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Fulltext KIM-1 as a Blood-Based Marker for Early Detection of Kidney Cancer: A Prospective Nested Case-Control Study

Scelo G, Muller DC, Riboli E, Johansson M, Cross AJ, Vineis P, et al.

Clin Cancer Res, 2018 Nov 15;24(22):5594-5601.
PMID: 30037816 DOI: 10.1158/1078-0432.CCR-18-1496

Purpose: Renal cell carcinoma (RCC) has the potential for cure with surgery when diagnosed at an early stage. Kidney injury molecule-1 (KIM-1) has been shown to be elevated in the plasma of RCC patients. We aimed to test whether plasma KIM-1 could represent a means of detecting RCC prior to clinical diagnosis.Experimental Design: KIM-1 concentrations were measured in prediagnostic plasma from 190 RCC cases and 190 controls nested within a population-based prospective cohort study. Cases had entered the cohort up to 5 years before diagnosis, and controls were matched on cases for date of birth, date at blood donation, sex, and country. We applied conditional logistic regression and flexible parametric survival models to evaluate the association between plasma KIM-1 concentrations and RCC risk and survival.Results: The incidence rate ratio (IRR) of RCC for a doubling in KIM-1 concentration was 1.71 [95% confidence interval (CI), 1.44-2.03, P = 4.1 × 10-23], corresponding to an IRR of 63.3 (95% CI, 16.2-246.9) comparing the 80th to the 20th percentiles of the KIM-1 distribution in this sample. Compared with a risk model including known risk factors of RCC (age, sex, country, body mass index, and tobacco smoking status), a risk model additionally including KIM-1 substantially improved discrimination between cases and controls (area under the receiver-operating characteristic curve of 0.8 compared with 0.7). High plasma KIM-1 concentrations were also associated with poorer survival (P = 0.0053).Conclusions: Plasma KIM-1 concentrations could predict RCC incidence up to 5 years prior to diagnosis and were associated with poorer survival. Clin Cancer Res; 24(22); 5594-601. ©2018 AACR.

Matched MeSH terms: Case-Control Studies
Adjuvant chemotherapy in "high risk" patients after Wertheim hysterectomy--10-year survivals

Sivanesaratnam V

Ann Acad Med Singap, 1998 Sep;27(5):622-6.
PMID: 9919328

Although the primary operative mortality following radical hysterectomy for stage IB and early stage IIA cervical carcinoma is less than 1%, survival is poor in those patients with histological evidence of "risk" features--lymph node metastases, lymphatic vascular tumour permeation and clinically undetected parametrial metastases. In the 7-year period 1983 to 1989, 239 patients with stage IB and early IIA disease had radical hysterectomy and pelvic lymphadenectomy. One hundred and eight patients (45.2%) had various poor prognostic histological features and received adjuvant chemotherapy--70 had cisplatin, vinblastine, bleomycin (PVB), 16 had mitomycin C (MMC) and 22 others received mitomycin C + 5-fluorouracil (5-FU). Although not randomised, the risk factors present in each group were identical. These patients have now been followed up for periods ranging from 8 to 14 years. All recurrences, except one, occurred within 23 months of surgery; in the remaining this occurred 8 years later. This suggests that very close long-term follow-up is needed. Recurrences were markedly higher in the group who refused adjuvant chemotherapy (31.6%). The 10-year survival in patients without risk factors was 97.2%. In those patients with risk factors refusing adjuvant therapy it was 73.7%. The adjuvant chemotherapy group had a better survival of 86.1% (P = 0.001). The 10-year survivals in patients with positive nodes were similar--66.7% in the MMC group and 71.4% in the PVB group. The 10-year survival in patients with squamous cell carcinoma was significantly better (90.3%) in the mitomycin C (and MMC + 5-FU) group compared to the PVB group (80.1%) (P = 0.005). The 10-year survival in patients with adenocarcinoma and adenosquamous carcinoma was significantly better (96.3%) in the PVB group compared to those receiving MMC (and MMC + 5-FU) (57.1%) (P = 0.01). It would, thus, appear that the adjuvant chemotherapy of choice for patients with squamous cell carcinoma would be MMC (and MMC + 5-FU) and for those with adenocarcinoma, the PVB regime.

