Category: Nevin Manimala

J Clin Gastroenterol. 2021 Jun 11. doi: 10.1097/MCG.0000000000001571. Online ahead of print.

ABSTRACT

BACKGROUND AND GOALS: There is variation in polypectomy techniques for resection of small polyps. Aim was to compare techniques for 4 to 6 mm polyps for recurrent adenoma, efficiency, and adverse events and to establish methodological factors for definitive trial.

MATERIALS AND METHODS: The study was a randomized controlled trial. Outpatients with ≥1, 4 to 6 mm polyps were randomized to cold forceps (CF), cold snare (CS), and hot snare (HS). Polypectomy site was marked with SPOT to assess for recurrence at the original polypectomy site during surveillance colonoscopy. To assess feasibility of a definitive trial we measured (1) rates of patient refusal, participation, ineligibility; (2) retention; (3) recurrent neoplasia; and (4) sample size for a definitive trial.

RESULTS: Three hundred fifty-three patients were randomized to 1 of the 3 polypectomy techniques, of whom 260 (73.6%) completed the initial colonoscopy (mean age 57 y, 50.4% women), with 91, 87, and 82 patients randomized to CF, CS, and HS polypectomy, respectively. Mean time for polyp resection for CF, CS, and HS were 198.8, 58.5, and 96.8 seconds, respectively, with CS and HS requiring less time than CF (P<0.001). One hundred sixty-four (63.1%) completed surveillance colonoscopy. Polyp recurrences were 9 (14.5%) with CF, 5 (9.6%) with CS, and 0 (0%) with HS. Although the recurrence relative risks with CF and CS polypectomy were 1.84 and 1.65 as compared with HS, respectively, neither was statistically significant.

CONCLUSIONS: CS and HS polypectomy require less time than CF. HS polypectomy may have a lower risk for recurrent neoplasia. High attrition rate is a challenge in conducting randomized controlled trial with polyp recurrence as endpoint.

PMID:34115660 | DOI:10.1097/MCG.0000000000001571

J Addict Nurs. 2021 Jun 10. doi: 10.1097/JAN.0000000000000410. Online ahead of print.

ABSTRACT

BACKGROUND: The challenges experienced by mothers supporting an adult child with substance use problems suggest intervention is needed to improve such mothers’ psychosocial well-being through adaptive coping.

AIMS: This study examined beliefs about journaling as well as changes in stress, cortisol levels, and mental health after a 6-week intervention by mothers whose adult children had substance use problems. In addition, the study explored coping methods used and the experience of writing among these mothers.

METHODS: A purposeful sample of 17 mothers completed the pretest and posttest. Participating mothers were asked to make journal entries at least 3 times per week for 6 weeks.

RESULTS: The mothers used diverse adaptive coping methods to manage stress. In particular, they frequently used religious and meaning-focused coping. The mothers perceived journaling as a highly valuable coping method for daily stress. The findings of paired t tests indicated no statistically significant differences in the stress, mental health variables, and cortisol levels between pretest and posttest. However, participants shared the positive experiences of journaling: emotional well-being, stress management, perspective changes, focus, self-regulation, clarity, and gratitude.

CONCLUSION: The present finding suggests journaling is a practical means to promoting adaptive coping in mothers with adult children who have substance use problems.

PMID:34115696 | DOI:10.1097/JAN.0000000000000410

Coron Artery Dis. 2021 Jun 10. doi: 10.1097/MCA.0000000000001080. Online ahead of print.

ABSTRACT

BACKGROUND: Several studies have reported that prophylactic dialysis can reduce the mortality of non-dialysis-dependent chronic kidney disease (CKD) patients after cardiac surgery. However, the results of complications in these randomized controlled trials (RCTs) were not consistent. We aimed to perform a meta-analysis to systematically evaluate the effect of prophylactic dialysis in these non-dialysis-dependent CKD patients.

METHODS: We systematically searched Medline, Embase, Cochrane’s Library and other online sources for related RCTs. Effects of prophylactic dialysis on the incidence of 30 days’ mortality and postoperative complications were analyzed.

