐1 primary resistance is insignificant; individuals with seroconversion account for about half of onward transmission among recently infected seroconverters. MSM, high viral load and young age are factors that facilitate transmission. Early detection of these individuals is of paramount importance for the prevention of HIV‐1 transmission.

     

Community Sexual Bridging Among Heterosexuals at High-Risk of HIV in New York City

Community sexual bridging may influence the socio-geographic distribution of heterosexually transmitted HIV. In a cross-sectional study, heterosexual adults at high-risk of HIV were recruited in New York City (NYC) in 2010 for the Centers for Disease Control and Prevention-sponsored National HIV Behavioral Surveillance system. Eligible participants were interviewed about their HIV risk behaviors and sexual partnerships and tested for HIV. Social network analysis of the geographic location of participants’ recent sexual partnerships was used to calculate three sexual bridging measures (non-redundant ties, flow-betweenness and walk-betweenness) for NYC communities (defined as United Hospital Fund neighborhoods), which were plotted against HIV prevalence in each community. The analysis sample comprised 494 participants and 1534 sexual partnerships. Participants were 60.1 % male, 79.6 % non-Hispanic black and 19.6 % Hispanic race/ethnicity; the median age was 40 years (IQR 24–50); 37.7 % had ever been homeless (past 12 months); 16.6 % had ever injected drugs; in the past 12 months 76.7 % used non-injection drugs and 90.1 % engaged in condomless vaginal or anal sex; 9.6 % tested HIV positive (of 481 with positive/negative results). Sexual partnerships were located in 33 (78.6 %) of 42 NYC communities, including 13 “high HIV-spread communities”, 7 “hidden bridging communities”, 0 “contained high HIV prevalence communities”, and 13 “latent HIV bridging communities”. Compared with latent HIV bridging communities, the population racial/ethnic composition was more likely (p < 0.0001) to be black or Hispanic in high HIV-spread communities and to be black in hidden bridging communities. High HIV-spread and hidden bridging communities may facilitate the maintenance and spread of heterosexually transmitted HIV in black and Hispanic populations in NYC.     

Depressed functional and phenotypic properties of T but not B lymphocytes in idiopathic thrombocytopenic purpura

Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which the abnormality in cellular immunity has remained only vaguely defined. Previously we have shown that patients with ITP in its active phase have abnormal T cell subsets. We then examined the phenotypes of T and B lymphocytes in an additional 28 patients with ITP and 32 age- and sex-matched normal controls and compared the lymphocytes' capacity to respond to polyclonal T, T cell-dependent B, and B cell mitogens. Blastogenesis to optimal (5.0 micrograms/mL) and suboptimal (0.5 microgram/mL) concentrations of the polyclonal T cell mitogens were markedly depressed in patients compared with normal controls (P less than .0005). Similarly, a severe depression in response was noted with the polyclonal T cell-dependent B cell mitogen (P less than .000001). No difference was seen, however, with the polyclonal B cell mitogen. The proportions of pan-T and T helper/inducer lymphocytes were significantly depressed (P less than .005 and P less than .000005 respectively), and the T suppressor/cytotoxic lymphocytes increased (P less than .02) in patients relative to controls. But there was no difference in the proportion of B lymphocytes or in their functional response. The abnormal cellular immunity appears to be due to a defect in the T lymphocyte population without involvement of the B lymphocytes.     

A review of the radiological features of intracranial meningiomas

To evaluate the role of radiological imaging of meningiomas in confirming the diagnosis and as a neuroanatomical aid to surgical planning, 115 patients with surgically excised meningiomas between 1990 and 1993 were studied. Computed tomography (CT), magnetic resonance imaging (MRI) (on a 0.5T unit) and angiography were reviewed, and compared with histopathology (when available). Seventy-eight CT, 89 MRI and 85 angiographic studies were reviewed, and correlated with histopathology in 67 cases. In 48 cases, the surgical specimens could not be pathologically classified. The most common lesion sites were the cerebral convexities, falx and sphenoidal ridges. True demarcation of cleavage planes was seen on 73% of MRI and 10% of CT studies. Computed tomography showed hyperostosis in 27% and MRI in 7% of studies. Tumours enhanced strongly with contrast in 98% of CT scans. On MRI there were variable signal intensities on different sequences, and no correlation between signal intensities and histological subtype was found. Oedema was present in 59% of CT and 66% of MRI studies, and was most pronounced in lesions > 3 cm in diameter. Tumour calcification was seen in 62% of CT and 8% of MRI studies. Vascular abnormalities were seen on 65% of MRI, 21% of CT and 84% of angiogram studies. Angiographic tumour vascularity did not correlate with histologic subtype. All three imaging modalities have management roles: CT for bony changes and calcification, MRI for multiplanar and vessel anatomy imaging, and angiography for vessel delineation and embolization if required.     

