Association of interleukin-6 and interleukin-18 with cardiovascular disease in older adults: Atherosclerosis Risk in Communities study.

AIMS: Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global cardiovascular disease (CVD), atrial fibrillation (AF), and death in older adults. METHODS AND RESULTS: Participants from Atherosclerosis Risk in Communities study Visit 5 (mean age 75.4 ± 5.1 years) with IL-6 and IL-18 measurements were included (n = 5672). Cox regression models were used to assess associations of IL-6 and IL-18 with coronary heart disease (CHD), ischaemic stroke, heart failure (HF) hospitalization, global CVD (composite of CHD, stroke, and HF), AF, and all-cause death. Over a median follow-up of 7.2 years, there were 1235 global CVD events, 530 AF events, and 1173 deaths. Higher IL-6 [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.44-1.72 per log unit increase] and IL-18 (HR 1.13, 95% CI 1.01-1.26) were significantly associated with global CVD after adjustment for cardiovascular risk factors. Association between IL-6 and global CVD remained significant after further adjustment for high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT) but was no longer significant for IL-18 after further adjustments. Interleukin-6 was also associated with increased risk for CHD, HF, and AF after adjustment for covariates. Both IL-6 and IL-18 were associated with increased risk for all-cause death independent of cardiovascular risk factors and other biomarkers. CONCLUSION: Among older adults, both IL-6 and IL-18 were associated with global CVD and death. The association between IL-6 with CVD appears to be more robust and was independent of hs-CRP, NT-proBNP, and hs-TnT.

In older adults in the Atherosclerosis Risk in Communities study (average age 75 years), higher levels of interleukin-6 and interleukin-18, two proteins implicated in atherosclerosis and increased inflammation that occurs with ageing, significantly increased risk for global cardiovascular disease (including coronary heart disease, stroke, and heart failure) during the next ∼7 years; interleukin-6 also increased risk for global cardiovascular disease, coronary heart disease, heart failure, and atrial fibrillation even after adjustment for other biomarkers of inflammation and subclinical myocardial injury, and both interleukin-6 and interleukin-18 were associated with increased risk for all-cause death independent of cardiovascular risk factors and other biomarkers. In older adults, higher levels of interleukin-6 and interleukin-18 were both associated with increased risk for global cardiovascular disease (including coronary heart disease, stroke, and heart failure) and death.The association between interleukin-6 and global cardiovascular disease appeared to be stronger than that for interleukin-18 and remained significant after adjustment for other biomarkers of inflammation and subclinical myocardial injury.

Heterogeneity in the prevalence of premature hypertension among Asian American populations compared with white individuals: A National Health Interview Survey study.

Background: Differences in prevalence of risk factors such as hypertension may explain heterogeneity in cardiovascular risk across Asian American populations. Methods: We used National Health Interview Survey (NHIS) data from 2006 to 2018 among White, Chinese, Asian Indian, Filipino, and 'other Asians' (Japanese, Korean, and Vietnamese). Unadjusted and adjusted odds ratios (aOR) with 95% confidence intervals were reported using logistic regression models for the association between race and self-reported premature hypertension (age <50 years old). Models were adjusted for sex, education, body mass index, smoking status, diabetes, and coronary heart disease. Results: We studied 99,864 participants with history of hypertension (mean age, 59.3 ± 0.1; 50% women, 90% US born). Asian Indians had higher prevalence of premature hypertension (37%) compared with Filipinos (27%), 'other Asians' (26%), Whites (25%), and Chinese (21%). Compared with Whites, Chinese individuals had lower odds of premature hypertension (aOR = 0.79, 0.63-0.98), but Asian Indians had higher odds (aOR = 1.85, 1.48-2.31). Compared with Chinese, odds of premature hypertension was higher for Asian Indians (aOR = 2.39, 1.74-3.27), Filipinos (aOR = 1.53, 1.16-2.04), and 'other Asians' (OR = 1.32, 1.03-1.70; aOR = 1.59, 1.20-2.10). Overall prevalence of hypertension was lower among Asian Indians (aOR = 0.52, 0.46-0.58) and 'other Asians' (aOR = 0.74, 0.68-0.79) compared with Whites. Conclusions: There is heterogeneity in the risk of hypertension across Asian Americans by age. Asian Indians and 'other Asians' had higher prevalence of premature hypertension and lower prevalence of overall hypertension, which may call for earlier screening for risk factors among these populations.

