Polymorphism in KIF6 gene and benefit from statins after acute coronary syndromes: results from the PROVE IT-TIMI 22 study.

OBJECTIVES: We explored whether the benefit of intensive versus moderate statin therapy would be greater in carriers of KIF6 719Arg than in noncarriers. BACKGROUND: The 719Arg variant of Trp719Arg (rs20455), a polymorphism in kinesin-like protein 6, is associated with greater risk of coronary events and greater benefit from pravastatin versus placebo. METHODS: We genotyped 1,778 acute coronary syndrome patients within the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction 22) trial and investigated different intensities of statin therapy in carriers of 719Arg and in noncarriers using Cox proportional hazards models that adjusted for traditional risk factors. RESULTS: Benefit from intensive, compared with moderate, statin therapy was significantly greater in the 59% of the cohort who were carriers (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.45 to 0.77) than in those who were noncarriers (HR 0.94, 95% CI 0.70 to 1.27; p = 0.018 for interaction between 719Arg carrier status and treatment). Absolute risk reduction was 10.0% in carriers versus 0.8% in noncarriers. The benefit of intensive therapy in carriers was significant as early as day 30 of therapy. Carriers and noncarriers did not differ in on-treatment low-density lipoprotein cholesterol, triglyceride, or C-reactive protein (CRP) levels. CONCLUSIONS: Carriers of 719Arg receive significantly greater benefit from intensive statin therapy than do noncarriers, a superior benefit that appears to be due to a mechanism distinct from lipid or CRP lowering. Functional studies of the KIF6 kinesin are warranted, given the consistent association of Trp719Arg with risk of coronary events and statin benefit.     

Short-term, high-dose Atorvastatin pretreatment to prevent contrast-induced nephropathy in patients with acute coronary syndromes undergoing percutaneous coronary intervention (from the ARMYDA-CIN [atorvastatin for reduction of myocardial damage during angioplasty--contrast-induced nephropathy] trial

Contrast-induced nephropathy (CIN) impairs clinical outcome in patients undergoing angiographic procedures. The aim of this study was to investigate whether short-term high-dose atorvastatin load decreases the incidence of CIN after percutaneous coronary intervention (PCI). Statin-naive patients with acute coronary syndrome undergoing PCI (n = 241) randomly received atorvastatin (80 mg 12 hours before intervention with another 40-mg preprocedure dose, n = 120) or placebo (n = 121). All patients had long-term atorvastatin treatment thereafter (40 mg/day). Primary end point was incidence of CIN defined as postintervention increase in serum creatinine ≥0.5 mg/dl or >25% from baseline. Five percent of patients in the atorvastatin arm developed CIN versus 13.2% of those in the placebo arm (p = 0.046). In the atorvastatin group, postprocedure serum creatinine was significantly lower (1.06 ± 0.35 vs 1.12 ± 0.27 mg/dl in placebo, p = 0.01), creatinine clearance was decreased (80.1 ± 32.2 vs 72.0 ± 26.6 ml/min, p = 0.034), and C-reactive protein peak levels after intervention were decreased (8.4 ± 10.5 vs 13.1 ± 20.8 mg/l, p = 0.01). Multivariable analysis showed that atorvastatin pretreatment was independently associated with a decreased risk of CIN (odds ratios 0.34, 95% confidence interval 0.12 to 0.97, p = 0.043). Prevention of CIN with atorvastatin was paralleled by a shorter hospital stay (p = 0.007). In conclusion, short-term pretreatment with high-dose atorvastatin load prevents CIN and shortens hospital stay in patients with acute coronary syndrome undergoing PCI; anti-inflammatory effects may be involved in this renal protection. These results lend further support to early use of high-dose statins as adjuvant pharmacologic therapy before percutaneous coronary revascularization.     

A kinesin family member 6 variant is associated with coronary heart disease in the Women's Health Study.