Matched MeSH terms: Case-Control Studies
Vascular Remodeling in Coronary Microvascular Dysfunction

Collet C, Sakai K, Mizukami T, Ohashi H, Bouisset F, Caglioni S, et al.

JACC Cardiovasc Imaging, 2024 Dec;17(12):1463-1476.
PMID: 39269414 DOI: 10.1016/j.jcmg.2024.07.018

BACKGROUND: Approximately one-half of the patients with angina and nonobstructive coronary artery disease (ANOCA) have evidence of coronary microvascular dysfunction (CMD).
OBJECTIVES: This study aims to characterize patients with ANOCA by measuring their minimal microvascular resistance and to examine the pattern of vascular remodeling associated with these measurements.
METHODS: The authors prospectively included patients with ANOCA undergoing continuous thermodilution assessment. Lumen volume and vessel-specific myocardial mass were quantified using coronary computed tomography angiography (CTA). CMD was defined as coronary flow reserve <2.5 and high minimal microvascular resistance as >470 WU.
RESULTS: A total of 153 patients were evaluated; 68 had CMD, and 22 of them showed high microvascular resistance. In patients with CMD, coronary flow reserve was 1.9 ± 0.38 vs 3.2 ± 0.81 in controls (P < 0.001). Lumen volume was significantly correlated with minimal microvascular resistance (r = -0.59 [95% CI: -0.45 to -0.71]; P < 0.001). In patients with CMD and high microvascular resistance, lumen volume was 40% smaller than in controls (512.8 ± 130.3 mm3 vs 853.2 ± 341.2 mm3; P < 0.001). Epicardial lumen volume assessed by coronary CTA was independently associated with minimal microvascular resistance (P < 0.001). The predictive capacity of lumen volume from coronary CTA for detecting high microvascular resistance showed an area under the curve of 0.79 (95% CI: 0.69-0.88).
CONCLUSIONS: Patients with CMD and high minimal microvascular resistance have smaller epicardial vessels than those without CMD. Coronary CTA detected high minimal microvascular resistance with very good diagnostic capacity. Coronary CTA could potentially aid in the diagnostic pathway for patients with ANOCA.

Matched MeSH terms: Case-Control Studies
Fulltext Diagnostic Potential of an IgE-ELISA in Detecting Strongyloidiasis

Ahmad H, Balachandra D, Arifin N, Nolan TJ, Lok JB, Hayat Khan A, et al.

Am J Trop Med Hyg, 2020 12;103(6):2288-2293.
PMID: 32996454 DOI: 10.4269/ajtmh.20-0265

Strongyloides stercoralis infection is prevalent worldwide and can cause lifelong infection in immunocompetent individuals, and potentially death in immunosuppressed patients. The diagnosis is hindered by the low sensitivity of microscopic examination, thus making serology an important complementary test to improve the detection rate. However, there were reports that some Strongyloides-infected individuals were negative with specific IgG and IgG4 assays, and other helminth infections were positive with commercial Strongyloides IgG-ELISAs. Thus, there is a need to develop better serodiagnostic methods for strongyloidiasis. We investigated the diagnostic potential of IgE-ELISAs using Strongyloides larval lysate. Sera from two groups infected with Strongyloides served as the positive reference, that is, 1) positive by commercial IgG-ELISAs and IgG4 rapid test, and stool samples positive by microscopy and/or PCR (group IA; n = 20); and 2) negative by IgG-ELISAs and IgG4 rapid test, but stool samples were PCR positive (group IB sera; n = 11). Sera from another two groups served as negative reference (controls), that is, 1) infected with other parasites (group II; n = 73) and 2) healthy donors (group III; n = 22). Results showed a 100% diagnostic sensitivity in detecting sera from groups IA and IB. The latter group of individuals probably had early infection because their IgG and IgG4 assays were negative. The optical density values of group IB sera were also significantly lower than those of group IA (P < 0.003). The IgE-ELISA was 100% specific when tested against sera from groups II and III. This study highlights the diagnostic potential of IgE-ELISA using larval lysate to detect strongyloidiasis, especially those with probable early infection.

