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Nevin Manimala Statistics

The role of inflammatory biomarkers in the association between rheumatoid arthritis and depression: a Mendelian randomization study

Inflammopharmacology. 2023 May 6. doi: 10.1007/s10787-023-01241-w. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammation may mediate the co-pathogenesis of rheumatoid arthritis (RA) and depression because inflammatory cytokines are associated with RA and depression. However, traditional observational research was not able to address problems with residual confusion and reverse causality.

METHODS: We summarized and retrieved 28 inflammatory cytokines associated with RA, depression, or RA with depression through a literature search. The summary statistics from genome-wide association studies for RA, inflammatory biomarkers, broad depression, and major depression disease phenotypes were used. Mendelian randomization was performed to assess the causal association between RA and inflammatory biomarkers, as well as the effects of inflammatory biomarkers on depression. Bonferroni correction was used to reduce the possibility of false positive results.

RESULTS: The study found that evidence for associations of genetically predicted RA was associated with higher levels of interleukin (IL)-9 (OR = 1.035, 95%CI = 1.002-1.068, P = 0.027), IL-12 (OR = 1.045, 95%CI = 1.045-1.014, P = 0.004), IL-13 (OR = 1.060, 95%CI = 1.028-1.092, P = 0.0001), IL-20 (OR = 1.037, 95%CI = 1.001-1.074, P = 0.047), and IL-27 (OR = 1.017, 95%CI = 1.003-1.032, P = 0.021). The level of IL-7 (OR = 1.029, 95%CI = 1.018-1.436, P = 0.030) was significantly related to RA. Only the analysis results between RA and IL-13 were satisfied with the statistical significance threshold corrected by Bonferroni (P < 0.002). However, a causal effect was not found between inflammatory biomarkers and depression.

CONCLUSIONS: In the current study the inflammatory cytokines associated with RA comorbid depression may not be the mediators that directly lead to the co-pathogenesis of RA and depression.

PMID:37148383 | DOI:10.1007/s10787-023-01241-w

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Use of lymph node ratio to guide clinical decision-making concerning adjuvant radiotherapy in pT1-2N1 rectal cancer

Int J Colorectal Dis. 2023 May 6;38(1):115. doi: 10.1007/s00384-023-04415-8.

ABSTRACT

PURPOSE: Lymph node metastases are uncommon in pT1-2 rectal cancer. pT1-2N1 are often characterized with low tumor burden and intermediate prognosis. Therefore, adjuvant radiotherapy (ART) is controversial in these patients. This study aimed to investigate the value of ART in pT1-2 rectal cancer and evaluate the guiding role of lymph node ratio (LNR) for utilization of ART.

METHODS: pT1-2N1 rectal cancer patients who received surgery without neoadjuvant radiotherapy between 2000 and 2018 with at least 12 lymph node harvest were extracted from the Surveillance, Epidemiology and End Results (SEER) database. We used time-dependent receiver operating characteristic (ROC) analysis to determine the optimal cutoff of LNR. Kaplan-Meier methods and Cox proportional hazards regression models were performed to determine the prognostic value of ART in pT1-2N1 rectal cancer patients and subgroups stratified by LNR.

RESULTS: A total of 674 and 1321 patients with pT1N1 and pT2N1 rectal cancer were eligible for analysis. There was no statistical cancer-specific survival (CSS) difference in pT1N1 rectal cancer patients between receiving and not receiving ART (P = 0.464). The 5-year CSS was 89.6% and 83.2% in pT2N1 rectal cancer patients between receiving and not receiving ART, respectively (P = 0.003). A total of 7.0% was identified as the optimal cutoff value of LNR. Survival improvement offered by ART was only found in LNR ≥ 7.0% subgroup (5-year CSS: 89.5% versus 79.6%, P = 0.003) instead of LNR < 7.0% subgroup (5-year CSS: 89.9% versus 86.3%, P = 0.208).

CONCLUSION: ART show substantial survival benefit in pT2N1 rectal cancer patients with LNR ≥ 7.0%, warranting the conventional adoption of ART in this subgroup.

PMID:37148381 | DOI:10.1007/s00384-023-04415-8

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Fragility fracture care gap at a tertiary teaching hospital in Malaysia

Arch Osteoporos. 2023 May 6;18(1):63. doi: 10.1007/s11657-023-01256-4.

ABSTRACT

Fracture begets fracture, pharmacological treatment is needed to prevent secondary fractures. This study found that there was a fragility fracture care gap where both bone health investigations and treatment initiation rates were low. Strategies such as Fracture Liaison Service is needed to address the care gap.

PURPOSE: This study aimed to investigate the clinical burden and secondary fracture prevention of fragility fractures at a tertiary teaching hospital in Malaysia.