Social Determinants of Health and Comorbidities Among Individuals with Atherosclerotic Cardiovascular Disease: The Behavioral Risk Factor Surveillance System Survey.

Individuals with atherosclerotic cardiovascular disease (ASCVD) often have a high burden of comorbidities. Social determinants of health (SDOH) may complicate adherence to treatment in these patients. This study assessed the association of comorbidities and SDOH among individuals with ASCVD. Cross-sectional data from the 2016 to 2019 Behavioral Risk Factor Surveillance System, a nationally representative US telephone-based survey of adults ages ≥18 years, were used. Cardiovascular comorbidities included hypertension, hyperlipidemia, diabetes mellitus, current cigarette smoking, and chronic kidney disease. Non-cardiovascular comorbidities included chronic obstructive pulmonary disease, asthma, arthritis, cancer, and depression. SDOH associated with being at or above the 75th percentile of comorbidity burden were analyzed using multivariable adjusted logistic regression models. The study population included 387,044 individuals, 9% of whom had ASCVD. The mean (SD) numbers of total, cardiovascular, and non-cardiovascular comorbidities were 1.97 (1.27), 1.28 (0.74), 0.69 (0.91) among those without ASCVD and 3.28 (1.62), 1.73 (0.91), and 1.54 (1.22) among those with ASCVD, respectively (P < 0.001 for all comparisons). Female gender, household income ≤$75,000, being unemployed, and difficulty accessing health care were significantly associated with a higher burden of comorbidities among those with ASCVD. The mean (SD) numbers of comorbidities for those with 0, 1, 2, and ≥3 of the aforementioned SDOH were 2.89 (1.45), 2.86 (1.47), 3.39 (1.58), and 4.01 (1.73), respectively (P < 0.001). Among persons with ASCVD, the burden of cardiovascular and non-cardiovascular comorbidities is directly proportional to SDOH in any given individual. Clinicians should address SDOH when managing high-risk individuals.

Association between circulating Galectin-3 and arterial stiffness in older adults.

Background: Galectin-3 (gal-3) is a ß-galactoside-binding lectin associated tissue fibrosis and inflammation. There is limited understanding of the relationship between gal-3 and vascular health. Our aim was to assess the association between gal-3 and arterial stiffness in older adults. Methods: We conducted a cross-sectional study of 4275 participants (mean age of 75 years) from the Atherosclerosis Risk in Communities (ARIC) Study. Central arterial stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). We evaluated the association of gal-3 with cfPWV using multivariable linear regression. Results: The median (interquartile range) gal-3 concentration was 16.5 (13.8, 19.8) ng/mL and mean cfPWV was 1163±303 cm/s. Higher gal-3 concentration was associated with greater central arterial stiffness after adjustment for age, sex, race-center, heart rate, systolic blood pressure, anti-hypertensive medication use, and current smoking status (ß=36.4 cm/s change in cfPWV per log unit change in gal-3; 95% CI: 7.2, 65.5, p=0.015). The association was attenuated after adjusting for additional cardiovascular risk factors (ß=17.3, 95% CI: -14.4, 49.0). Conclusions: In community-dwelling older adults, gal-3 concentration was associated with central arterial stiffness, likely sharing common pathways with traditional cardiovascular risk factors.

Association of Smokeless Tobacco Use With the Use of Other Illicit Drugs in the United States.