RESULTS: Four RCTs comprising 395 patients were included, all of them treated by coronary artery bypass grafting. Treatment of preoperative and intraoperative prophylactic dialysis significantly reduced the rate of 30-day all-cause mortality (risk ratio [RR]: 0.27, 95% confidence interval [CI], 0.13-0.58, P < 0.001, I2 = 0%) and the incidence of pulmonary complications (RR: 0.39, 95% CI, 0.20-0.77, P = 0.007, I2 = 0%), low cardiac output (RR: 0.29, 95% CI, 0.09-0.99, P = 0.05, I2 = 0%), and acute kidney injury (RR: 0.19, 95% CI: 0.07-0.52, P = 0.001, I2 = 0%). However, there were no statistically significant differences between the dialysis group and the control group in gastrointestinal bleeding, sepsis or multiple organ failure, wound infection, arrhythmia, transient neurologic deficit, stroke and re-exploration for bleeding.

CONCLUSION: Prophylactic dialysis can improve the 30-day clinical outcomes of non-dialysis-dependent CKD patients undergoing cardiac surgery, it was associated with the 30-day mortality benefit and led to a decrease in the incidence of pulmonary complications, as well as low cardiac output, and acute kidney injury.

PMID:34115642 | DOI:10.1097/MCA.0000000000001080

Nat Commun. 2021 Jun 10;12(1):3517. doi: 10.1038/s41467-021-23243-4.

ABSTRACT

Epigenome-wide association studies of Alzheimer’s disease have highlighted neuropathology-associated DNA methylation differences, although existing studies have been limited in sample size and utilized different brain regions. Here, we combine data from six DNA methylomic studies of Alzheimer’s disease (N = 1453 unique individuals) to identify differential methylation associated with Braak stage in different brain regions and across cortex. We identify 236 CpGs in the prefrontal cortex, 95 CpGs in the temporal gyrus and ten CpGs in the entorhinal cortex at Bonferroni significance, with none in the cerebellum. Our cross-cortex meta-analysis (N = 1408 donors) identifies 220 CpGs associated with neuropathology, annotated to 121 genes, of which 84 genes have not been previously reported at this significance threshold. We have replicated our findings using two further DNA methylomic datasets consisting of a further >600 unique donors. The meta-analysis summary statistics are available in our online data resource ( www.epigenomicslab.com/ad-meta-analysis/ ).

PMID:34112773 | DOI:10.1038/s41467-021-23243-4

Sci Rep. 2021 Jun 10;11(1):12262. doi: 10.1038/s41598-021-90739-w.

ABSTRACT

Body image disturbance (BID) is a core feature of eating disorders, for which there are few objective markers. We examined the feasibility of a novel digital tool, “Somatomap”, to index BID related to anorexia nervosa (AN) severity. Fifty-five AN inpatients and 55 healthy comparisons (HC) outlined their body concerns on a 2-Dimensional avatar. Next, they indicated sizes/shapes of body parts for their current and ideal body using sliders on a 3-Dimensional avatar. Physical measurements of corresponding body parts, in cm, were collected for reference. We evaluated regional differences in BID using proportional z-scores to generate statistical body maps, and multivariate analysis of covariance to assess perceptual discrepancies for current body, ideal body, and body dissatisfaction. The AN group demonstrated greater regional perceptual inaccuracy for their current body than HC, greater discrepancies between their current and ideal body, and higher body dissatisfaction than HCs. AN body concerns localized disproportionately to the chest and lower abdomen. The number of body concerns and perceptual inaccuracy for individual body parts was strongly associated with Eating Disorder Examination Questionnaire (Global EDE-Q) scores across both groups. Somatomap demonstrated feasibility to capture multidimensional aspects of BID. Several implicit measures were significantly associated with illness severity, suggesting potential utility for identifying objective BID markers.

PMID:34112818 | DOI:10.1038/s41598-021-90739-w

Spinal Cord Ser Cases. 2021 Jun 10;7(1):50. doi: 10.1038/s41394-021-00413-6.

ABSTRACT

STUDY DESIGN: Pre-post intervention.