OBJECTIVES: We asked if carriers of the 719Arg allele of kinesin family member 6 (KIF6) have increased risk of coronary heart disease (CHD) in a cohort of initially healthy Caucasian American women. BACKGROUND: The 719Arg allele of KIF6 (rs20455) has been reported to be associated with increased risk of CHD in a large population-based prospective study, ARIC (Atherosclerosis Risk in Communities), and in the placebo arms of 2 statin trials, CARE (Cholesterol and Recurrent Events) and WOSCOPS (West of Scotland Coronary Prevention Study). However, this KIF6 variant was not specifically investigated in the female subgroup in the ARIC study, and the CARE and WOSCOPS trials included only a small number of female patients. METHODS: Genotypes of the rs20455 single nucleotide polymorphism (SNP) were determined among 25,283 initially healthy Caucasian women, age 45 years and older, participating in the WHS (Women's Health Study) who were prospectively followed over a 12-year period for incident cardiovascular events. The risk associated with the 719Arg allele of KIF6 was estimated using Cox proportional hazards models that adjusted for age and traditional risk factors. RESULTS: During follow-up, 953 women suffered a first-ever CHD event (myocardial infarction, coronary revascularization, or cardiovascular death) or first-ever ischemic stroke. Compared with noncarriers, carriers of the 719Arg allele had an increased risk of CHD (hazard ratio [HR] = 1.24 [95% confidence interval (CI) 1.04 to 1.46, p = 0.013]) and myocardial infarction (HR = 1.34 [95% CI 1.02 to 1.75, p = 0.034]) but not ischemic stroke. CONCLUSIONS: Confirming and extending previous reports, carriers of the 719Arg allele of KIF6 have 34% higher risk of myocardial infarction and 24% higher risk of CHD compared with noncarriers among 25,283 women from the WHS.     

中国北方汉族人2型糖尿病合并冠心病与KIF6基因Trp719Arg多态性的相关性

目的探讨中国北方汉族人群KIF6基因Trp719Arg多态性基因型和等位基因频率分布特点,及与2型糖尿病(DM)合并冠心病(CHD)的关联性。方法采用病例对照研究设计,应用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术分析了对照组(152例)、DM组(97例)、DM+CHD组(76例)KIF6基因Trp719Arg多态性;比较组间基因型和等位基因频率分布差异,研究基因多态性对血糖、血脂水平的影响。结果中国北方汉族人群Trp719Arg多态性TT、TC、CC基因型频率分别为0.281、0.499与0.220。T、C等位基因频率分别为0.531与0.469。KIF6基因Trp719Arg多态性基因型和等位基因频率组间分布差异无统计学意义(均为P>0.05)。KIF6基因Trp719Arg多态性对血糖、血脂水平无显著影响。Logistic回归分析显示,高血压、年龄(≥60岁)、低HDL-C水平(<1.04 mmol/L)是DM+CHD的独立危险因素(OR分别为2.850、12.977和4.006,均为P<0.05),C等位基因与DM+CHD的发生无统计学相关性。结论 KIF6基因Trp719Arg多态性可能不是我国北方汉族人群DM+CHD的独立危险因素。     

KIF6, LPA, TAS2R50, and VAMP8 genetic variation, low density lipoprotein cholesterol lowering response to pravastatin, and heart disease risk reduction in the elderly

Single nucleotide polymorphisms (SNPs) at the KIF6 (kinesin like protein 6, rs20455 or 719Arg), LPA (lipoprotein(a), rs3798220), TAS2R50 (taste receptor type 2, member 50, rs1376251) and VAMP8 (vesicle-associated membrane protein 8, rs1010) have previously been associated with low density lipoprotein cholesterol (LDL-C) lowering response to statins, coronary heart disease (CHD) at baseline, or CHD events on trial. We examined SNPs at the KIF6 (rs20455 or 719Arg), LPA (rs3798220), TAS2R50 (rs1376251) and VAMP8 (rs1010) in 5,411 participants in PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) (mean age 75.3 years), who had been randomized to pravastatin 40 mg/day or placebo and were followed for a mean of 3.2 years. No SNP was related to vascular disease at baseline. Only the KIF6 SNP was related to LDL-C lowering with homozygous Arg 719 subjects being significantly less responsive than other groups (p=0.025, -34.2 vs. -36.1%). With regard to the primary CHD endpoint on trial (fatal or non-fatal myocardial infarction or stroke), we observed a significant relationship for KIF6 719Arg homozygotes (p=0.03, hazards ratio 0.47, 12.8% of the population) in women on pravastatin only, and for TAS2R50 for the AA genotype (p=0.03, hazards ratio 1.76, 8.9% of the population), also only in women on pravastatin. Our data indicate that the assessment of KIF6 rs20455 and TAS2R50 rs1376251 genotypes are not useful for predicting statin induced cardiovascular risk reduction in men, but do predict CHD risk reduction in women in this elderly population. However, these differences are no longer significant after correction for multiple comparisons, and we do not recommend the assessment of any of these SNPs in clinical practice.     