Matched MeSH terms: Case-Control Studies
Fulltext Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the endometrium of women with endometrial cancer and women with polycystic ovary syndrome

Atiomo W, Shafiee MN, Chapman C, Metzler VM, Abouzeid J, Latif A, et al.

Clin Endocrinol (Oxf), 2017 Nov;87(5):557-565.
PMID: 28748640 DOI: 10.1111/cen.13436

OBJECTIVE: Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC).
AIM: To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC.
DESIGN AND METHODS: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study.
RESULTS: We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue (P

Matched MeSH terms: Case-Control Studies
Fulltext Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Stepien M, Jenab M, Freisling H, Becker NP, Czuban M, Tjønneland A, et al.

Carcinogenesis, 2017 Jul 01;38(7):699-707.
PMID: 28575311 DOI: 10.1093/carcin/bgx051

Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression.

Matched MeSH terms: Case-Control Studies
RORA gene rs12912233 and rs880626 polymorphisms and their interaction with SCN1A rs3812718 in the risk of epilepsy: a case-control study in Malaysia

Haerian BS, Sha'ari HM, Tan HJ, Fong CY, Wong SW, Ong LC, et al.

Genomics, 2015 Apr;105(4):229-36.
PMID: 25668517 DOI: 10.1016/j.ygeno.2015.02.001

RAR-related orphan receptors A (RORA) and B (RORB) and voltage-gated sodium channel type 1 (SCN1A) genes play critical roles in the regulation of the circadian clock. Evidence has shown an association of RORA and RORB polymorphisms with susceptibility to autism and depression. Hence, we tested the association of RORA rs12912233, rs16943429, rs880626, rs2290430, and rs12900948; RORB rs1157358, rs7022435, rs3750420, and rs3903529; and SCN1A rs3812718 with epilepsy risk in the Malaysians. DNA was genotyped in 1789 subjects (39% epilepsy patients) by using MassARRAY (Sequenom). Significant association was obtained for rs12912233 in Malaysian Chinese (p=0.003). Interaction between rs12912233-rs880626 and rs3812718 was associated with the epilepsy risk in the subjects overall (p=0.001). Results show that RORA rs12912233 alone might be a possible risk variant for epilepsy in Malaysian Chinese, but that, together with RORA rs880626 and SCN1A rs3812718, this polymorphism may have a synergistic effect in the epilepsy risk in Malaysians.

Matched MeSH terms: Case-Control Studies
Fulltext A potential epigenetic marker mediating serum folate and vitamin B12 levels contributes to the risk of ischemic stroke

Wei LK, Sutherland H, Au A, Camilleri E, Haupt LM, Gan SH, et al.

Biomed Res Int, 2015;2015:167976.
PMID: 25705649 DOI: 10.1155/2015/167976

Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles. We investigated epigenetic dysregulation for the methylenetetrahydrofolate reductase (MTHFR) gene among ischemic stroke patients. Cases and controls were recruited after obtaining signed written informed consents following a screening process against the inclusion/exclusion criteria. Serum vitamin profiles (folate, vitamin B12, and homocysteine) were determined using immunoassays. Methylation profiles for CpGs A and B in the MTHFR gene were determined using a bisulfite-pyrosequencing method. Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating serum folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73-fold. However, both CpGs A and B were not associated with serum homocysteine levels or ischemic stroke severity. CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke.

Matched MeSH terms: Case-Control Studies
High serum level of retinol and α-tocopherol affords protection against oral cancer in a multiethnic population

Athirajan V, Razak IA, Thurairajah N, Ghani WM, Ching HN, Yang YH, et al.