OBJECTIVES: 1. To test whether replacement of oral anticholinergic (AC) agents with mirabegron for neurogenic lower urinary tract dysfunction (NLUTD) yields improved cognitive function in older persons with spinal cord injury (SCI). 2. To test whether mirabegron is safe and as efficacious as AC.

SETTING: USA.

METHODS: Pilot study: Twenty older (>60 y/o) persons with SCI taking chronic (>6 months) AC medication for NLUTD were enrolled. All participants were first studied on AC at baseline then switched to mirabegron for 6 months. Primary outcomes were cognitive tests of (1) executive function (TEXAS, SDMT); (2) attention (SCWT); and (3) memory (SLUMS and WMS-IV Story A/B). Secondary outcomes assessed efficacy and safety including Neurogenic Bladder Symptom Score (NBSS), bladder diary, neurogenic bowel dysfunction (NBD) survey, heart rate (HR), electrocardiogram (EKG), and mean arterial pressure (MAP).

RESULTS: When switching from AC to mirabegron for NLUTD, older persons with SCI exhibited statistically significant improvements in immediate Story A recall (p = 0.01), delayed story A and B recall (p = 0.01, 0.004), and in TEXAS (p = 0.04). Three subscores within NBSS significantly improved (p = 0.001) and the frequency of incontinence decreased (p = 0.03) on mirabegron. NBD, HR, MAP, and EKGs were unchanged.

CONCLUSIONS: Older persons with SCI on AC for NLUTD demonstrated improved short-term and delayed memory (WMS-IV Story A/B) as well as executive function (TEXAS) when switched to mirabegron. Efficacy of mirabegron for NLUTD symptoms was superior to AC with no adverse effects on bowel or cardiovascular function.

SPONSORSHIP: Claude D. Pepper Older Americans Independence Center.

PMID:34112758 | DOI:10.1038/s41394-021-00413-6

Nat Commun. 2021 Jun 10;12(1):3546. doi: 10.1038/s41467-021-22910-w.

ABSTRACT

The ability to identify segments of genomes identical-by-descent (IBD) is a part of standard workflows in both statistical and population genetics. However, traditional methods for finding local IBD across all pairs of individuals scale poorly leading to a lack of adoption in very large-scale datasets. Here, we present iLASH, an algorithm based on similarity detection techniques that shows equal or improved accuracy in simulations compared to current leading methods and speeds up analysis by several orders of magnitude on genomic datasets, making IBD estimation tractable for millions of individuals. We apply iLASH to the PAGE dataset of ~52,000 multi-ethnic participants, including several founder populations with elevated IBD sharing, identifying IBD segments in ~3 minutes per chromosome compared to over 6 days for a state-of-the-art algorithm. iLASH enables efficient analysis of very large-scale datasets, as we demonstrate by computing IBD across the UK Biobank (~500,000 individuals), detecting 12.9 billion pairwise connections.

PMID:34112768 | DOI:10.1038/s41467-021-22910-w

RMD Open. 2021 Jun;7(2):e001662. doi: 10.1136/rmdopen-2021-001662.

ABSTRACT

OBJECTIVES: Our knowledge about the effect of tocilizumab (TCZ) on the synovium in rheumatoid arthritis (RA) is limited. The aim of this study was to investigate the effect of TCZ on citrullination and on inflammation in the synovial tissue and in the peripheral blood.

METHODS: 15 patients with RA underwent synovial biopsy before and 8 weeks after TCZ initiation. Clinical evaluation was performed at baseline and at 8 weeks. Using immunohistochemistry, we evaluated the expression of CD68, CD3, CD20, osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) before and after treatment with TCZ. We also analysed the expression of protein arginine deiminase (PAD)-2 and PAD-4 enzymes in the synovial tissue and protein citrullination patterns with the help of anticitrullinated protein antibody (ACPA) clones 1325:04C03 and 1325:01B09. Serum levels of interleukin-6 (IL-6), IL-8, RANKL, OPG and C-terminal crosslinked telopeptide type II collagen were measured by ELISA. Paired-wise Wilcoxon signed-rank test was used to compare median values before and after treatment.