BACKGROUND: There has been an increase in the use of smokeless tobacco recently. Whether smokeless tobacco use may predispose individuals to use other addictive substances is unknown. The use of multiple addictive substances may compound an individual's adverse health effects. METHODS: In a cross-sectional analysis, we used the 2016-2017 Behavioral Risk Factor Surveillance System (BRFSS) survey database to identify all individuals who reported the use of smokeless tobacco and extracted data regarding baseline and demographic patterns, as well as information regarding the use of other addictive substances. Weighted multivariable logistic regression models adjusting for age, gender, race/ethnicity, poverty level, education, employment status, and marital status were used to determine the odds ratios (ORs) for use of alcohol, cigarettes, e-cigarettes, and marijuana among smokeless tobacco users. RESULTS: We identified 30,395 (3.38%) individuals in our study population who reported smokeless tobacco use. Compared with non-users, smokeless tobacco users were more likely to be unmarried, male, Caucasian, belonging to the lower socioeconomic strata, and did not have a formal college education (P <0.01). In multivariable analyses, smokeless tobacco use was associated with a higher likelihood of cigarettes use (OR: 1.76 [95% confidence interval {CI}: 1.66-1.86, P <0.01]), e-cigarette use (OR: 1.61 [95% CI: 1.52-1.71, P <0.01]), and heavy alcohol consumption (OR:2.36 [95% CI: 2.17-2.56, P <0.01]) but not marijuana use (OR: 1.11 [95% CI: 0.90-1.38, P = 0.33]). CONCLUSION: In a large, nationally representative sample, smokeless tobacco use was associated with the increased use of cigarettes, e-cigarettes, and alcohol. Simultaneous use of these substances may compound the adverse health effects of smokeless tobacco use. Public health interventions addressing this concerning trend are warranted.

E-cigarette Use and Risk Behaviors among Lesbian, Gay, Bisexual, and Transgender Adults: The Behavioral Risk Factor Surveillance System (BRFSS) Survey.

INTRODUCTION: The prevalence of e-cigarette use among lesbian, gay, bisexual, and transgender (LGBT) individuals and its association with risk behaviors was studied. METHODS: Using data from the Behavioral Risk Factor Surveillance System (BRFSS) survey, self-reported sexual orientation, e-cigarette use, cigarettes, marijuana, smokeless tobacco, and high-risk behavior (using non-prescribed drugs, treatment for sexually transmitted disease, or receiving monetary or drug compensation in exchange for sex in the previous year) were assessed. Multivariable-adjusted logistic regression models were used to study the association between LGBT and risk behaviors. RESULTS: The prevalence of e-cigarette use among LGBT adults was 13%, nearly twice that of heterosexual adults. LGBT adults were more likely [Odds Ratio (95% Confidence Interval)] to report current use of e-cigarettes 1.84 (1.64, 2.06), cigarettes 1.61 (1.49, 1.73), marijuana 2.37 (1.99, 2.82), and high-risk behavior 3.69 (3.40, 4.01) compared to heterosexual adults. Results for smokeless tobacco were not significant. CONCLUSION: There are disparities in e-cigarette and other risk behaviors among LGBT adults, which may increase risk of adverse health effects in this vulnerable population.

Monocyte phenotyping and management of lipoprotein X syndrome.

BACKGROUND: Accumulation of lipoprotein X (LpX) in blood can cause severe hypercholesterolemia and cutaneous xanthomas. Monocytes sensitively sense lipid changes in circulation and contribute to inflammation. However, how monocytes respond to LpX is undefined. OBJECTIVE: We examined the phenotype of monocytes from a patient, who had LpX, severe hypercholesterolemia, and extensive cutaneous xanthomas, and effects of semiselective plasmapheresis therapy (SPPT). METHOD: Fluorescence-activated cell sorting and adhesion assays were used to examine monocyte phenotype and ex vivo oxidized low-density lipoprotein uptake and adhesion in the patient before and after treatment with SPPT. Effects of plasma from the patient on the phenotype and adhesion of monocytes from a healthy participant were determined. RESULTS: SPPT improved hypercholesterolemia and cutaneous xanthomas. Before treatment, the patient had lower frequency of nonclassical monocytes but higher frequency of intermediate monocytes than the control participant. Before treatment, monocytes from the patient with LpX showed more intracellular lipid accumulation, alterations in several cell surface markers and intracellular cytokines, as well as enhanced oxidized low-density lipoprotein uptake and reduced adhesion compared with control. After SPPT, the phenotypes of monocytes from the patient with LpX were similar to control monocytes. Incubation with plasma from the patient before treatment as compared with plasma from the control participant or the patient after treatment increased CD11c expression and adhesion of monocytes from a healthy participant. CONCLUSION: LpX-induced hypercholesterolemia increased lipid accumulation and altered the phenotype of monocytes, which may contribute to cutaneous xanthoma development. Removal of LpX by SPPT reduced lipid accumulation and improved monocyte phenotype, likely contributing to xanthoma resolution.

