Nevin Manimala

Nucleic Acids Res. 2021 Oct 20:gkab957. doi: 10.1093/nar/gkab957. Online ahead of print.

ABSTRACT

The development of transcriptome-wide association studies (TWAS) has enabled researchers to better identify and interpret causal genes in many diseases. However, there are currently no resources providing a comprehensive listing of gene-disease associations discovered by TWAS from published GWAS summary statistics. TWAS analyses are also difficult to conduct due to the complexity of TWAS software pipelines. To address these issues, we introduce a new resource called webTWAS, which integrates a database of the most comprehensive disease GWAS datasets currently available with credible sets of potential causal genes identified by multiple TWAS software packages. Specifically, a total of 235 064 gene-diseases associations for a wide range of human diseases are prioritized from 1298 high-quality downloadable European GWAS summary statistics. Associations are calculated with seven different statistical models based on three popular and representative TWAS software packages. Users can explore associations at the gene or disease level, and easily search for related studies or diseases using the MeSH disease tree. Since the effects of diseases are highly tissue-specific, webTWAS applies tissue-specific enrichment analysis to identify significant tissues. A user-friendly web server is also available to run custom TWAS analyses on user-provided GWAS summary statistics data. webTWAS is freely available at http://www.webtwas.net.

PMID:34669946 | DOI:10.1093/nar/gkab957

Int J Epidemiol. 2021 Oct 20:dyab203. doi: 10.1093/ije/dyab203. Online ahead of print.

ABSTRACT

BACKGROUND: This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization.

METHODS: A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were identified as exposures from PubMed. We defined the CKD by clinical diagnosis or by estimated glomerular filtration rate of <60 ml/min/1.73 m2. Ultimately, 51 672 CKD cases and 958 102 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13 093 CKD cases and 238 118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank/ToMMo were included.

RESULTS: Eight risk factors showed reliable evidence of causal effects on CKD in Europeans, including genetically predicted body mass index (BMI), hypertension, systolic blood pressure, high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein(a), type 2 diabetes (T2D) and nephrolithiasis. In East Asians, BMI, T2D and nephrolithiasis showed evidence of causality on CKD. In two independent replication analyses, we observed that increased hypertension risk showed reliable evidence of a causal effect on increasing CKD risk in Europeans but in contrast showed a null effect in East Asians. Although liability to T2D showed consistent effects on CKD, the effects of glycaemic phenotypes on CKD were weak. Non-linear Mendelian randomization indicated a threshold relationship between genetically predicted BMI and CKD, with increased risk at BMI of >25 kg/m2.

CONCLUSIONS: Eight cardiometabolic risk factors showed causal effects on CKD in Europeans and three of them showed causality in East Asians, providing insights into the design of future interventions to reduce the burden of CKD.

PMID:34669934 | DOI:10.1093/ije/dyab203

Inflamm Bowel Dis. 2021 Oct 20;27(11):1731-1739. doi: 10.1093/ibd/izaa344.

ABSTRACT

BACKGROUND: Dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet’s syndrome, and aphthous stomatitis can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs). Rarely, they may precede IBD. Other common conditions such as psoriasis have also been associated with IBD. This study examined the risk of a subsequent IBD diagnosis in patients presenting with a D-EIM.

METHODS: A retrospective cohort study compared patients with D-EIMs and age-/sex-matched patients without D-EIMs. Hazard ratios (HRs) were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, loperamide use, anemia, and lower gastrointestinal symptoms. Logistic regression was used to produce a prediction model for the diagnosis of IBD within 3 years of EN diagnosis.

