Nevin Manimala

Birth. 2022 Dec 28. doi: 10.1111/birt.12698. Online ahead of print.

ABSTRACT

The fragility index (FI) is a sensitivity analysis of the statistically significant result of a clinical study. It is the number of hypothetical changes in the primary event of one of the two cohorts in a 1-to-1 comparative trial to render the statistically significant result non-significant (ie, to alter the P-value from ≤0.05 to >0.05). The FI can be compared with the patient drop-out rates and protocol violations, which, if much higher than the FI, may arguably suggest less robustness/stability of the trial’s results. To illustrate the concept, we have chosen the Term Breech Trial (TBT) as a case study. The TBT results favor planned cesarean birth, as opposed to planned vaginal delivery, in the term singleton fetus with breech presentation. Our analysis shows that the FI of the TBT is 21, which is small in comparison to the number (hundreds) of protocol violations present. Some experts have suggested the inclusion of the FI in data analysis and subsequent discussion of clinical trial data. Routine use of such a metric may be valuable in encouraging readers to maintain a healthy degree of skepticism, especially when interpreting trial results which may directly influence clinical practice.

PMID:36576726 | DOI:10.1111/birt.12698

Clin Transl Oncol. 2022 Dec 28. doi: 10.1007/s12094-022-03056-7. Online ahead of print.

ABSTRACT

Gallbladder cancer (GBC) performs strongly invasive and poor prognosis, and adenocarcinoma is the most common histological type in it. Statistically, the 5-year survival rate of patients with advanced GBC is less than 5%. Such dismal outcome might be caused by chemotherapy resistance and native biology of tumor cells, regardless of emerging therapeutic strategies. Early diagnosis, depending on biomarkers, receptors and secretive proteins, is more important than clinical therapy, guiding the pathologic stage of cancer and the choice of medication. Therefore, it is in urgent need to understand the specific pathogenesis of GBC and strive to find promising novel biomarkers for early screening in GBC. Non-coding RNAs (ncRNAs), especially microRNAs (miRNAs, miRs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are confirmed to participate in and regulate the occurrence and development of GBC. Exceptionally, lncRNAs and circRNAs could act as competing endogenous RNAs (ceRNAs) containing binding sites for miRNAs and crosstalk with miRNAs to target regulatory downstream protein-coding messenger RNAs (mRNAs), thus affecting the expression levels of specific proteins to participate in and regulate the development and progression of GBC. It follows that ncRNAs may become promising biomarkers and potential therapeutic targets for GBC. In this review, we mainly summarize the recent research progress of miRNAs and lncRNAs in regulating the development and progression of GBC, chemoresistance, and predicting the prognosis of patients, and highlight the potential applications of the lncRNA/circRNA-miRNA-mRNA cross-regulatory networks in early diagnosis, chemoresistance, and prognostic evaluation, aiming to better understand the pathogenesis of GBC and develop new diagnostic and therapeutic strategies.

PMID:36576705 | DOI:10.1007/s12094-022-03056-7

Infection. 2022 Dec 28. doi: 10.1007/s15010-022-01971-z. Online ahead of print.

NO ABSTRACT

PMID:36576701 | DOI:10.1007/s15010-022-01971-z

Indian J Gastroenterol. 2022 Dec 28. doi: 10.1007/s12664-022-01277-w. Online ahead of print.

ABSTRACT

BACKGROUND: Although studies have proven that liver cirrhosis affects cardiac hemodynamics by means of circulatory overload, they present with definite cardiac functional alteration mostly with end-stage disease. There is limited data on relationship between progression of cirrhosis, cardiac mechanics and sub-clinical dysfunction. This study was done to assess ventricular myocardial mechanics using speckle tracking and deformation imaging among Child-Turcotte-Pugh (CTP) classification A and B cirrhosis.

METHOD: Seventy patients with cirrhosis of Child-Pugh A/B class and sixty-two healthy subjects were prospectively evaluated by standard conventional echocardiography and deformation imaging with rotational echocardiography. Clinical stage of liver cirrhosis was assessed by model for end-stage liver disease (MELD) scores and CTP classification.