Lack of association between the Trp719Arg polymorphism in kinesin-like protein-6 and cardiovascular risk and efficacy of atorvastatin among subjects with diabetes on dialysis: the 4D study

Aims

We investigated whether KIF6 Trp719Arg genotypes affect cardiovascular outcomes and efficacy of statin therapy in patients with type 2 diabetes mellitus undergoing hemodialysis.

Methods and results

We conducted a post hoc analysis of the 4D-study, a randomized trial including 1255 patients. Patients were randomly assigned to double-blind treatment with either 20 mg of atorvastatin (n = 619) or placebo (n = 636) once daily and followed for 4 years (median). DNA was available for 1232 patients and we assessed KIF6 Trp719Arg genotypes by PCR and subsequent restriction digest. Carriers of the Arg719 allele showed no increased prevalence of cardiovascular disease. The incidence of cardiac death, MI, and stroke did not differ across KIF6 genotypes, irrespective of whether the patients were treated with atorvastatin or not.

Conclusion

In patients with type 2 diabetes mellitus on hemodialysis, KIF6 Trp719Arg genotypes were not associated with adverse cardiovascular outcomes during follow-up or with the efficacy of atorvastatin therapy.     

Statin therapy reduces contrast-induced nephropathy: an analysis of contemporary percutaneous interventions

PURPOSE: We sought to examine whether statin therapy before percutaneous coronary intervention results in reduction in contrast-induced nephropathy (CIN). Intravascular administration of contrast media can have nephrotoxic effects, particularly in patients with baseline renal insufficiency. Along with lowering serum cholesterol, statins have pleiotropic effects in the vasculature. The effect of statin use on CIN is unknown. SUBJECTS AND METHODS: We studied 29409 patients who had both baseline preprocedure and peak postprocedure serum creatinine measured at the time of their percutaneous coronary intervention (PCI). Baseline demographics and creatinine profile before and after the procedure were compared between patients who received preprocedure statins and those who did not. CIN was defined as an increase in serum creatinine of < or =0.5 mg/dL. RESULTS: Baseline serum creatinine was similar between the two groups. When compared with patients who did not receive preprocedure statins, patients on preprocedure statins had a lower incidence of CIN (4.37 vs 5.93, P <0.0001) and nephropathy requiring dialysis (0.32 vs 0.49, P = 0.03). After adjustments for comorbidities, preprocedure statin use was associated with a significant reduction in CIN (odds ration [OR] 0.87, 95% confidence interval [CI] 0.77-0.99, P = 0.03). CONCLUSIONS: Preprocedure statin use is associated with significant reduction in CIN after contemporary PCI. This reinforces the need to initiate statin therapy before percutaneous coronary interventions.     

Critical Appraisal of Guidelines for Antithrombotic Therapy in Atrial Fibrillation Post-Percutaneous Coronary Intervention

Objective:In our present study, our objective was to appraise guidelines on antithrombotic therapy in atrial fibrillation post-percutaneous coronary intervention and to explore the differences in treatment practices for better informed decision-making.Methods:We searched for English language guidelines published between January 2000 and December 2020 at MEDLINE, Embase and websites of guideline organizations. Guidelines with recommendations on antithrombotic regimens for patients with AF undergoing PCI were included. Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was applied to assess guidelines. The reporting of conflicts of interest (COI) was evaluated separately by the RIGHT (Reporting Item for Practice Guidelines in Healthcare) checklist as supplementary items.Results:Sixteen guidelines were included, among which 13 (81.25%) were considered as ‘recommended’ and 1 (6.25%) as ‘unrecommended.’ The average scores of guidelines ranged from 55% to 88% (<60% as low quality, 60–70% as sufficient quality, and >70% as good quality). Among the 6 domains of AGREE II, scope and purpose (84%) and editorial independence(87%) were considered to be the fields in which CPGs performed best, evidenced by the highest mean AGREE II scores. The domains in which the reviewed CPGs received the lowest mean scores were stakeholder involvement (63%) and applicability (58%). The intraclass correlation coefficient scores were excellent in each domain. The overall quality of the selected CPGs was optimal, with the highest score in domain ‘scope and purpose’, and the lowest score in the domain ‘applicability.’ The reporting of COI was satisfactory.Conclusions:For the recommendations on antithrombotic strategies, guidelines with high AGREE II scores still exist discrepancy on the timing and selection. Current guidance documents on the treatment vary in methodological rigor and recommendations are not always consistent.     