Highlights of Studies in Cardiovascular Disease Prevention Presented at the 2020 American College of Cardiology Annual Scientific Session.

PURPOSE OF REVIEW: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the American College of Cardiology 2020 Virtual Scientific Session (ACC.20)/World Cardiology Congress (WCC). RECENT FINDINGS: The studies reviewed include clinical trials on the efficacy and safety of alirocumab (Study in Participants with Homozygous Familial Hypercholesterolemia [ODYSSEY HoFH]) and evinacumab in the treatment of homozygous familial hypercholesterolemia (HoFH); Evaluating the Efficacy of E-cigarettes for Smoking Cessation (E3); the use of renal denervation in the treatment of hypertension (SPYRAL HTN-OFF MED PIVOTAL); and the assessment of vericiguat in the treatment of heart failure (A Study of Vericiguat in Participants with Heart Failure with Reduce Ejection Fraction [VICTORIA]). In addition, results from the pooled analysis of phase III trials on inclisiran and secondary analysis examining eicosapentaenoic acid levels and cardiovascular outcomes from the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) were included. Finally, we discuss studies examining the use of polygenic risk score with low density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP) on lifetime cardiovascular risk. The studies presented at the ACC.20/WCC represent notable contributions in the field of CVD prevention.

The Association of Electronic Cigarette Use and the Subjective Domains of Physical and Mental Health: The Behavioral Risk Factor Surveillance System Survey.

Introduction Individuals who use electronic cigarettes (e-cigarettes) may have a poor perception of physical and mental health. We, therefore, studied the association of e-cigarettes with subjectively reported health domains. Methods We utilized cross-sectional data from the 2016 and 2017 Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative U.S. telephone-based survey. All variables were self-reported. E-cigarette use was characterized as never, former, or current. Health domains included overall health, physical health, and mental health, which was assessed as the frequency of emotional support, life satisfaction, and feeling stressed. Weighted multivariable-adjusted logistic regression models were used to examine the association between e-cigarette use and these health domains. Results Our study population consisted of 755,355 (79%) never e-cigarette users, 111,940 (16%) former users, and 28,917 (5%) current users. There was a significant association between e-cigarette use and the less favorable perceived state of overall health, physical health, or mental health. For example, the OR (95% CI) for the association of current e-cigarette use with health domains was as follows: good perception of overall health: 0.78 (0.74,0.83), physical health: 0.69 (0.66,0.73), adequate emotional support: 0.89 (0.79,0.99), feeling satisfied: 0.83 (0.71,0.96), or being free of stress: 0.64 (0.53,0.76). Similar results were obtained in younger individuals (aged 18-34 years). Conclusions E-cigarette use is associated with a less favorable perception of physical and mental health as compared to never use, particularly among younger adults. These results have important implications for clinicians for patient counseling and regulatory agencies to regulate e-cigarette sales.

Temporal Trends in E-Cigarette Use Among U.S. Adults: Behavioral Risk Factor Surveillance System, 2016 to 2018.