RESULTS: Mean ages of patients with cirrhosis and controls were 55.64±14 years and 52.24±12 years, respectively. Though left ventricular (LV) dimensions (end diastolic dimension: 47.27±4.6 mm vs. 45.03±3.8 mm, p = 0.003; end systolic dimension: 30.33±4.9 mm vs. 28.40±2.91 mm, p = 0.006) and volumes (end diastolic volume: 82.08±22.53 mL vs. 68.18±15.75 mL, p = 0.001; end systolic volume: 28.60±8.42 mL vs. 22.18±7.48 mL, p = 0.001) were significantly higher in patients with cirrhosis, mean ejection fraction (EF) by Simpsons method was higher among controls (65.83±5.79% vs. 68.35±5.79%, p = 0.009). Left atrial volume was higher in cirrhosis group indicating presence of diastolic dysfunction (41.24±14.10 mL vs. 26.08±6.4 mL, p = 0.001). Global longitudinal strain as assessed by speckle tracking echocardiography did not show statistical significant difference between two groups (-22.35±4.08% vs. -21.80±2.54%, p = 0.348). Median value of torsion parameters in patients with cirrhosis did not differ compared to controls (torsion in degrees: 2.46 vs. 2.79, p = 0.268).

CONCLUSION: Patients with Child-Pugh A and B stages of cirrhosis present with preserved longitudinal strain, normal torsion but with subtle diastolic dysfunction. Higher MELD score may correlate with increased longitudinal strain possibly due to hyperdynamic state.

PMID:36576699 | DOI:10.1007/s12664-022-01277-w

Indian J Gastroenterol. 2022 Dec 28. doi: 10.1007/s12664-022-01287-8. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to conduct a systematic review and meta-analyses to examine the therapeutic effect of garlic on non-alcoholic fatty liver disease (NAFLD).

METHODS: We searched PubMed, Scopus, Web of Science, and Embase databases for retrieving articles investigating the impact of garlic on NAFLD patients. The comprehensive meta-analysis software version 2.0 was used for statistical analysis. The standardized mean difference with a 95% confidence interval (CI) was reported and the effect size was calculated.

RESULTS: A preliminary search yielded a total of 293 articles. After screening articles based on inclusion criteria, four articles were included in the final analyses. This systematic review included 186 patients with NAFLD. The result of the meta-analysis showed significant differences between the garlic and placebo groups regarding changes in alanine aminotransferase, aspartate aminotransferase, total cholesterol, low-density lipoprotein-cholesterol, triglyceride, and fasting blood sugar. Moreover, the probability of a decrease in hepatic steatosis was 2.75 times lower in the garlic group compared with the placebo group (RR [95% CI]: 2.75 [1.79, 4.23], p-value<0.001).

CONCLUSION: This meta-analysis demonstrates that garlic supplementation had a positive effect on hepatic steatosis, liver enzyme levels, and metabolic profile of patients with NAFLD. However, considering the potential limitation of the included studies, more high-quality clinical trials are needed.

PMID:36576698 | DOI:10.1007/s12664-022-01287-8

Brain Imaging Behav. 2022 Dec 28. doi: 10.1007/s11682-022-00755-1. Online ahead of print.