Asian Pac J Cancer Prev, 2014;15(19):8183-9.
PMID: 25339003

BACKGROUND: A comparative cross-sectional study involving oral cancer patients and healthy individuals was designed to investigate associations between retinol, α-tocopherol and β-carotene with the risk of oral cancer.
MATERIALS AND METHODS: This study included a total of 240 matched cases and controls where subjects were selected from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). Retinol, α-tocopherol and β-carotene levels and intake were examined by high-performance liquid chromatography (HPLC) and food frequency questionnaire (FFQ) respectively.
RESULTS: It was found that results from the two methods applied did not correlate, so that further analysis was done using the HPLC method utilising blood serum. Serum levels of retinol and α-tocopherol among cases (0.177±0.081, 1.649±1.670μg/ml) were significantly lower than in controls (0.264±0.137, 3.225±2.054μg/ml) (p<0.005). Although serum level of β-carotene among cases (0.106±0.159 μg/ml) were lower compared to controls (0.134±0.131μg/ml), statistical significance was not observed. Logistic regression analysis showed that high serum level of retinol (OR=0.501, 95% CI=0.254-0.992, p<0.05) and α-tocopherol (OR=0.184, 95% CI=0.091-0.370, p<0.05) was significantly related to lower risk of oral cancer, whereas no relationship was observed between β-carotene and oral cancer risk.
CONCLUSIONS: High serum levels of retinol and α-tocopherol confer protection against oral cancer risk.

Matched MeSH terms: Case-Control Studies
Fulltext Seropositivity and serointensity of Toxoplasma gondii antibodies and DNA among patients with schizophrenia

Omar A, Bakar OC, Adam NF, Osman H, Osman A, Suleiman AH, et al.

Korean J Parasitol, 2015 Feb;53(1):29-34.
PMID: 25748706 DOI: 10.3347/kjp.2015.53.1.29

The aim of this cross sectional case control study was to examine the serofrequency and serointensity of Toxoplasma gondii (Tg) IgG, IgM, and DNA among patients with schizophrenia. A total of 101 patients with schizophrenia and 55 healthy controls from Sungai Buloh Hospital, Selangor, Malaysia and University Malaya Medical Center (UMMC) were included in this study. The diagnosis of schizophrenia was made based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The presence of Tg infection was examined using both indirect (ELISA) and direct (quantitative real-time PCR) detection methods by measuring Tg IgG and IgM and DNA, respectively. The serofrequency of Tg IgG antibodies (51.5%, 52/101) and DNA (32.67%, 33/101) among patients with schizophrenia was significantly higher than IgG (18.2%, 10/55) and DNA (3.64%, 2/55) of the controls (IgG, P=0.000, OD=4.8, CI=2.2-10.5; DNA, P=0.000, OD=12.9, CI=2.17-10.51). However, the Tg IgM antibody between patients with schizophrenia and controls was not significant (P>0.005). There was no significant difference (P>0.005) in both serointensity of Tg IgG and DNA between patients with schizophrenia and controls. These findings have further demonstrated the strong association between the active Tg infection and schizophrenia.

Matched MeSH terms: Case-Control Studies
Association of Cholesteryl Ester Transfer Protein and Endothelial Nitric Oxide Synthase Gene Polymorphisms With Coronary Artery Disease in the Multi-Ethnic Malaysian Population

Chu WC, Aziz AF, Nordin AJ, Cheah YK

Clin Appl Thromb Hemost, 2016 Sep;22(6):581-8.
PMID: 25667236 DOI: 10.1177/1076029615571628

Genetic variants of cholesteryl ester transfer protein (CETP) and endothelial nitric oxide synthase (eNOS) influence high-density lipoprotein cholesterol (HDL-C) metabolism and nitric oxide (NO) synthesis, respectively, and might increase the risk of coronary artery disease (CAD). This study is to investigate the relationship between genetic polymorphisms and the risk of CAD and to evaluate their potential interactions. A total of 237 patients with CAD and 101 controls were genotyped. The association of the polymorphism with the risk of CAD varied among the ethnic groups. Moreover, the concomitant presence of both CETP B1 and eNOS 4a alleles significantly increased the risk of CAD in the Malay group (OR = 33.8, P < .001) and the Indian group (OR = 10.9, P = .031) but not in the Chinese group. This study has identified a novel ethnic-specific gene-gene interaction and suggested that the combination of CETP B1 allele and eNOS 4a allele significantly increases the risk of CAD in Malays and Indians.