BACKGROUND: It is important to study the trends of e-cigarette use among various subgroups to understand which populations may be more susceptible to increased use and, therefore, are at risk for potential long-term health effects. METHODS: We used cross-sectional data from the 2016-2017 Behavioral Risk Factor Surveillance System, a nationally representative U.S. telephone-based survey of adults aged 18 years or older. The 2017 dataset also includes data from participant interviews that had been conducted in the year 2018. Current e-cigarette use was defined as use of e-cigarettes every day or on some days. We analyzed data using survey weights to ensure representativeness of the data to the US population. RESULTS: The study population consisted of 936,319 individuals, of whom 28,917 were current e-cigarette users, and corresponded to 10.8 million U.S. adults. Thirty percent were aged between 18 and 34 years. Forty-nine percent were men; 63% were white, 12% black, and 17% Hispanic. The overall prevalence of current e-cigarette use increased from 4.3% in 2016 to 4.8% in 2018. E-cigarette use significantly increased among middle-aged adults (from 3.9% to 5.2%; P = .004), women (from 3.3% to 4.3%; P <.001), and former smokers (from 5.2% to 7.9%; P = .02), but decreased among current smokers (from 14.5% to 13.8%; P = .02). CONCLUSIONS: In a nationally representative sample, we found important trends in e-cigarette use in a relatively short time frame. A significantly increasing prevalence of e-cigarette use was noted among middle-age adults, women, and former smokers. Our study provides important information about e-cigarette trends that can be used by clinicians when counselling patients and by regulatory agencies to develop public policies.

Highlights from Selected Cardiovascular Disease Prevention Studies Presented at the 2019 European Society of Cardiology Congress.

PURPOSE OF REVIEW: This review intends to highlight selected cardiovascular disease (CVD) prevention studies presented at the 2019 European Society of Cardiology (ESC) Congress. RECENT FINDINGS: Results from the Inclisiran for Subjects with ASCVD or ASCVD-risk Equivalent and Elevated Low-density Lipoprotein Cholesterol (ORION-11) trial validate inclisiran's ability to significantly lower low-density lipoprotein cholesterol (LDL-C) levels in at-risk individuals on a background of maximally tolerated statin therapy. The EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS) trial provide additional support that a PCSK9 inhibitor can be initiated safely and effectively early after an acute coronary syndrome. A sub-study of the Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES) trial provides further support for stratification of secondary prevention patients to help define the magnitude of risk reduction associated with PCSK9 inhibitor therapy. A post hoc analysis from the Aspirin in Reducing Events in the Elderly (ASPREE) trial suggest that any benefits associated with aspirin utilizing a risk-based approach are overwhelmed by increased bleeding risk. In a large retrospective cohort study of patients with diabetes mellitus and obesity, the addition of metabolic (weight loss) surgery to standard care led to greater improvement in CVD outcomes, weight loss, and glycemic control. Results from the Prospective Urban Rural Epidemiology (PURE) study demonstrate that while hypertension and dyslipidemia exert additive lifelong effects on CVD risk, other less established risk factors such as low education, household pollution, and poor diet also have a strong impact on CVD outcomes, especially in middle- and low-income countries. Finally, in the Heart Outcomes Prevention and Evaluation (HOPE) 4 trial, a comprehensive model of care adapted to address multiple barriers of specific communities led to substantial improved blood pressure (BP) control, medication use, and adherence. A number of studies presented at the 2019 ESC Congress reinforced the value of preventative interventions in CVD risk reduction.

Dapagliflozin Attenuates Na+/H+ Exchanger-1 in Cardiofibroblasts via AMPK Activation.

