Nevin Manimala

Elife. 2021 Jun 23;10:e69454. doi: 10.7554/eLife.69454. Online ahead of print.

ABSTRACT

Targeting DNA repair pathway offers an important therapeutic strategy for Homo sapiens (human) cancers. However, the failure of DNA repair inhibitors to markedly benefit patients necessitates the development of new strategies. Here, we show that exosome component 1 (EXOSC1) promotes DNA damages and sensitizes human kidney renal clear cell carcinoma (KIRC) cells to DNA repair inhibitor. Considering that endogenous source of mutation (ESM) constantly assaults genomic DNA and likely sensitize human cancer cells to the inhibitor, we first analyzed the statistical relationship between the expression of individual genes and the mutations for KIRC. Among the candidates, EXOSC1 most notably promoted DNA damages and subsequent mutations via preferentially cleaving C site(s) in single-stranded DNA. Consistently, EXOSC1 was more significantly correlated with C>A transversions in coding strands than these in template strands in human KIRC. Notably, KIRC patients with high EXOSC1 showed a poor prognosis, and EXOSC1 sensitized human cancer cells to poly(ADP-ribose) polymerase inhibitor. These results show that EXOSC1 acts as an ESM in KIRC, and targeting EXOSC1 might be a potential therapeutic strategy.

PMID:34159897 | DOI:10.7554/eLife.69454

Gut Microbes. 2021 Jan-Dec;13(1):1930872. doi: 10.1080/19490976.2021.1930872.

ABSTRACT

Bariatric surgery induces significant shifts in the gut microbiota which could potentially contribute to weight loss and metabolic benefits. The aim of this study was to characterize a microbial signature following Roux-en-Y Gastric bypass (RYGB) surgery using novel and existing gut microbiota sequence data. We generated 16S rRNA gene and metagenomic sequences from fecal samples from patients undergoing RYGB surgery (n = 61 for 16S rRNA gene and n = 135 for metagenomics) at pre-surgical baseline and one, six, and twelve-month post-surgery. We compared these data with three smaller publicly available 16S rRNA gene and one metagenomic datasets from patients who also underwent RYGB surgery. Linear mixed models and machine learning approaches were used to examine the presence of a common microbial signature across studies. Comparison of our new sequences with previous longitudinal studies revealed strikingly similar profiles in both fecal microbiota composition (r = 0.41 ± 0.10; p < .05) and metabolic pathways (r = 0.70 ± 0.05; p < .001) early after surgery across multiple datasets. Notably, Veillonella, Streptococcus, Gemella, Fusobacterium, Escherichia/Shigella, and Akkermansia increased after surgery, while Blautia decreased. Machine learning approaches revealed that the replicable gut microbiota signature associated with RYGB surgery could be used to discriminate pre- and post-surgical samples. Opportunistic pathogen abundance also increased post-surgery in a consistent manner across cohorts. Our study reveals a robust microbial signature involving many commensal and pathogenic taxa and metabolic pathways early after RYGB surgery across different studies and sites. Characterization of the effects of this robust microbial signature on outcomes of bariatric surgery could provide insights into the development of microbiome-based interventions for predicting or improving outcomes following surgery.

PMID:34159880 | DOI:10.1080/19490976.2021.1930872

Ann Med. 2021 Dec;53(1):890-899. doi: 10.1080/07853890.2021.1921838.

ABSTRACT

BACKGROUND: We carried out this study to demonstrate the effects of outcome sensitivity, participant exclusions, and covariate manipulations on results of the epidemiological analysis of coronary heart disease (CHD) and its behaviour-related risk factors.

MATERIAL AND METHODS: Our study population consisted of 1592 54-year-old men, who participated in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. We used the Cox proportional-hazards model to predict the hazard of CHD and applied different sets of outcomes concerning outcome sensitivity and data preprocessing procedures regarding participant exclusions and covariate manipulations.

RESULTS: The mean follow-up time was 23 years, and 730 men received the CHD diagnosis. Cox regressions based on data with no participant exclusions most often discovered statistically significant associations. Loose inclusion criteria for study participants with any CVD during the follow-up and strict exclusion criteria for participants with no CVD were best in discovering the associations between risk factors and CHD. Outcome sensitivity affected the associations, whereas the covariate type, continuous or categorical, did not.

CONCLUSIONS: This study suggests that excluding study participants who are not disease-free at baseline is probably unnecessary for epidemiological analyses. Epidemiological research reports should present results based on no data exclusions together with results based on reasoned exclusions.

PMID:34159863 | DOI:10.1080/07853890.2021.1921838

Chronic Illn. 2021 Jun 23:17423953211023964. doi: 10.1177/17423953211023964. Online ahead of print.

ABSTRACT

OBJECTIVE: Instrumental activities of daily living (IADL) are important for managing multiple chronic conditions (MCC) and maintaining independence while aging. Using data from the National Health and Aging Trends Study (NHATS), we answered the question: are there differences in ability and performance of IADL among groups of older adults with 0-1 (no MCC), 2-4 (low MCC), and 5+ chronic conditions (multisystem morbidity: MM)?