RESULTS: We matched 7447 patients with D-EIMs (74% female; median age 38 years (interquartile ratio [IQR], 24-65 years) to 29,297 patients without D-EIMs. We observed 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs. Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs and 1594 days (IQR, 693-2841 days) in those without D-EIMs. The adjusted HR for a later diagnosis of IBD was 6.16 (95% confidence interval [CI], 4.53-8.37; P < 0.001), for ulcerative colitis the HR was 3.30 (95% CI, 1.98-5.53; P < 0.001), and for Crohn’s disease the HR was 8.54 (95% CI, 5.74-12.70; P < 0.001). Patients with psoriasis had a 34% increased risk of a subsequent IBD diagnosis compared with the matched control patients (HR, 1.34; 95% CI, 1.20-1.51; P < 0.001). We included 4043 patients with an incident EN diagnosis in the prediction model cohort, with 87 patients (2.2%) diagnosed with IBD within 3 years. The model had a bias-corrected c-statistic of 0.82 (95% CI, 0.78-0.86).

CONCLUSIONS: Patients with D-EIMs have a 6-fold increased risk of a later diagnosis of IBD. Younger age, smoking, low body mass index, anemia, and lower gastrointestinal symptoms were associated with an increased risk of diagnosis of IBD within 3 years in patients with EN.

PMID:34669933 | DOI:10.1093/ibd/izaa344

Arch Pathol Lab Med. 2021 Oct 20. doi: 10.5858/arpa.2020-0712-OA. Online ahead of print.

ABSTRACT

CONTEXT.—: The use of whole slide images (WSIs) in diagnostic pathology presents special challenges for the cytopathologist. Informative areas on a direct smear from a thyroid fine-needle aspiration biopsy (FNAB) smear may be spread across a large area comprising blood and dead space. Manually navigating through these areas makes screening and evaluation of FNA smears on a digital platform time-consuming and laborious. We designed a machine learning algorithm that can identify regions of interest (ROIs) on thyroid fine-needle aspiration biopsy WSIs.

OBJECTIVE.—: To evaluate the ability of the machine learning algorithm and screening software to identify and screen for a subset of informative ROIs on a thyroid FNA WSI that can be used for final diagnosis.

DESIGN.—: A representative slide from each of 109 consecutive thyroid fine-needle aspiration biopsies was scanned. A cytopathologist reviewed each WSI and recorded a diagnosis. The machine learning algorithm screened and selected a subset of 100 ROIs from each WSI to present as an image gallery to the same cytopathologist after a washout period of 117 days.

RESULTS.—: Concordance between the diagnoses using WSIs and those using the machine learning algorithm-generated ROI image gallery was evaluated using pairwise weighted κ statistics. Almost perfect concordance was seen between the 2 methods with a κ score of 0.924.

CONCLUSIONS.—: Our results show the potential of the screening software as an effective screening tool with the potential to reduce cytopathologist workloads.

PMID:34669924 | DOI:10.5858/arpa.2020-0712-OA

Rev Bras Enferm. 2021 Oct 18;75(2):e20210019. doi: 10.1590/0034-7167-2021-0019. eCollection 2021.

ABSTRACT

OBJECTIVE: To verify the association between adherence to antiretroviral treatment by adults with HIV/AIDS and sociodemographic factors, social and clinical support.

METHODS: Cross-sectional study, with a quantitative approach. Participation of 230 patients. Questionnaires of sociodemographic characterization, social and clinical support, and assessment of adherence to antiretroviral treatment were used. Descriptive and inferential statistics were performed.

RESULTS: Adherence was classified as good/adequate. An association with sex, income, employment, and level of education was noted. In social support: having access to health services; communication with health professionals; health education; having support to allow venting/talking about issues; information on HIV/AIDS; and company for leisure. In the clinical profile: non-interruption of the drug treatment due to absence from the service or due to changes in the medical prescription.

CONCLUSION: Adherence was classified as good/adequate and especially associated with social support factors, which should be enhanced in clinical practice.

PMID:34669905 | DOI:10.1590/0034-7167-2021-0019

Arq Bras Cir Dig. 2021 Oct 15;34(2):e1602. doi: 10.1590/0102-672020210002e1602. eCollection 2021.

ABSTRACT

BACKGROUND: Morbid obesity surgery and related complications have increased with time.