Usefulness of statin pretreatment to prevent contrast-induced nephropathy and to improve long-term outcome in patients undergoing percutaneous coronary intervention

Contrast-induced nephropathy (CIN) is an important cause of mortality and morbidity in patients undergoing angiography. This study investigated whether statins decrease incidence of CIN in the setting of percutaneous coronary intervention (PCI) and evaluated the influence of such potential benefit on long-term outcome. Four-hundred thirty-four patients undergoing PCI were prospectively enrolled and followed up to 4 years. Patients were stratified according to preprocedural statin therapy (260 statin treated, 174 statin naive). CIN was defined as a postprocedural increase in serum creatinine of >or=0.5 mg/dl or>25% from baseline. Follow-up assessment included 4-year occurrence of major adverse cardiac events. Statin-treated patients had a significantly lower incidence of CIN (3% vs 27%, p<0.0001; 90% risk decrease) and had better postprocedural creatinine clearance (80+/-20 vs 65+/-16 ml/min, p<0.0001). Benefit of statin before treatment was observed in all subgroups, except in patients with a pre-existing creatinine clearance<40 ml/min. During follow-up, CIN was a predictor of poorer outcome; 4-year survival free of major adverse cardiac events was highest in statin-treated patients without CIN (95%, p相似文献   

Statin therapy and contrast-induced nephropathy after primary angioplasty

A recent study suggested that statin therapy may prevent contrast-induced nephropathy (CIN) following primary angioplasty. Our aim was to assess the effect of statins in this setting in a larger population. We evaluated 589 consecutive patients with acute myocardial infarction who underwent primary angioplasty at our institution. Contrast-induced nephropathy was defined as an increase in serum creatinine by > or =0.5 mg/dL within 72 h following the procedure. Overall, 69 patients (11.9%) developed CIN. The incidence of CIN in the group on statins was 15.9%, as compared with 10.8% in the group not taking statins (p=0.2). Thus, we did not observe a protective effect of statin therapy on CIN development after primary angioplasty.     

Comparison of ACUITY and CRUSADE Scores in Predicting Major Bleeding during Acute Coronary Syndrome

Background

The ACUITY and CRUSADE scores are validated models for prediction of major bleeding events in acute coronary syndrome (ACS). However, the comparative performances of these scores are not known.

Objective

To compare the accuracy of ACUITY and CRUSADE in predicting major bleeding events during ACS.

Methods

This study included 519 patients consecutively admitted for unstable angina, non-ST-elevation or ST-elevation myocardial infarction. The scores were calculated based on admission data. We considered major bleeding events during hospitalization and not related to cardiac surgery, according to the Bleeding Academic Research Consortium (BARC) criteria (type 3 or 5: hemodynamic instability, need for transfusion, drop in hemoglobin ≥ 3 g, and intracranial, intraocular or fatal bleeding).

Results

Major bleeding was observed in 31 patients (23 caused by femoral puncture, 5 digestive, 3 in other sites), an incidence of 6%. While both scores were associated with bleeding, ACUITY demonstrated better C-statistics (0.73, 95% CI = 0.63 - 0.82) as compared with CRUSADE (0.62, 95% CI = 0.53 - 0.71; p = 0.04). The best performance of ACUITY was also reflected by a net reclassification improvement of + 0.19 (p = 0.02) over CRUSADE’s definition of low or high risk. Exploratory analysis suggested that the presence of the variables ‘age’ and ‘type of ACS’ in ACUITY was the main reason for its superiority.