METHODS: Electronic medical records of all patients admitted with fragility fractures between 1 January 2017-31 December 2018 were reviewed. Patients < 50 years old, with non-fragility fractures, restricted access to medical records, transferred to another hospital or who passed away during admission were excluded. Descriptive statistics were used to summarise patients’ characteristics, frequency of fragility fractures, and secondary fracture prevention details. Binomial logistic regression was performed to analyse predictive factors for post-fracture bone health assessments and treatment initiation.

RESULTS: 1030 patients [female (767/1030, 74.5%)] presented with 1071 fractures [hip fractures (378/1071, 35.3%)]. 170/993 (17.1%) patients were initiated on anti-osteoporosis medications (AOMs) and 148/984 (15.0%) had bone mineral density (BMD) performed within 1-year post-fracture. Less than half (42.4%) of the patients remained on treatment at 1-year post-fracture. Older patients [65-74 years old: odds ratio (OR) = 2.18, 95%CI 1.05-4.52, p = 0.04; ≥ 75 years: OR = 3.06, 95%CI 1.54-6.07, p < 0.01], hip fractures (OR = 1.95, 95%CI 1.23-3.11, p < 0.01), Chinese ethnicity (OR = 1.90, 95%CI 1.07-3.35, p = 0.03),previously diagnosed with osteoporosis (OR = 2.65, 95%CI:1.32-5.31, p < 0.01) and a BMD test performed (OR = 12.48, 95%CI 8.04-19.37, p < 0.01) were found to have higher AOM initiation. Patients with past diagnosis of osteoporosis (OR = 4.45, 95%CI 2.25-8.81, p < 0.01) and initiated on AOM (OR = 11.34, 95%CI 7.57-16.97, p < 0.01) had a higher likelihood to undergo BMD testing.

CONCLUSION: The AOM initiation and BMD testing rates were low. There is a need to address the fragility fracture care gap with strategies such as Fracture Liaison Service.

PMID:37148374 | DOI:10.1007/s11657-023-01256-4

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The whole-cell proteome shows the characteristics of macrolides-resistant Bordetella pertussis in China linked to the biofilm formation

Arch Microbiol. 2023 May 6;205(6):219. doi: 10.1007/s00203-023-03566-0.

ABSTRACT

The macrolides-resistant Bordetella pertussis (MR-Bp) isolates in China evolved from the ptxP1/fhaB3 allele and rapidly became predominant, suggestive of an adaptive transmission ability. This was different from the global prevalent ptxP3 strains, in which MR-Bp was rarely reported. The study aimed to determine the underlying mechanism responsible for fitness and resistance in these two strains. We identify proteomic differences between ptxP1/fhaB3 and ptxP3/fhaB1 strains using tandem mass tag (TMT)-based proteomics. We then performed in-depth bioinformatic analysis to determine differentially expressed genes (DEGs), followed by gene ontology (GO), and protein-protein interaction (PPI) network analysis. Further parallel reaction monitoring (PRM) analysis confirmed the expression of four target proteins. Finally, the crystal violet method was used to determine biofilm-forming ability. The results showed that the main significantly different proteins between the two represent isolates were related to biofilm formation. Furthermore, we have confirmed that ptxP1/fhaB3 showed hyperbiofilm formation in comparison with ptxP3/fhaB1. It is suggested that the resistance and adaptability of ptxP1/fhaB3 strains may be related to the formation of biofilm through proteomics. In a word, we determined the significantly different proteins between the ptxP1/fhaB3 and ptxP3/fhaB1 strains through whole-cell proteome, which were related to biofilm formation.

PMID:37148370 | DOI:10.1007/s00203-023-03566-0

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The power of TOPMed imputation for the discovery of Latino-enriched rare variants associated with type 2 diabetes

Diabetologia. 2023 May 6. doi: 10.1007/s00125-023-05912-9. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population.

METHODS: We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort.

RESULTS: Compared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37, p=3.4 × 10-9). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance.

CONCLUSIONS/INTERPRETATION: Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores.

DATA AVAILABILITY: Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).

PMID:37148359 | DOI:10.1007/s00125-023-05912-9

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Nevin Manimala Statistics

Physicochemical and histological analysis of an experimental endodontic repair material containing 45S5 bioactive glass

Biotechnol Lett. 2023 May 6. doi: 10.1007/s10529-023-03391-x. Online ahead of print.