METHODS: Cross-sectional study using Poisson regression and incidence rate ratios. Participants were 6,019 community-dwelling older adults who regularly take medications. We derived composite variables for ability and performance of IADL; MCC groups were based on count of 11 chronic conditions.

RESULTS: Older adults with MM had lower IADL count for ability (IRR = .81) and performance (IRR = .77), and MM group significantly predicted both ability and performance of IADL (p < .001); ‘low MCC’ group was not significantly different than ‘no MCC’ regarding disability.

DISCUSSION: Having MM is statistically and clinically different than having low MCC or no MCC; 5+ chronic conditions may be a meaningful inclusion criterion for interventions to decrease disability and 2-4 chronic conditions may be better for trials to prevent disability. Researchers should measure both ability and performance of daily activity.

PMID:34159840 | DOI:10.1177/17423953211023964

Global Spine J. 2021 Jun 23:21925682211019696. doi: 10.1177/21925682211019696. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective cohort study.

OBJECTIVE: To (1) define utilization trends for navigated instrumented posterior lumbar fusion (PLF), (2) compare reasons and rates of revision at 30-day, 60-day, 90-day, and 1-year follow-up, and (3) compare 90-day perioperative complications between navigated versus conventional instrumented PLF.

METHODS: Patients who underwent navigated or conventional instrumented PLF were identified from the Humana insurance database using the PearlDiver Patient Records between 2007-2017. Usage of navigation was characterized. Patient demographics and operative characteristics (number of levels fused, interbody usage) were compared between the 2 treatment groups. Propensity score matching was done and comparisons were made for revision rates at different follow-up periods (categorized by reasons) and other 90-day perioperative complications.

RESULTS: This study included 1,648 navigated and 23 429 conventional instrumented PLF. Navigated cases increased over the years studied to approximately 10% in 2017. Statistical analysis after propensity score matching revealed significantly lower rates of hardware-related revision at 90-day follow-up in the navigated cohort (0.49% versus 1.15%, P = .033). At 1-year follow-up, the navigated cohort continued to have significantly lower rates of hardware-related revision (1.70% versus 2.73%, P = .044) as well as all cause revision (2.67% versus 4.00%, P = .032). There were no statistical differences between the 2 cohorts in any of the 90-day perioperative complications studied, such as cellulitis and blood transfusion (P > .05 for all).

CONCLUSIONS: These findings suggest that navigation is associated with reductions in hardware-related revisions after instrumented PLF. However, these results should be interpreted cautiously in the setting of potential confounding by other unmeasured variables.

PMID:34159837 | DOI:10.1177/21925682211019696

Clin Nurs Res. 2021 Jun 23:10547738211024797. doi: 10.1177/10547738211024797. Online ahead of print.

ABSTRACT

This study aimed to evaluate the efficacy of Benson’s relaxation technique on anxiety and depression among patients undergoing hemodialysis. A systematic review of randomized controlled trials was conducted. Searching databases included EBSCO Host, PubMed, ProQuest, Science Direct, Sage Journals, Ovid, and Google Scholar from January 2000 to September 2020. Five randomized controlled trials were identified. Findings revealed a statistically significant decrease in anxiety score. Concerning depression; one RCT showed a statistically significant decrease and two RCTs revealed a non-significant difference in depression level. The overall quality of the RCTs was not high. Despite that the RCTs showed benefits of BRT in managing anxiety. However, this is not the same for depression. The lack of high-quality scientific evidence supporting its retinue use indicates that additional well designed randomized controlled trials in multiple countries are warranted to support the efficacy of Benson’s relaxation technique on anxiety and depression among patients undergoing hemodialysis.

PMID:34159828 | DOI:10.1177/10547738211024797

Can Assoc Radiol J. 2021 Jun 23:8465371211020630. doi: 10.1177/08465371211020630. Online ahead of print.

ABSTRACT

PURPOSE: Assess quality metrics of modified barium swallow studies (MBSS) with and without a radiologist present during the procedure.

METHODS: Retrospective review of MBSS performed on adult inpatients at a tertiary care hospital 6-months pre- and post-institutional change from having to not having a radiologist present during the examination.

FACTORS ASSESSED INCLUDED: fluoroscopy time; study duration; number of cine loops; number of images; efficiency of collimation (using a 5-point scoring system); time to final report; radiologist-speech language pathologist report disagreement; and recalls for inadequate studies. Statistical analysis was via Welch’s t-test and a test of proportions for continuous and count data under the normal approximation.