Conclusion

The ACUITY Score is a better predictor of major bleeding when compared with the CRUSADE Score in patients hospitalized for ACS.     

High-dose statin pretreatment for the prevention of contrast-induced nephropathy: a meta-analysis

Background

Contrast-induced nephropathy (CIN) is a rare but serious complication following contrast-based procedures. Statins have been postulated to prevent CIN via various mechanisms. However, the outcomes following statin administration to prevent CIN have been inconsistent.

Methods

A meta-analysis of published randomized clinical trials was performed to determine if short-term administration of high-dose statin is superior to conventional-dose statin or placebo among patients undergoing catheterization and interventional procedures in preventing CIN.

Results

Data were combined across 8 published clinical trials in which 1423 patients were identified. Pooled analyses showed that short-term high-dose statin treatment can decrease the occurrence of CIN (risk ratio 0.51, 95% confidence interval [CI], 0.34-0.77; P = 0.001) and 48-hour serum creatinine level (standardized mean difference [SMD] -0.07 mg/dL; 95% CI, -0.11 to -0.04 mg/dL; P < 0.00001). However, subgroup analysis showed that statin pretreatment cannot decrease the occurrence of CIN in patients with preexisting renal impairment (RR 0.90; 95% CI, 0.49-1.65; P = 0.73). No evidence of publication bias was detected.

Conclusions

This meta-analysis supports the effectiveness of short-term high-dose statin pretreatment for both decreasing the level of serum creatinine and reducing the rate of CIN in patients undergoing diagnostic and interventional procedures requiring contrast media. However, prospective clinical trials will be needed to draw a definitive conclusion in this area.     

Incidence,Predictors and Outcomes of Contrast Induced Nephropathy in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Background:Contrast induced nephropathy (CIN) is considered one of the most common causes of hospital acquired renal failure and severely affects morbidity and mortality. Our objective was to investigate incidence, predictors and outcomes of CIN in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).Methods:The study was conducted on 550 patients with STEMI subjected to PPCI. Patients were classified into two groups according to the occurrence of CIN; group I (Patients without CIN) and group II (Patients with CIN). The two groups were assessed for the clinical outcomes including mortality and major adverse cardiac events (MACE).Results:Incidence of CIN was 10.6%, multivariate regression analysis identified the independent predictors of CIN including; age > 60 years OR 6.083 (CI95% 3.143–11.77, P = 0.001), presence of diabetes mellitus OR 2.491 (CI95% 1.327–4.675, P = 0.005), non-steroidal anti-inflammatory drugs (NSAIDs) use OR 2.708 (CI95% 1.393–5.263, P = 0.003), the volume of contrast agent >200 ml OR 6.543 (CI95% 3.382–12.65, P = 0.001) and cardiogenic shock OR 4.514 (CI95% 1.738–11.72, P = 0.002). Mortality was higher in group II than group I (11.9% vs. 4.4% respectively, P = 0.015). The incidence of MACE were higher in group II than group I (heart failure; 18.6% vs. 7.3%, cardiac arrest; 8.5% vs. 2.8% and cardiogenic shock; 16.9% vs. 6.9% with P. value = 0.003, 0.024, 0.007 respectively).Conclusion:Contrast induced nephropathy was associated with increased morbidity and mortality. The independent predictors of CIN were advanced age, diabetes mellitus, NSAIDs use, the volume of contrast agent >200 ml and cardiogenic shock.     

Statins and Incidence of Contrast-Induced Acute Kidney Injury Following Coronary Angiography - Five Year Experience at a Tertiary Care Center