ABSTRACT

This study aimed to evaluate the maximum compressive strength, the modulus of elasticity, pH variation, ionic release, radiopacity and biological response of an experimental endodontic repair cement based on 45S5 Bioglass®. An in vitro and in vivo study with an experimental endodontic repair cement containing 45S5 bioactive glass was conducted. There were three endodontic repair cement groups: 45S5 bioactive glass-based (BioG), zinc oxide-based (ZnO), and mineral trioxide aggregate (MTA). In vitro tests were used to evaluate their physicochemical properties: compressive strength, modulus of elasticity, radiopacity, pH variation, and the ionic release of Ca+ and PO4. An animal model was used to evaluate the bone tissue response to endodontic repair cement. Statistical analysis included the unpaired t-test, one-way ANOVA and Tukey’s test. BioG showed the lowest compressive strength and ZnO showed the highest radiopacity among the groups, respectively (p < 0.05). There were no significant differences in the modulus of elasticity among the groups. BioG and MTA maintained an alkaline pH during the 7 days of evaluation, both at pH 4 and in a pH 7 buffered solutions. PO4 was elevated in BioG, peaking at 7 days (p < 0.05). Histological analysis showed less intense inflammatory reactions and new bone formation in MTA. BioG showed inflammatory reactions that decreased over time. These findings suggest that the BioG experimental cement had good physicochemical characteristics and biocompatibility required for bioactive endodontic repair cement.

PMID:37148343 | DOI:10.1007/s10529-023-03391-x

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Five-Factor Modified Frailty Index as a Predictor of Complications Following Total Ankle Arthroplasty

Foot Ankle Spec. 2023 May 6:19386400231169368. doi: 10.1177/19386400231169368. Online ahead of print.

ABSTRACT

INTRODUCTION: Ankle arthritis adversely affects patients’ function and quality of life. Treatment options for end-stage ankle arthritis include total ankle arthroplasty (TAA). A 5-item modified frailty index (mFI-5) has predicted adverse outcomes following multiple orthopaedic procedures; this study evaluated its suitability as a risk-stratification tool in patients undergoing TAA.

METHODS: The National Surgical Quality Improvement Program (NSQIP) database was retrospectively reviewed for patients undergoing TAA between 2011 and 2017. Bivariate and multivariate statistical analyses were performed to investigate frailty as a possible predictor of postoperative complications.

RESULTS: In total, 1035 patients were identified. When comparing patients with an mFI-5 score of 0 versus ≥2, overall complication rates significantly increased from 5.24% to 19.38%, 30-day readmission rate increased from 0.24% to 3.1%, adverse discharge rate increased from 3.81% to 15.5%, and wound complications increased from 0.24% to 1.55%. After multivariate analysis, mFI-5 score remained significantly associated with patients’ risk of developing any complication (P = .03) and 30-day readmission rate (P = .005).

CONCLUSIONS: Frailty is associated with adverse outcomes following TAA. The mFI-5 can help identify patients who are at an elevated risk of sustaining a complication, allowing for improved decision-making and perioperative care when considering TAA.

LEVELS OF EVIDENCE: III, Prognostic.

PMID:37148165 | DOI:10.1177/19386400231169368

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Assessment of biological effect of nab-paclitaxel combined with gemcitabine, using contrast enhanced ultrasonography and elastography, in advanced pancreatic ductal carcinoma: A single-center pilot study

Endosc Ultrasound. 2023 Mar-Apr;12(2):273-276. doi: 10.4103/EUS-D-22-00040.

ABSTRACT

EUS associated with contrast-enhanced harmonic EUS (CH-EUS) and EUS elastography (EUS-E) are used in clinical practice to assess pancreatic tumor at the diagnosis. In case of pancreatic ductal adenocarcinoma (PDAC) with liver metastasis, nab-paclitaxel combined with gemcitabine is a first-line treatment option. We aimed to assess the modification of PDAC microenvironment induced by the combination of nab-paclitaxel with gemcitabine, by endoscopic ultrasonography techinics. This single center phase III study conducted between February 2015 and June 2016 included patients with pancreatic adenocarcinoma with mesurable liver metastasis and no prior cancer treatment fit for two cycles of nab-paclitaxel combined with gemcitabine. We aimed to perform EUS with CH-EUS and EUS-E of the pancreatic tumor, CT scan and contrast enhanced ultrasonogram (CE-US) of a reference liver metastasis, before and after the two cylces of chemotherapy. Primary end point was modification of vascularizaion of primary tumor and a reference liver metastasis. Secondary end points were modification of stromal content, safety profile of drug combination and tumor response rate. Sixteen patients were analyzed, but only 13 received two cycled of chemotherapy (CT) (toxicity [n = 1] or death [n = 2]). There was no statistical modification induced by CT concering vascularity of primary tumor (time to maximum intensity P = 0.24, value of maximum intensity P = 0.71, hypoechogenic aspect generated by injection of contrast enhancing agent), vascularity of a reference liver metastasis (time to maximum intensity P = 0.99, value of maximum intensity P = 0.71) and tumor elasticity (P = 0.22). Eleven patients had tumor response assessement, 6/11 (54%) had measurable disease response 4/11 (36%) with partial responses and 2/11 (18%) with stable disease. All other patients showed disease progression. No serious side effects occurred, 6/11 patients had a dose adjustment. We did not show significant modification of vascularity and elasticity but these results should be taken with caution because of important limitations.