AIM: To evaluate the relationship between perioperative complications before discharge and preoperative body mass index and obesity surgery mortality score in laparoscopic sleeve gastrectomy.

METHOD: 1617 patients who met the inclusion criteria were evaluated retrospectively. The patients were examined in terms of demographic data, presence of comorbidities, whether there were complications or not, type of complications and obesity surgery mortality score.

RESULTS: Complications were seen in 40 patients (2.5%) and mortality wasn’t seen in the early postoperative period before discharge. The mean age of patients with complications was 36.3±10.02 years (19-57) and without complications 34.12±9.54 (15-64) years. The preoperative mean BMI values of patients with and without complications were 45.05±3.93 (40-57) kg/m2 and 44.8±3.49 (35-67) kg/m2 respectively. According to BMI groups 40-45 kg/m2, 45-50 kg/m2 and 50 and over, there was not any statistical significance seen in three groups in terms of complication positivity and major-minor complication rates. There was not any statistical significance seen between the patients with and without major-minor complications and obesity surgery mortality score.

CONCLUSION: There was not any relation between perioperative laparoscopic sleeve gastrectomy complication rates before discharge and BMI and obesity surgery mortality scores.

PMID:34669891 | DOI:10.1590/0102-672020210002e1602

Clinics (Sao Paulo). 2021 Oct 18;76:e3002. doi: 10.6061/clinics/2021/e3002. eCollection 2021.

ABSTRACT

OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is an important clinical problem that can be aggravated by diabetes mellitus, a major risk factor. However, heme oxygenase-1 (HO-1), a promising therapeutic target, can exert antioxidant effects against CI-AKI. Thus, we investigated the role of HO-1 in CI-AKI in the presence of diabetes mellitus.

METHODS: Twenty-eight male Wistar rats weighing 250-300g were subjected to left uninephrectomy, and concomitantly, diabetes induced by streptozotocin (65 mg/kg). After 12 weeks, iodinated contrast (meglumine ioxithalamate, 6 mL/kg) and hemin (HO-1 inducer-10 mg/k) were administered 60 min before iodinated contrast treatment. The rats were randomly divided into four groups: control, diabetes mellitus (DM), DM iodinated contrast (DMIC), and DMIC hemin (DMICH). Kidney function, albuminuria, oxidative profile, and histology were assessed. All experimental data were subjected to statistical analyses.

RESULTS: CI-AKI in preclinical diabetic models decreased creatinine clearance and increased urinary neutrophil gelatinase-associated lipocalin (NGAL) levels and the degree of albuminuria. Additionally, the levels of oxidative and nitrosative stress metabolites (urinary peroxides, thiobarbituric acid-reactive substances, and NO) were elevated, while thiol levels in kidney tissue were reduced. Kidney histology showed tubular cell vacuolization and edema. HO-1 inducer treatment improved kidney function and reduced urinary the NGAL levels. The oxidative profile showed an increase in the endogenous thiol-based antioxidant levels. Additionally, the tubular injury score was reduced following HO-1 treatment.

CONCLUSIONS: Our findings highlight the renoprotective effects of HO-1 in CI-AKI and preclinical diabetic models. Therefore, HO-1 ameliorates kidney dysfunction, reduces oxidative stress, and prevents cell necrosis.

PMID:34669875 | DOI:10.6061/clinics/2021/e3002

Clinics (Sao Paulo). 2021 Oct 18;76:e2942. doi: 10.6061/clinics/2021/e2942. eCollection 2021.

ABSTRACT

OBJECTIVES: This study assessed the protective effect of calcium dobesilate against contrast-induced nephropathy (CIN) after coronary angiography (CAG) or percutaneous coronary intervention (PCI) in patients with diabetes and chronic kidney disease (CKD).