BackgroundRole of statins in prevention of contrast-induced acute kidney injury (CI-AKI) in patients undergoing coronary angiography remains controversial. We studied the use of statins in decreasing CI-AKI following coronary angiography.MethodsWe reviewed all patients who underwent coronary angiography with or without PCI and had a follow-up creatinine from January 2012 to December 2016 at a single tertiary care center in the United States. CI-AKI was defined as 0.3 mg/dL absolute rise in creatinine. Patients who were on moderate to high-intensity statins or received moderate to high-intensity statins prior to coronary angiography were included in the statin group. Crude and adjusted odds ratios (AOR) were calculated using univariate multiple logistic regression analysis.ResultsOut of 2055 patients (females = 30.7%, mean age 58.0 ± 12.5 years, statin group = 886, non-statin group = 1169), 293 (14.3%) developed CI-AKI. Mean estimated glomerular filtration rate (eGFR) was not significantly different between the statin and the non-statin group (86.5 mL/min/1.73 m² vs 87.1 mL/min/1.73 m², p = 0.65). There was no significant difference in the incidence of CI-AKI between statin and non-statin group (14.4% vs 14.1%, p = 0.83). When adjusted for other risk factors, statin use was not significantly associated with decreased risk of CI-AKI (AOR) = 0.8, [95% confidence interval (CI) = 0.6–1.1, p = 0.19]. Results remained statistically non-significant on subgroup analysis of patients with acute coronary syndrome (ACS) (OR = 0.8, 95% CI = 0.6–1.2, p = 0.27), patients who had percutaneous coronary intervention (PCI) (OR = 1.1, 95% CI = 0.6–1.7, p = 0.81) and patients with eGFR < 60 mL/min/1.73 m² (OR = 0.9, 95% CI = 0.6–1.5, p = 0.9).ConclusionStatin use prior to coronary angiography is not associated with decreased incidence of CI-AKI.     

A Molécula de Lesão Renal-1 está Associada à Nefropatia Induzida por Contraste em Pacientes Idosos com IAMSSST

Background Contrast-induced nephropathy (CIN) is associated with an increased risk of major adverse cardiovascular events (MACE), and the association between CIN and oxidative mechanisms is well documented.Objective This study aimed to evaluate the relationship between serum levels of kidney injury molecule-1 (KIM-1) and CIN in elderly patients with non-ST-segment elevation myocardial infarction (NSTEMI).Methods This study included a total of 758 patients with NSTEMI, who underwent percutaneous coronary intervention (PCI); 15 developed CIN after PCI, and another 104 were the control group, matched for age > 65 years. Baseline to 48-to-72-hour laboratory values and clinical outcomes were recorded. Patients were followed during one year. P values of < 0.05 were considered significant.Results CIN was observed in 12.60% of the patients. Serum KIM-1 was significantly higher in the CIN group than in the non-CIN group (14.02 [9.53 – 19.90] vs. 5.41 [3.41 – 9.03], p < 0.001). The Mehran score was significantly higher in the CIN group than in the non-CIN group (14 [5 – 22] vs. 5 [2 – 7], p = 0.001). MACE were significantly higher in the CIN group than in the non-CIN group (7 [46.70%] vs. 12 [11.50%], p = 0.001). Multivariate logistic regression analysis showed that baseline KIM-1 level (OR = 1.652, 95% CI: 1.20 – 2.27, p = 0.002) and Mehran score (OR = 1.457, 95% CI: 1.01 – 2.08, p = 0.039) were independent predictors of CIN in elderly patients with NSTEMI.Conclusion Baseline serum KIM-1 concentration and Mehran score are independent predictors of CIN in elderly patients with NSTEMI. Additionally, all-cause mortality, cardiovascular death, myocardial reinfarction, stroke, and MACE were significantly higher in the CIN group at one-year follow-up. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)     

Allele and haplotype frequencies for HLA-DQ in Iranian celiac disease patients

AIM: To assess the distribution of human leukocyte antigen (HLA)-DQ2 and -DQ8 in Iranian celiac disease (CD) patients and compare them to healthy Iranian controls.METHODS: To predict the HLA-DQA1 and -DQB1 genes, we used six previously reported HLA-tagging single nucleotide polymorphism to determine HLA genotypes in 59 Iranian patients with ‘biopsy-confirmed’ CD and in 151 healthy Iranian individuals. To test the transferability of the method, 50 cases and controls were also typed using a commercial kit that identifies individual carriers of DQ2, DQ7 and DQ8 alleles.RESULTS: In this pilot study 97% of CD cases (n = 57) and 58% of controls (n = 87) were carriers of HLA-DQ2 and/or HLA-DQ8 heterodimers, either in the homozygous or heterozygous state. The HLA-DQ pattern of these 57 CD patients: heterozygous DQ2.2 (n = 14) and homozygous DQ2.2 (n = 1), heterozygous DQ2.5 (n = 33) and homozygous DQ2.5 (n = 8), heterozygous DQ8 (n = 13) and homozygous DQ8 (n = 2). Two CD patients were negative for both DQ2 and DQ8 (3%).CONCLUSION: The prevalence of DQ8 in our CD population was higher than that reported in other populations (25.4%). As reported in other populations, our results underline the primary importance of HLA-DQ alleles in the Iranian population’s susceptibility to CD.     