RESULTS: Disease activity in patients was reduced from baseline to 8 weeks. Although PAD-2 and PAD-4 expressions remained unchanged after TCZ treatment, the binding of one ACPA clone decreased in the synovial tissue. TCZ did not affect the number of CD68+ macrophages or CD20+ B cells but induced significant decrease in the number of CD3+ T cells. RANKL and OPG expression remained unchanged in the synovial tissue. A significant increase in the levels of IL-6 and RANKL was observed in the serum. This increase was statistically significant in patients who responded to TCZ (achieving Clinical Disease Activity Index low disease activity or remission) but not in non-responders.

CONCLUSIONS: TCZ reduced synovial T-cell counts but not macrophages. A significant increase of serum IL-6 was observed in responders.

PMID:34112702 | DOI:10.1136/rmdopen-2021-001662

Clin Cancer Res. 2021 Jun 10:clincanres.0732.2021. doi: 10.1158/1078-0432.CCR-21-0732. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the effect of sulindac, a non-selective anti-inflammatory drug, for activity to reduce breast density (BD), a risk factor for breast cancer.

EXPERIMENTAL DESIGN: An open-label Phase 2 study was conducted to test the effect of 12 months’ daily sulindac at 150 mg bid on change in percent BD in postmenopausal hormone receptor-positive breast cancer patients on aromatase inhibitor (AI) therapy. Change in percent BD in the contralateral, unaffected breast was measured by non-contrast MRI and reported as change in MRI percent BD (MRPD). A non-randomized patient population on AI therapy (observation group) with comparable baseline BD was also followed for 12-months. Changes in tissue collagen after 6 months of sulindac treatment were explored using second-harmonic generated (SHG) microscopy in a subset of women in the sulindac group who agreed to repeat breast biopsy.

RESULTS: In 43 women who completed 1 year of sulindac (86% of those accrued), relative MRPD significantly decreased by 9.8% (95% CI, -14.6 to -4.7) at 12 months; an absolute decrease of -1.4% (95% CI, -2.5 to -0.3). A significant decrease in mean breast tissue collagen fiber straightness (p=0.032), an investigational biomarker of tissue inflammation, was also observed. MRPD (relative or absolute) did not change in the AI only observation group (N = 40).

CONCLUSIONS: This is the first study to indicate that the NSAID sulindac may reduce BD. Additional studies are needed to verify these findings and determine if prostaglandin E2 inhibition by NSAIDs is important for BD or collagen modulation.

PMID:34112707 | DOI:10.1158/1078-0432.CCR-21-0732

Clin Cancer Res. 2021 Jun 10:clincanres.0474.2021. doi: 10.1158/1078-0432.CCR-21-0474. Online ahead of print.

ABSTRACT

PURPOSE: Patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have poor prognoses. Pyrotinib has shown promising antitumor activity in MBC patients to improve progression-free survival (PFS). However, findings based on real-world data to analyze whether pyrotinib affects overall survival (OS) remain scarce.

EXPERIMENTAL DESIGN: This real-world study is an exploratory analysis of brain metastasis (BM) and the final update of our preceding study of 168 patients with HER2+ MBC. PFS, OS, tumor mutation burden (TMB), clinical benefit rate (CBR) and overall response rate (ORR) were analyzed.

RESULTS: Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants. High TMB was associated with poor OS (P = 0.0072) and PFS (P = 0.0028). In the 39 patients with BM, the median PFS and OS were 8.67 and 13.93 months, respectively. The surgery/radiation (S/R) group of patients with BM had prolonged survival (PFS: 9.97 vs. 7.73 months P = 0.19; OS: 20.67 vs. 12.43 months P = 0.021) compared with the no surgery/no radiation group (NS/NR). The CBR was 58.6% (S/R) vs. 41.4% (NS/NR), while the ORR was 24.1% (S/R) vs. 31.0% (NS/NR).

CONCLUSION: Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort. TMB could be an exploratory biomarker for predicting PFS and OS, but its clinical application still needs further verification.

PMID:34112711 | DOI:10.1158/1078-0432.CCR-21-0474