ABSTRACT

Super typhoons can lead to post-traumatic stress disorder (PTSD), which can adversely affect a person’s mental health after a disaster. Neuroimaging studies suggest that patients with PTSD may have post-exposure abnormalities of the white matter. However, little is known about these defects, if they are localized to specific regions of the white matter fibers, or whether they may be potential biomarkers for PTSD. Typhoon survivors with PTSD (n = 27), trauma-exposed controls (TEC) (n = 33), and healthy controls (HCs) (n = 30) were enrolled. We used automated fiber quantification (AFQ) to process the participants’ DTI and compared diffusion metrics among the three groups. To evaluate diagnostic value, we used support vector machine (SVM) and a random forest (RF) classifier to build a machine learning model. White matter fiber segmentation between the three groups was found to be statistically significant for the fractional anisotropy (FA) value of the right anterior thalamic radiation (ATR) (26-50 nodes) and right uncinate fasciculus (UF) (60-72 nodes) (FDR correction, p < 0.05). By analyzing the characteristics of the machine learning model, the two most important variables were the right ATR and right UF for differentiating PTSD and trauma-exposed controls (TEC) from the healthy controls (HC). In addition, the left cingulum cingulate and left UF were the most critical variables in the differentiation of PTSD and TEC. AFQ with machine learning can localize abnormalities in specific regions of white matter fibers. These regions may be used as a diagnostic biomarker for PTSD.

PMID:36576688 | DOI:10.1007/s11682-022-00755-1

Breast Cancer Res Treat. 2022 Dec 28. doi: 10.1007/s10549-022-06839-2. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to examine the effect of chemotherapy on invasive disease-free survival (iDFS) and overall survival (OS) in a nationwide cohort of patients with estrogen receptor (ER)-negative/human epidermal growth factor receptor 2 (HER2)-negative, T1abN0 breast cancer.

METHODS: Patients with ER-negative/HER2-negative, T1abN0 breast cancer registered in the Danish Breast Cancer Group database between 2007 and 2016 were identified. The effect of adjuvant chemotherapy on iDFS and OS was analyzed with Cox proportional hazards analysis.

RESULTS: In total, 296 patients were included in the statistical analyses. Of these, 235 (79.4%) received chemotherapy and 61 patients (20.6%) did not. Patients treated with chemotherapy were significantly younger, had a significantly higher proportion of grade 3 tumors, T1b tumors, and tumors of ductal subtype. With 7.7 years of median follow-up, treatment with chemotherapy was associated with a significant improvement in OS in the adjusted analysis, Hazard Ratio 0.35 (95% Confidence Interval (0.15-0.81), p = 0.02), chemotherapy vs. no chemotherapy. In the unadjusted analyses, patients with both T1a and T1b tumors had significantly improved OS with chemotherapy. At 5 years, OS was 100% vs. 94.4% and 93.8% vs. 81.3% for patients with T1a and T1b tumors, respectively, chemotherapy vs. no chemotherapy. With 4.9 years of median follow-up, iDFS was not significantly improved with chemotherapy.

CONCLUSION: Patients with ER-negative/HER2-negative, T1abN0 breast cancer had significantly improved OS when treated with chemotherapy. This improvement was significant in patients with both T1a and T1b tumors, respectively. The effect was, however, limited in patients with T1a tumors.

PMID:36576678 | DOI:10.1007/s10549-022-06839-2

Breast Cancer Res Treat. 2022 Dec 28. doi: 10.1007/s10549-022-06836-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Obesity and breast cancer are two major pathologies closely associated with increasing incidence and mortality rates, especially amongst women. The association between both diseases have been thoroughly discussed but much is still to uncover.

AIM: The aim of this study is to analyse tumour characteristics and clinical outcomes of overweight and obese women to disclosure potential associations and better understand the impact of obesity in breast cancer.

MATERIALS AND METHODS: Clinicopathological information of 2246 women were extracted from the institutional database of comprehensive cancer centre in Portugal diagnosed between 2012 and 2016. Women were stratified according to body mass index as normal, overweight, and obese. Patients’ demographic information and tumour features (age, family history, topographic localization, laterality, histological type, and receptor status) were taken as independent variables and overall survival, tumour stage, differentiation grade and bilaterality were considered clinical outcomes.

RESULTS: The main results reveal that overweight and obesity are predominantly associated with worse outcomes in breast cancer patients. Obese patients present larger (p-value: 0.002; OR 1.422; 95% CI 1.134-1.783) and more poorly differentiated tumours (p-value: 0.002; OR 1.480; 95% CI 1.154-1.898) and tend to have lower overall survival although without statistical significance (p-value: 0.117; OR 1.309; 95% CI 0.934-1.833). Overweighted women are more likely to have bilateral breast cancer (p-value: 0.017; OR 3.076; 95% CI 1.225-7.722) than obese women. The results also reveal that overweight women present less distant metastasis (p-value: 0.024; OR 0.525; 95%CI 0.299-0.920). Topographic localization and laterality did not achieve statistical significance.