PURPOSE: We assessed whether the SGLT-2 inhibitor dapagliflozin (Dapa) attenuates the upregulation of the cardiac Na+/H+ exchanger (NHE-1) in vitro in mouse cardiofibroblasts stimulated with lipopolysaccharides (LPS) and whether this effect is dependent on adenosine monophosphate kinase (AMPK) activation. METHODS: Mouse cardiofibroblasts were exposed for 16 h to Dapa (0.4 µM), AMPK activator (A769662 (10 µM)), AMPK inhibitor (compound C (CC) (10 µM)), an SGLT-1 and SGLT-2 inhibitor (phlorizin (PZ) (100 µM)), Dapa+CC, or Dapa+PZ, and then stimulated with LPS (10 ng/ml) for 3 h. NHE-1 mRNA levels were assessed by rt-PCR and total AMPK, phosphorylated-AMPK (P-AMPK), NHE-1, and heat shock protein-70 (Hsp70) protein levels in the whole cell lysate by immunoblotting. In addition, NHE-1 protein levels attached to Hsp70 were assessed by immunoprecipitation. RESULTS: Exposure to LPS significantly reduced P-AMPK levels in the cardiofibroblasts. A769662 and Dapa equally increased P-AMPK. The effect was blocked by CC. Phlorizin had no effect on P-AMPK. LPS exposure significantly increased NHE-1 mRNA levels. Both Dapa and A769662 equally attenuated this increase. The effect of Dapa was blocked with CC. Interestingly, none of the compounds significantly affected NHE-1 and Hsp70 protein levels in the whole cell lysate. However, LPS significantly increased the concentration of NHE-1 attached to Hsp70. Both Dapa and A69662 attenuated this association and CC blocked the effect of Dapa. Again, phlorizin had no effect and did not alter the effect of Dapa. CONCLUSIONS: Dapa increases P-AMPK in cardiofibroblasts exposed to LPS. Dapa attenuated the increase in NHE-1 mRNA and the association between NHE-1 and Hsp70. This effect was dependent on AMPK.

Genome sequencing uncovers phenocopies in primary progressive multiple sclerosis.

OBJECTIVE: Primary progressive multiple sclerosis (PPMS) causes accumulation of neurological disability from disease onset without clinical attacks typical of relapsing multiple sclerosis (RMS). However, whether genetic variation influences the disease course remains unclear. We aimed to determine whether mutations causative of neurological disorders that share features with multiple sclerosis (MS) contribute to risk for developing PPMS. METHODS: We examined whole-genome sequencing (WGS) data from 38 PPMS and 81 healthy subjects of European ancestry. We selected pathogenic variants exclusively found in PPMS patients that cause monogenic neurological disorders and performed two rounds of replication genotyping in 746 PPMS, 3,049 RMS, and 1,000 healthy subjects. To refine our findings, we examined the burden of rare, potentially pathogenic mutations in 41 genes that cause hereditary spastic paraplegias (HSPs) in PPMS (n = 314), secondary progressive multiple sclerosis (SPMS; n = 587), RMS (n = 2,248), and healthy subjects (n = 987) genotyped using the MS replication chip. RESULTS: WGS and replication studies identified three pathogenic variants in PPMS patients that cause neurological disorders sharing features with MS: KIF5A p.Ala361Val in spastic paraplegia 10; MLC1 p.Pro92Ser in megalencephalic leukodystrophy with subcortical cysts, and REEP1 c.606 + 43G>T in Spastic Paraplegia 31. Moreover, we detected a significant enrichment of HSP-related mutations in PPMS patients compared to controls (risk ratio [RR] = 1.95; 95% confidence interval [CI], 1.27-2.98; p = 0.002), as well as in SPMS patients compared to controls (RR = 1.57; 95% CI, 1.18-2.10; p = 0.002). Importantly, this enrichment was not detected in RMS. INTERPRETATION: This study provides evidence to support the hypothesis that rare Mendelian genetic variants contribute to the risk for developing progressive forms of MS. Ann Neurol 2018;83:51-63.

Recurrent Biatrial Myxoma in a 41-Year-Old Woman after Left Atrial Myxoma Resection.

Bilateral recurrence of atrial myxoma has been reported only a few times. We describe the case of a 41-year-old woman who had undergone left atrial myxoma resection and presented 9 years later with myxomas in both atria. The patient underwent successful resection of both masses with resolution of symptoms. We discuss the phenomenon of recurrent biatrial myxoma.

Coding variants at hexa-allelic amino acid 13 of HLA-DRB1 explain independent SNP associations with follicular lymphoma risk.