Long-term Outcomes after the Discontinuation of Anti-Tumor Necrosis Factor-α Therapy in Patients with Inflammatory Bowel Disease under Clinical Remission: A Korean Association for the Study of Intestinal Disease Multicenter Study

Background/AimsOur study aimed to evaluate the long-term outcomes and risk factors for relapse after anti-tumor necrosis factor (TNF)-α cessation in inflammatory bowel disease (IBD) patients because they are not well established.MethodsA retrospective multicenter cohort study was conducted involving patients with Crohn’s disease (CD) or ulcerative colitis (UC) from 10 referral hospitals in Korea who discontinued first-line anti-TNF therapy after achieving clinical remission.ResultsA total of 109 IBD patients (71 CD and 38 UC) with a median follow-up duration of 56 months were analyzed. The cumulative relapse rates at 1, 3, and 5 years were 11.3%, 46.7%, and 62.5% for CD patients and 28.9%, 45.3%, and 60.9% for UC patients. Multivariable Cox analysis revealed that discontinuation owing to the clinician’s decision was associated with lower risk of relapse (vs patient’s preference hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 to 0.48; p=0.002) and adalimumab use was associated with higher risk of relapse (vs infliximab HR, 4.42; 95% CI, 1.24 to 17.74; p=0.022) in CD patients. Mucosal healing was associated with lower risk of relapse (vs nonmucosal healing HR, 0.12; 95% CI, 0.02 to 0.83; p=0.031) in UC patients. Anti-TNF re-induction was provided to 52 patients, and a response was obtained in 50 patients. However, 25 of them discontinued retreatment owing to a loss of response (n=15), the patient’s preference (n=6), and other factors (n=4).ConclusionsMore than 60% of IBD patients in remission under anti-TNF therapy relapsed within 5 years of treatment cessation. Anti-TNF re-induction was effective. However, half of the patients discontinued anti-TNF therapy, and 50% of these patients discontinued treatment owing to loss of response. (Gut Liver 2021;15-762)     

Intravenous Fluid Therapy Is Associated with a Reduced Incidence of Contrast-Induced Nephropathy but not with a Reduced Long-Term Incidence of Renal Dysfunction After Cardiac Catheterization

BackgroundIntravenous fluid (IVF) administration for the prevention of contrast-induced nephropathy (CIN) is considered standard of care, but the effect of IVF therapy on longer-term outcomes after radiocontrast dye administration is not well known.Methods and resultsWe studied 4367 patients undergoing coronary and peripheral angiography and intervention at a veterans' administration medical center. 2653 patients (61%) received IVF prior to the procedure and 1714 (39%) did not. Of the 4367 subjects 1962 (45%) had repeat creatinine values at 72 h and 3100 (70%) had repeat creatinine values at 3 months. CIN at 72 h occurred in 68 (6.7%) patients in the IVF group and in 87 patients (9.8%) in the group receiving no IVF (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.94–0.99; p = 0.004). At 3 months, renal dysfunction was seen in 224 (11.5%) patients of the IVF group versus 152 (13.1%) of the group receiving no IVF (OR 0.98, CI 0.96–1.01; p = 0.18). In adjusted analyses using a propensity score, IVF therapy was associated with a significant reduction in CIN occurrence at 72 h (OR = 0.97, (95% CI 0.94–0.99, p = 0.01) but was not associated with a change in the incidence of renal dysfunction at 3 months (OR 0.98, 95% CI 0.96–1.01. p = 0.18).ConclusionIn this cohort of US veterans, IVF administration was associated with a decreased incidence of CIN at 72 h but was not associated with a decreased incidence of renal dysfunction at 3 months.     