PMID:37148140 | DOI:10.4103/EUS-D-22-00040

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Mean quality of life of hypertensive and diabetic patients: A comparative study of patients in secondary and tertiary health facilities in Kaduna State, Nigeria

Niger Postgrad Med J. 2023 Apr-Jun;30(2):167-174. doi: 10.4103/npmj.npmj_5_23.

ABSTRACT

INTRODUCTION: Hypertension and diabetes have become major non-communicable diseases of public health importance globally, considering the magnitude of the diseases, the propensity to worsen the patients’ quality of life and the associated mortality. This study compared the health-related quality of life (HRQOL) of hypertensive and diabetic patients in both tertiary and secondary health facilities in Kaduna State, north-western Nigeria.

MATERIALS AND METHODS: This was a descriptive comparative cross-sectional study amongst 325 patients, of which 93 (28.6%) were from the tertiary and 232 (71.4%) were from the secondary facilities. All eligible respondents participated in this study. Data were analysed with SPSS version 25 and STATA SE 12, t-test for comparison of two means, Chi-square and multivariate analyses were performed with P < 0.05.

RESULTS: The mean age was 55.72 ± 13 years. Two-thirds, 197 (60.6%), were hypertensive only, 60 (18.5%) were diabetic only (18.5%) and 68 (20.9%) were hypertensive diabetic. For the hypertensive only at the tertiary facility, the mean scores for vitality (VT) (68.0 ± 5.97, P = 0.01), emotional well-being (EW) (77.33 ± 4.52, P = 0.0007) and bodily pain (BP), (74.17 ± 5.94, P = 0.05) were significantly higher for tertiary compared with those at secondary facilities. The mean HRQOL for the people with diabetes only at the tertiary facilities also showed statistically significant higher scores for VT (72.2 ± 61, P = 0.01), social functioning (72.2 ± 8.4, P = 0.02), EW (75.44 ± 4.9, P = 0.001) and BP (85.56 ± 7.7, P = 0.01) when compared with the secondary facilities.

CONCLUSION: Patients managed by specialists at the tertiary health facility had better HRQOL than those managed at the secondary health facilities. Continued medical education and the use of standard operating procedures are recommended for improved HRQOL.

PMID:37148121 | DOI:10.4103/npmj.npmj_5_23

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Serum magnesium levels of term neonates with birth asphyxia and relationship to severity of asphyxia

Niger Postgrad Med J. 2023 Apr-Jun;30(2):161-166. doi: 10.4103/npmj.npmj_1_23.

ABSTRACT

BACKGROUND AND AIMS: Birth asphyxia is one of the three main causes of neonatal mortality in Nigeria. Hypomagnesaemia has been reported amongst severely asphyxiated babies. Despite this, the prevalence of hypomagnesaemia amongst newborns with birth asphyxia has not been well researched in Nigeria. This study set out to determine the prevalence of hypomagnesaemia in term neonates with birth asphyxia and the relationship (if any) between magnesium levels and the severity of birth asphyxia or encephalopathy.

METHODS: In this cross-sectional analytical study, the serum magnesium levels of consecutive cases of birth asphyxia were compared to that of gestational age-matched healthy term neonates. Babies with Apgar scores <7 in the 5th minute of life were recruited into the study. Blood samples were taken from each baby at birth and 48 h. Serum magnesium was measured using spectrophotometry.

RESULTS: Hypomagnesaemia was found in 36 (35.3%) babies with birth asphyxia and 14 (13.7%) healthy controls; this difference was statistically significant (χ2 = 18.098, P = 0.001), with an odds ratio of 3.4 (95% confidence interval = 1.7, 6.9). The median (interquartile range) levels of serum magnesium in babies with mild, moderate and severe asphyxia were 0.7 mmol/L (0.5-1.1), 0.7 mmol/L (0.4-0.9) and 0.7 mmol/L (0.5-1.0), respectively (P = 0.316), while those of babies with mild (stage 1), moderate (stage 2) and severe (stage 3) encephalopathy were 1.2 mmol/L (1.0-1.3), 0.7 mmol/L (0.5-0.8) and 0.8 mmol/L (0.6-1.0), respectively (P = 0.789).

CONCLUSION: This study has shown that hypomagnesaemia was more common in babies with birth asphyxia and there was no relationship between magnesium levels and the severity of asphyxia or encephalopathy.

PMID:37148120 | DOI:10.4103/npmj.npmj_1_23