Matched MeSH terms: Case-Control Studies
Autophagy in Helicobacter pylori Infection and Related Gastric Cancer

Castaño-Rodríguez N, Kaakoush NO, Goh KL, Fock KM, Mitchell HM

Helicobacter, 2015 Oct;20(5):353-69.
PMID: 25664588 DOI: 10.1111/hel.12211

Autophagy, a degradation pathway in which cytoplasmic content is engulfed and degraded by lysosomal hydrolases, plays a pivotal role in infection and inflammation. Given that defects in autophagy lead to increased susceptibility to infection, we investigated the role of autophagy in Helicobacter pylori-related gastric cancer (GC).

Matched MeSH terms: Case-Control Studies
The relation of preeclampsia and serum level of 25-hydroxyvitamin D in mothers and their neonates: a case control study in Iran

Mohaghegh Z, Abedi P, Dilgouni T, Namvar F, Ruzafza S

Horm. Metab. Res., 2015 Apr;47(4):284-8.
PMID: 25611206 DOI: 10.1055/s-0034-1395607

The predisposing factors of preeclampsia may endanger the mother's heath as well as her neonate. One hypothesis related to preeclampsia is vitamin D deficiency or insufficiency. This study was conducted to evaluate the relationship between preeclampsia and the serum level of 25-hydroxyvitamin D (25-OH-D) in mothers and their neonates. In this case-control study, we recruited 41 preeclamptic and 50 healthy women from the Imam Khomeini Hospital in Ahvaz, Iran. Venous blood (2 ml) from mothers (in time of labor) and 2 ml of blood from the umbilical cord were taken, centrifuged, stored at -30°C and sent to a laboratory for analysis of 25-OH-D by ELISA. Vitamin D levels<20 ng/ml were regarded as deficiency, levels between 21-29 ng/ml were regarded as insufficiency, and if levels were higher than 30 ng/ml, these were considered normal. Independent t-test, chi-square, Spearman correlation coefficient and logistic regression were used to analyze data. Mean levels of 25-OH-D were significantly lower in preeclamptic women (15.2±13.6 vs. 23.3±15.3 ng/ml, p=0.001) and in their neonates (15.2±13.1 vs. 21.6±12.6 ng/ml, p=0.01) compared to normal pregnant women and their neonates. There was a significant relationship between the levels of vitamin D in preeclamptic women with levels of this vitamin in their neonates (r=0.901, p=0.0001). 25-OH-D deficiency that exist in preeclamptic mothers, may be a health risk for their infants, therefore, early use of vitamin D supplement with higher dose than 400 IU in Iranian women is recommended.

Matched MeSH terms: Case-Control Studies
Hepatitis C virus prevalence and genotyping among hepatocellular carcinoma patients in Baghdad

Al-Kubaisy WA, Obaid KJ, Noor NA, Ibrahim NS, Al-Azawi AA

Asian Pac J Cancer Prev, 2014;15(18):7725-30.
PMID: 25292053

Hepatocellular carcinoma (HCC) is the third most common cause for cancer death in the world, now being especially linked to chronic hepatitis C virus (HCV) infection. This case-control study consisting of 65 HCC patients and 82 patients with other malignant tumours as controls was conducted to determine the association of HCV markers with HCC. Serum of each participant was obtained for detection of HCV Ab and RNA by DNA enzyme immunoassay (DEIA). Twenty six per cent (26.0%) of HCC patients had positive anti-HCV which was significantly greater than the control group (p=0.001). HCC patients significantly have a risk of exposure to HCV infection almost 3 times than the control group (OR=2.87, 95% C.I=1.1-7). Anti-HCV seropositive rate was significantly (p=0.03) higher among old age HCC patients and increases with age. Males with HCC significantly showed to have more than 9 times risk of exposure to HCV infection (OR=9.375, 95 % CI=1.299-67.647) than females. HCV-RNA seropositive rate was (70.8%) significantly higher among HCC patients compared to (22.2%) the control group (p=0.019). The most prevalent genotype (as a single or mixed pattern of infection) was HCV- 1b. This study detected a significantly higher HCV seropositive rate of antibodies and RNA in HCC patients.