Subchondral Calcium Phosphate is Ineffective for Bone Marrow Edema Lesions in Adults With Advanced Osteoarthritis

Background

Injury to subchondral bone is associated with knee pain and osteoarthritis (OA). A percutaneous calcium phosphate injection is a novel approach in which subchondral bone marrow edema lesions are percutaneously injected with calcium phosphate. In theory, calcium phosphate provides structural support while it is gradually replaced by bone. However, little clinical evidence supports the efficacy of percutaneous calcium phosphate injections.

Questions/purposes

We asked: (1) Does percutaneous calcium phosphate injection improve validated patient-reported outcome measures? (2) What proportion of patients experience failure of treatment (defined as a low score on the Tegner Lysholm Knee Scoring Scale)? (3) Is there a relationship between outcome and age, sex, BMI, and preoperative grade of OA?

Methods

Between September 2012 and January 2014, we treated 33 patients with percutaneous calcium phosphate injections. Twenty-five satisfied our study inclusion criteria; of those, three patients were lost to followup and 22 (88%; 13 men, nine women) with a median age of 53.5 years (range, 38–70 years) were available for retrospective chart review and telephone evaluation at a minimum of 6 months (median, 12 months; range, 6–24 months). Our general indications for this procedure were the presence of subchondral bone marrow edema lesions observed on MR images involving weightbearing regions of the knee associated with localized pain on weightbearing and palpation and failure to respond to conservative therapy (> 3 months). Patients with pain secondary to extensive nondegenerative meniscal tears with a flipped displaced component at the level of bone marrow edema lesions, or with mechanical axis deviation greater than 8° were excluded. All patients had Grades III or IV chondral lesions (modified Outerbridge grading system for chondromalacia) overlying MRI-identified subchondral bone marrow edema lesions. Percutaneous calcium phosphate injection was performed on the medial tibial condyle (15 patients), the medial femoral condyle (five patients), and the lateral femoral condyle (two patients). Concomitant partial meniscectomy was performed in 18 patients. Preoperative and postoperative scores from the Knee Injury and Arthritis Outcome Score (KOOS) and the Tegner Lysholm Knee Scoring Scale were analyzed.

Results

For patients available for followup, the outcome scores improved after treatment. The KOOS improved from a mean of 39.5 ± 21.8 to 71.3 ± 23 (95% CI, 18.6–45.2; p < 0.001) and the Tegner and Lysholm score from 48 ± 15.1 to 77.5 ± 20.6 (95% CI, 18.8–40.2; p < 0.001). However, seven of the 22 patients had poor clinical outcomes as assessed by the Tegner Lysholm Knee Scoring Scale, whereas three had fair results, five had good results, and seven had excellent results. The postoperative Tegner Lysholm score was inversely related to the preoperative Kellgren-Lawrence OA grade (R² = 0.292; F (1.20) = 9.645; p = 0.006). We found no relationship between outcome scores and age, sex, or BMI.

Conclusions

In a study that would have been expected to present a best-case analysis (short-term followup, loss to followup of patients with potentially unsatisfactory results, and use of invasive cotreatments including arthroscopic débridements), we found that percutaneous calcium phosphate injection in patients with symptomatic bone marrow edema lesions of the knee and advanced OA yielded poor results in a concerning proportion of our patients. Based on these results, we advise against the use of percutaneous calcium phosphate injections for patients with advanced osteoarthritic changes.

Level of Evidence

Level IV, therapeutic study.     

Posterolateral corner injuries of the knee

The posterolateral region of the knee is an anatomically complex area that plays an important role in the stabilization of the knee relative to specific force vectors at low angles of knee flexion. A renewed interest in this region and advanced biomechanical studies have brought additional understanding of both the anatomy and the function of posterolateral structures in knee stabilization and kinematics. Through sectioning and loading studies, the posterolateral corner has been shown to play a role in the prevention of varus angulation, external rotation, and posterior translation. The potential for long-term disability from these injuries may be related to increased articular pressure and chondral degeneration. The failure of the reconstruction of cruciate ligaments may be due to unrecognized or untreated posterolateral corner injuries. Various methods of repair and reconstruction have been described and new research is yielding superior results from reconstruction of this region.