PMID:36576677 | DOI:10.1007/s10549-022-06836-5

J Immigr Minor Health. 2022 Dec 28. doi: 10.1007/s10903-022-01444-3. Online ahead of print.

ABSTRACT

Our study provides nationally-generalizable evidence on the racial/ethnic and socioeconomic disparities in diagnosis and recovery from childhood behavioral or conduct problems. We pooled data from 4 years (2016-2019) of the National Survey of Children’s Health (NSCH) for 3 to 17 years old US children (N = 114,476). We performed several logistic regression models using complex survey data analysis statistical methodologies to estimate nationally representative and generalizable results in the Stata MP 16 program. About 20.1% of 3-17 years old US children previously diagnosed with behavioral or conduct problems no longer had the current diagnosis (were recovered). Hispanic children [Odds ratio (OR) 0.77, 95% Confidence Interval (CI) 0.65-0-95], immigrant children or children of immigrant parents (first or second generation immigrant children), and children from high-income families [200-399% Federal Poverty Level (FPL)] were about 23%, 38%, and 21% less likely than non-Hispanic White children, children of US native parents, and children with a family income of below 100% FPL to be currently diagnosed with behavioral or conduct problems, respectively. Conversely, Non-Hispanic Black and Hispanic children were about 50% and 40% more likely than non-Hispanic White children to recover from a past diagnosis. Moreover, children from higher-income families (at or above 300% of FPL) were between 1.59 to 1.79 times more likely than those from low-income families (below 100% FPL) to recover from a past diagnosis. Racial/ethnic and socioeconomic disparities in diagnosing appear to persist in recovering from behavioral or conduct problems.

PMID:36576672 | DOI:10.1007/s10903-022-01444-3

Egypt Heart J. 2022 Dec 28;74(1):86. doi: 10.1186/s43044-022-00323-4.

ABSTRACT

BACKGROUND: The most prevalent illness among the elderly is coronary artery disease (CAD), and most of this population present with multi-vessel CAD which constitutes a common management difficulty among elderly people. This study aimed to compare long-term consequences of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) revascularization in elderly patients with multi-vessel coronary artery disease.

RESULTS: This retrospective study evaluated 100 elderly patients with multi-vessel CAD divided into two groups, group 1 the PCI group and group 2 the CABG group. The main findings of the study showed that CABG group had a longer hospital stay than the PCI group (8.16 vs. 2.02 days; P < 0.001). A considerably higher mean residual SYNTAX score was observed in the PCI group than CABG group which was 1.15 and 0.2, respectively (p-value < 0.001). The in-hospital major adverse cardiac events rate (MACE) in both groups was not statistically significant. Regarding the in-hospital mortality rate, although it was higher in the CABG group (6%) versus 2% in the PCI group, yet it was not statistically significant. The long-term MACE in this study revealed that 12.2% of PCI patients had heart failure compared to 6.4% in the CABG group, which was statistically insignificant. In the long-term follow-up, the revascularization rate of CABG group was higher than the PCI group; however, it was statistically insignificant. CABG group had a higher rate of stroke than PCI group being 4.3% and 2%, respectively; yet this difference was not statistically considerable. The long-term mortality rate among the PCI and CABG group was 10.2% and 4.3%, respectively.

CONCLUSIONS: Elderly patients with multi-vessel CAD, PCI with stenting, and CABG were statistically equivalent in long-term death and MI rates, stroke, repeat revascularization. A non-statistically notable distinction between the two groups as regards MACE, composite of death or MI, and all-cause mortality was found. This may have implication on choice of management strategy among elderly patients with multi-vessel CAD.

PMID:36576658 | DOI:10.1186/s43044-022-00323-4