Analysis of anatomical variations of the lingular artery of the left upper lobe using 3D computed tomography angiography and bronchography

BackgroundThoracic surgeons must be familiar with the anatomy of the pulmonary artery during segmentectomy and segmentectomy. But pulmonary arteries have numerous variations and aberrant branching patterns. The purpose of the present study was to analyze the anatomical variations and frequencies of the lingular artery of the left upper lobe (LUL) using 3D computed tomography angiography and bronchography (3D-CTAB).MethodsWe retrospectively studied 166 patients having undergone lobectomy or segmentectomy from January to December 2020 at Fujian Medical University Cancer Hospital’s Department of Thoracic Surgery. All patients underwent 3D reconstruction using 3D-CTAB before surgery.ResultsThe lingular segment was supplied by 1 artery in 45.18% of cases, 2 arteries in 46.39% of cases, and 3 arteries in 8.43% of cases. The branching patterns of the lingular artery included 119 (71.68%) cases with interlobar origin, 35 (21.08%) cases with interlobar and mediastinal origin, and 13 (7.83%) cases with mediastinal origin. The interlobar lingular artery include superior lingular artery (A4) and inferior lingular artery (A5). The interlobar lingular artery type was A4a, A4b, A5 in 7.23% of cases; A4 and A4b+5 in 3.01% of cases; and A4b and A4a+5 in 4.82% of cases. The mediastinal lingular artery was divided into the following 5 types: ‘A4’, ‘A4b’, ‘A4b+5’, ‘A4b+5a’, and ‘A4+5’. The most common type was A4 (12.05%, 20/166) in 166 patients. The interlobar lingular artery had the following 5 patterns of variation: ‘A4+5’, ‘A4, A5’, ‘A4a, A4b, A5’, ‘A4a, A4b+5’, and ‘A4b, A4a+5’. The single interlobar lingular artery (A4+5) was the most common type in 38.55% of cases. In 24.10% of cases, A5 came from A8 or A8+9. Besides In 8.43% of cases, the origin of A5 was close to A8 or A8+9.ConclusionsWe identified the left various lingular artery branching patterns with 3D-CTAB in patients and defined the frequency of anatomic variations. 3D-CTAB is useful for finding these variations.     

The relationship between pre-procedural elevated arterial lactate and contrast-induced nephropathy following primary percutaneous coronary intervention

BackgroundRisk stratification has been one of the main steps in preventing contrast-induced nephropathy (CIN), which is a common complication after percutaneous coronary intervention (PCI). Elevated arterial lactate is a biomarker indicating severe disease condition and post-intervention complications. The relationship between lactate and CIN has not been established. This study is performed to investigate the relationship between elevated arterial lactate level and contrast-induced nephropathy (CIN).MethodsPatients diagnosed with ST-segment elevated myocardial infarction (STEMI) were prospectively enrolled, with lactate measured within 0.5–1 hours before primary percutaneous coronary intervention (PCI). Patients with cardiopulmonary resuscitation, any forms of severe anaerobic condition, or end-stage renal disease undergoing dialysis were excluded. CIN was defined as an increase in serum creatinine ≥0.5 mg/dL or 25% within 72 hours after PCI. The Mehran Risk Score (MRS) is widely regarded as a classic risk model for CIN and the risk factors of MRS were applied in our multivariate regression analysis.ResultsOf the 227 enrolled patients, 47 (20.7%) developed CIN according to the definition. The mean lactate level was higher in the CIN group than in the non-CIN group (2.68±2.27 vs. 1.74±1.94, P<0.001). The arterial lactate level ≥2.0 mmol/L had 57.5% sensitivity and 75.6% specificity in predicting CIN. The performance of the lactate level in discriminating CIN was similar to that of the MRS (AUC_lac =0.707 vs. AUC_MRS =0.697, P=0.86). After adjusting for other risk factors, lactate ≥2.0 mmol/L still significantly predicted CIN (odds ratio =3.77, 95% CI, 1.77–7.99, P=0.001).ConclusionsAn arterial lactate level of ≥2.0 mmol/L is associated with CIN in STEMI patients after primary PCI.