Matched MeSH terms: Case-Control Studies
Fulltext The involvement of miR-23a/APAF1 regulation axis in colorectal cancer

Yong FL, Wang CW, Roslani AC, Law CW

Int J Mol Sci, 2014 Jul 02;15(7):11713-29.
PMID: 24992592 DOI: 10.3390/ijms150711713

Recent advances in microRNAome have made microRNAs (miRNAs) a compelling novel class of biomarker in cancer biology. In the present study, the role of miR-23a in the carcinogenesis of colorectal cancer (CRC) was investigated. Cell viability, apoptosis, and caspase 3/7 activation analyses were conducted to determine the potentiality of apoptosis resistance function of miR-23a in CRC. Luciferase assay was performed to verify a putative target site of miR-23a in the 3'-UTR of apoptosis protease activating factor 1 (APAF1) mRNA. The expression levels of miR-23a and APAF1 in CRC cell lines (SW480 and SW620) and clinical samples were assessed using reverse transcription-quantitative real-time PCR (RT-qPCR) and Western blot. We found that the inhibition of miR-23a in SW480 and SW620 cell lines resulted in significant reduction of cell viability and promotion of cell apoptosis. Moreover, miR-23a up-regulation was coupled with APAF1 down-regulation in CRC tissue samples. Taken together, miR-23a was identified to regulate apoptosis in CRC. Our study highlights the potential application of miR-23a/APAF1 regulation axis in miRNA-based therapy and prognostication.

Matched MeSH terms: Case-Control Studies
Fulltext Methotrexate-associated nonalcoholic fatty liver disease with transaminitis in rheumatoid arthritis

Sakthiswary R, Chan GY, Koh ET, Leong KP, Thong BY

ScientificWorldJournal, 2014;2014:823763.
PMID: 24971392 DOI: 10.1155/2014/823763

BACKGROUND: The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore.
METHODS: Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis.
RESULTS: Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512).
CONCLUSION: The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.

Study site: Tan Tock Seng Hospital, Singapore

Matched MeSH terms: Case-Control Studies
Genetic variants associated with phenytoin-related severe cutaneous adverse reactions

Chung WH, Chang WC, Lee YS, Wu YY, Yang CH, Ho HC, et al.

JAMA, 2014 Aug 6;312(5):525-34.
PMID: 25096692 DOI: 10.1001/jama.2014.7859

The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown.

Matched MeSH terms: Case-Control Studies
Early effect of hydroxychloroquine therapy: relationship between cumulative dose and retinal thickness

Agarwal P, Wong YH, Das Gupta E, Agarwal R, Livingstone BI, Ramamurthy S, et al.

Cutan Ocul Toxicol, 2015;34(3):179-84.
PMID: 25068998 DOI: 10.3109/15569527.2014.938751

BACKGROUND: Hydroxychloroquine (HCQ) is widely used for long-term treatment of autoimmune diseases such as rheumatoid arthritis. However, its long-term use is known to be associated with visual changes due to retinal damage. Retinal damage associated with long-term HCQ therapy is preventable if the drug is discontinued early when the patients are still asymptomatic. In view of contrasting reports from previous studies, we investigated the association of prolonged HCQ therapy with retinal thickness in macular area.
METHODS: This study included 48 patients on long-term HCQ therapy and 38 healthy controls. All subjects underwent examination for corrected visual acuity, fundus photography, visual fields and SD-OCT for retinal thickness.
RESULTS: Visual acuity, visual fields, fundus photography and SD-OCT did not reveal changes consistent with diagnosis of established HCQ retinopathy in any of the subjects from HCQ group. Retinal thickness in central, parafoveal and perifoveal areas did not show significant differences between HCQ and control groups. However, we observed negative correlation between cumulative dose and retinal thickness in the parafoveal (p = 0.003) and perifoveal areas (p = 0.019) but not in the central area.
CONCLUSIONS: Correlation of cumulative dose with retinal thickness in parafoveal and perifoveal areas and not the central area is in accordance with the late appearance of HCQ-induced bull's eye retinopathy. Hence screening of asymptomatic patients using OCT seems to be of great importance for early detection of retinal changes.
KEYWORDS: Cumulative dose; OCT; hydroxychloroquine; retinal thickness