METHODS: A total of 130 patients with diabetes and CKD estimated glomerular filtration rate: 30-90 mL/min/1.73m2 were enrolled and included in the analysis. They were divided into experimental (n=65) and control groups (n=65). Patients in the experimental group were administered oral calcium dobesilate (500 mg) three times daily for 2 days before and 3 days after the procedure. The serum creatinine (SCr), cystatin C (Cys C), and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured before and after the procedure.

RESULTS: The mean SCr level at 24h after the procedure was found to be significantly lower in the experimental group than in the control group (79.1±19.6 μmol/L vs. 87.0±19.3 μmol/L, p=0.023). However, the Cys C and NGAL levels were not significantly different between the two groups at all measurement time points (all p>0.05). The incidence of CIN defined by the SCr level was significantly lower in the experimental group than in the control group (3 [4.6%] vs. 13 [20.0%], p=0.017). However, the incidence of CIN defined by the Cys C level was not statistically different between the two groups (7 [10.8%] vs. 7 [10.8%], p=1.000).

CONCLUSIONS: This study revealed that calcium dobesilate has no preventive effect against CIN in patients with diabetes and CKD.

PMID:34669873 | DOI:10.6061/clinics/2021/e2942

Rev Assoc Med Bras (1992). 2021 Aug;67(8):1155-1160. doi: 10.1590/1806-9282.20210560.

ABSTRACT

OBJECTIVE: Acute calculous cholecystitis (AC) is a frequently encountered emergency surgery disease and its standard treatment is cholecystectomy. In patients with high risk in surgery, antibiotic treatment (AT) is important. In routine clinical practices, antibiotics are frequently used either as single or in combination in the treatment of AC. This study examined whether or not combined antibiotic treatment (CAT) had superiority over single antibiotic treatment (SAT) in AC.

METHODS: Patients with cholecystitis who received treatment in the period of 2016-2019 were retrospectively examined. The treatment procedures applied, patient findings, and laboratory data were analyzed using relevant statistical software. The patients were categorized into groups based on the treatment approaches applied, and the effects of SAT and CAT on infection parameters were analyzed.

RESULTS: In all, 184 patients received treatment for AC, with a mean age of 57.7, and the female-to-male ratio was 77:107. Of these, 139 patients received SAT and 45 received CAT. No significant difference was found in terms of effectiveness between the SAT and CAT in the patients who received early cholecystectomy treatment and those who received medical treatment with noninvasive intervention.

CONCLUSIONS: In patients with AC, antibiotics are commonly used either as single or in combination for prophylaxis and therapeutic purposes. As no significant difference was observed between single and combined use in terms of treatment effectiveness and hospitalization duration, CAT is not recommended due to its possibility of allergic side effects, toxicity, and cost-increasing effects.

PMID:34669862 | DOI:10.1590/1806-9282.20210560

Rev Assoc Med Bras (1992). 2021 Aug;67(8):1113-1117. doi: 10.1590/1806-9282.20210451.

ABSTRACT

OBJECTIVE: Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Previous studies have indicated the involvement of vitamin D receptor (VDR) and related long noncoding RNAs (lncRNAs) signaling in the pathophysiology of several cancers. However, their contribution to ALL remains to be elucidated.

METHODS: In this case-control study, 30 patients with newly diagnosed ALL and 30 age- and sex-matched healthy children were selected. Then, the level of 25(OH) vitamin D and the expression of VDR and four VDR-related lncRNAs were assessed.

RESULTS: No significant difference in serum 25(OH) vitamin D was observed between patients with ALL (20.42±6.5 ng/mL) and healthy subjects (25.45±11 ng/mL). In addition, the expression of MALAT-1, HOTAIR, and P-21 was not statistically significant between the two groups. However, a significant reduction in VDR and H19 expression was observed in patients with ALL (p<0.05).

CONCLUSIONS: 25(OH) vitamin D insufficiency was evident in both groups. VDR and H19 signaling might be contributed to the pathogenesis of ALL, which needs further investigations.

PMID:34669855 | DOI:10.1590/1806-9282.20210451