Non-Hodgkin lymphoma represents a diverse group of blood malignancies, of which follicular lymphoma (FL) is a common subtype. Previous genome-wide association studies (GWASs) have identified in the human leukocyte antigen (HLA) class II region multiple independent SNPs that are significantly associated with FL risk. To dissect these signals and determine whether coding variants in HLA genes are responsible for the associations, we conducted imputation, HLA typing, and sequencing in three independent populations for a total of 689 cases and 2,446 controls. We identified a hexa-allelic amino acid polymorphism at position 13 of the HLA-DR beta chain that showed the strongest association with FL within the major histocompatibility complex (MHC) region (multiallelic p = 2.3 × 10⁻¹5). Out of six possible amino acids that occurred at that position within the population, we classified two as high risk (Tyr and Phe), two as low risk (Ser and Arg), and two as moderate risk (His and Gly). There was a 4.2-fold difference in risk (95% confidence interval = 2.9-6.1) between subjects carrying two alleles encoding high-risk amino acids and those carrying two alleles encoding low-risk amino acids (p = 1.01 × 10⁻¹4). This coding variant might explain the complex SNP associations identified by GWASs and suggests a common HLA-DR antigen-driven mechanism for the pathogenesis of FL and rheumatoid arthritis.

[Repair of scar contracture in whole dorsum of hand by expanded full-thickness skin graft].

OBJECTIVE: To investigate the feasibility of repairing secondary wounds after scar excision in patients with scar contracture in whole dorsum of the hands by expanded full-thickness skin grafts. METHODS: Between February 2008 and February 2011, 15 patients (19 hands) with scar contracture in whole dorsum of the hands were treated. There were 12 males (14 hands) and 3 females (5 hands), aged 18-43 years (mean, 28.6 years). The disease duration was 6-22 months (mean, 13.2 months). All cases complicated by different degrees of metacarpophalangeal joint extension deformity and interphalangeal joint flexion deformity. In one-stage operation, soft tissue expanders were implanted at donor sites, and the time of water injection was 4-5 months; in two-stage operation, scar was excised and secondary wound (14 cm x 9 cm-25 cm x 16 cm in size) was repaired with the expanded full-thickness skin grafts. RESULTS: After one-stage operation, the others had good blood supply except 1 case of skin necrosis in the center of expanded skin flap. After two-stage operation, the full-thickness skin grafts survived well in 18 hands; subepidermal effusion occurred in 1 hand, which was cured after changing dressing. The incisions at donor sites healed well in all cases. All patients were followed up 6-18 months (mean, 13.7 months). The grafts were excellent in color, texture, and elasticity, and no hypertrophic scar was observed at the edge and joint of the grafts. The hand function recovered well; the flexion and extension of wrist joint, metacarpophalangeal joint and interphalangeal joint were normal. CONCLUSION: The expanded full-thickness skin graft is a suitable solution to repair effectively scar contracture in whole dorsum of the hands because it has good results in the cosmetic appearance and function recovery of the hands.

[Repairing severe cicatricial contracture deformity in web-space by kite-like incision combined with full-thickness skin grafting].

OBJECTIVE: To investigate the effectiveness of repairing severe cicatricial contracture deformity in the web-space by kite-like incision combined with full-thickness skin grafting. METHODS: Between June 2008 and September 2011, 31 patients (87 web-spaces) with severe cicatricial contracture deformities in the web-spaces were treated. There were 24 males and 7 females, aged 5-43 years (median, 22 years). The causes of injuries were flame burn (26 cases), scald (3 cases), electric arc burn (1 case), and chemical burn (1 case). The degree of burn was deep second degree (14 cases) and third degree (17 cases). The interval time from injury to operation was 10 months to 17 years (median, 2.2 years). The kite-like incision was marked on the scar in the web-space. The rhombic scar between the adjacent metacarpophalangeal joints was excised, and cicatricial contracture was released completely. The secondary wound in the web-space was repaired with full-thickness autogeneic skin grafting. The secondary wound at donor site was directly sutured. RESULTS: All full-thickness skin grafts survived well. The incisions at donor sites healed primarily. Of 31 patients, 29 (82 web-spaces) were followed up 6-18 months (mean, 13 months). The sizes and depths of reconstructed web-spaces were similar to those of normal ones. No secondary cicatricial contracture was observed, and the function of fingers recovered well. CONCLUSION: The short-term effectiveness is satisfactory by kite-like incision combined with full-thickness skin grafting for repairing severe cicatricial contracture deformities in the web-space, while the long-term effectiveness needs further observation.