Matched MeSH terms: Case-Control Studies
Fulltext Does cultural practice affects neonatal survival- a case control study among low birth weight babies in Aceh Province, Indonesia

Sutan R, Berkat S

BMC Pregnancy Childbirth, 2014;14:342.
PMID: 25269390 DOI: 10.1186/1471-2393-14-342

BACKGROUND: Cultural practice have often overlooked when providing maternal and child health care services. Low birth weight is the second cause of neonatal mortality in the world but it is a major factor in a developing country such as Indonesia. The purpose of this study is to predict the neonatal mortality among low birth weight babies in Aceh Province Indonesia.
METHODS: Unmatched case control study was conducted using data from year 2010 to 2012 in 8 selected districts of Aceh Province Indonesia. A total of 500 samples were obtained. There were 250 of the samples died in neonatal period (case group) and 250 who were alive (control group). There were 26 variables studied and were grouped into 4 factors: neonatal factor, maternal factor, maternal and child health services and neonatal care practices. The data was analysed using bivariate logistic regression and multivariate logistic regression.
RESULTS: There were 13 out of 26 variables found as determinant factors of neonatal mortality among low birth weight babies in Aceh Province. The predictors found in this study were: boy (aOR1.80, 95% CI: 1.09-2.96), moderate low birth weight (aOR17.84, 95% CI: 6.20-51.35), preterm (aOR1.84, 95% CI: 1.07- 3.17), presence of maternal illnesses (aOR1.87, 95% CI: 1.06-3.30), too short or too long birth interval (aOR1.80, 95% CI: 1.20-2.91), inappropriate antenatal care (aOR2.29, 95% CI: 1.34-3.91), inappropriate neonatal visit (aOR7.04, 95% CI: 3.67-13.49), not practicing kangaroo mother care (aOR15.32, 95% CI: 2.85-82.56), not using warm bottle padding (aOR20.70, 95% CI: 6.32-67.80), not practicing 'didaring' (aOR4.33, 95% CI: 1.83-10.19), late initiation of breastfeeding (aOR2.03, 95% CI: 1.09-3.80), discard colostrums (aOR3.53, 95% CI: 1.93-6.43) and not practicing exclusive breastfeeding (aOR5.58, 95% CI: 2.89-10.77).
CONCLUSIONS: Cultural practices are strongly seen among Acehnese. Inappropriate antenatal care and neonatal care, late initiation of breastfeeding, discarding colostrums and not practicing exclusive breastfeeding were related to cultural practices. Improving knowledge heat preservation to prevent hypothermia using Kangaroo mother care, warm bottle padding and 'didaring' were proven methods to reduce neonatal mortality. Strengthening of health services in screening for high risk cases and anticipate intervention tailored to cultural practices are important to decrease neonatal mortality among low birth weight.

Matched MeSH terms: Case-Control Studies
Aberrant proteins featured in the saliva of habitual betel quid chewers: an indication of early oral premalignancy?

Jessie K, Jayapalan JJ, Rahim ZH, Hashim OH

Electrophoresis, 2014 Dec;35(24):3504-11.
PMID: 25223738 DOI: 10.1002/elps.201400252

Prolonged chewing of betel quid is known to cause oral diseases, including cancer. The present study was performed to screen for aberrant proteins in the saliva of habitual betel quid chewers compared to nonchewers. Saliva of female subjects (n = 10) who had been chewing betel quid for more than 20 years and nonbetel quid chewers (n = 10) of the same gender and range of age was analyzed by gel-based proteomics. Increased structural microheterogeneity of saliva haptoglobin beta chains indicated by shifts of focused spots similar to that earlier reported in patients with oral squamous cell carcinoma, and their relatively higher abundance compared to nonbetel quid chewers, were detected in saliva protein profiles of all chewers. In addition, the majority of the betel quid chewers also showed significant higher abundance of hemopexin, alpha-1B glycoprotein, alpha1-antitrypsin, complement C3, and transthyretin. These proteins had previously been associated with several different cancers. Our data demonstrated different forms of protein aberration in the saliva of betel quid chewers, which may be indicative of early oral precancerous conditions.

Matched MeSH terms: Case-Control Studies

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