RESULTS: 106 and 119 MBSS were analyzed from the radiologist present and radiologist absent periods, respectively. No statistically significant differences were found for: average fluoroscopy time (116.1 s vs. 126.9 s; P = 0.161); study duration (400.4 s vs. 417.3 s; P = 0.453); number of cine loops (9.3 vs. 10.2; P = 0.075); number of images (620.5 vs. 581.1; P = 0.350); or report disagreement. There was improved performance without the radiologist present for collimation (1.92 vs. 1.43; P = 0.003) and fewer non-diagnostic images (6.5 vs. 4.5; P = 0.001). Time to final report was longer with the radiologist absent due to more reports with significant delays. There were no repeated studies because of inadequate technique in either group.

CONCLUSION: MBSS performed by technologists without radiologist supervision is not inferior to those performed with radiologist supervision on multiple performance measures. This supports technologist operated MBSS without radiologist supervision, while acknowledging a need to further address radiologist report time delay.

PMID:34159812 | DOI:10.1177/08465371211020630

Am J Hosp Palliat Care. 2021 Jun 23:10499091211026675. doi: 10.1177/10499091211026675. Online ahead of print.

ABSTRACT

BACKGROUND: A critical aspect of pediatric palliative care consultations is the assessment and documentation of patient and family needs. While these assessments usually include a focus on physical pain, there is less standardization of assessments of other physical symptoms and psychosocial, emotional, or spiritual needs.

AIMS: To improve the breadth of assessment of psychosocial and emotional needs, screen for symptoms other than pain among pediatric patients utilizing palliative care services, and to increase documentation of assessment data from 30%-40% to 80% through practice changes implemented in 2 Plan-Do-Study-Act (PDSA) cycles.

METHODS: This quality improvement project involved implementing provider education and adapting the palliative care consultation template in the electronic health record to improve breadth and consistency of assessment and documentation during consultations by the interdisciplinary pediatric palliative care team. Two PDSA cycles were performed. Chi squared tests and statistical control charts were used for data analysis.

RESULTS: There was statistically significant improvement in the inclusion of documentation of a pediatric palliative care social work note from baseline (32%) to Cycle 2 (57%). Physical symptom screening declined slightly, but not significantly (p = .32) and socio-emotional discussions also declined but not significantly (p = .05).

CONCLUSIONS: Screening for physical symptoms and discussions with patients and families about psychosocial/emotional needs during the initial palliative care consultations are extremely important in providing effective, holistic, patient-centered care. There is a need for development of pediatric-centric guidelines and quality measures to evaluate pediatric palliative care programs; further research is indicated to determine methods for evaluating compliance with these guidelines.

PMID:34159810 | DOI:10.1177/10499091211026675

J Plast Reconstr Aesthet Surg. 2021 Apr 18:S1748-6815(21)00194-7. doi: 10.1016/j.bjps.2021.03.090. Online ahead of print.

ABSTRACT

OBJECTIVES: Mandibular defects involving the central segment are challenging. This study analyzes the impact of defect extent and reconstruction method on quality of life (QOL) and obstructive sleep apnea (OSA).

MATERIALS AND METHODS: Twenty-nine ameloblastoma patients received segmental mandibulectomy involving the C-segment and immediate fibula free flap reconstruction were recruited. Defects: (C: 2, LC: 11, LCL: 19). Mean defect length: 8.79 cm (± 2.34). Inset: Low-single-barrel (n: 19), with secondary distraction osteogenesis (n: 8/19), high-single-barrel (n: 7), double barrel (n: 3). Patients were surveyed using University of Washington Quality of Life (UW-QOL) and Berlin risk of postoperative sleep apnea questionnaires.

RESULTS: Flap failure: None. Mean follow-up: 109.6 ± 92.8 months.

UW-QOL: Physical function 91.83 (± 14.92); social function 90.17 (± 17.19). No statistical difference between C, LC, and LCL was found, but C group which received low-single-barrel had the lowest score in appearance and chewing domains. In health-related QOL (HR-QOL) compared with 1 month before cancer, 69% reported best results. “Appearance” was the most important issue for the past 7 days, followed by “Chewing,” prevailing in LC and C groups that predominately reconstructed by low-single-barrel. Berlin score: 7 patients (4 LCL, 3 LC≥8 cm) were at high risk for postoperative OSA.

CONCLUSION: “Like-with-like” reconstruction with immediate endosteal dental implants yields the best results. Inset of fibula bone could affect outcomes, favoring double-barrel or single-high-barrel inset. Appearance and chewing remain the main concerns, largely, in those with low-single-barrel inset and no dental restoration. After long/extensive LCL and LC mandibulectomies, postoperative OSA warrants further investigation, and modification of resection/reconstruction techniques.

PMID:34158274 | DOI:10.1016/j.bjps.2021.03.090

J Plast Reconstr Aesthet Surg. 2021 Apr 24:S1748-6815(21)00153-4. doi: 10.1016/j.bjps.2021.03.062. Online ahead of print.

ABSTRACT

BACKGROUND: The effect of Botulinum toxin type A (BTX-A) in treating or preventing a hypertrophic scar (HS) had been reported in clinical studies. However, the dose-effect relationship remains unclear.

OBJECTIVE: To study the dose-effect relationship of BTX-A intralesional monotherapy treating human HS.

METHODS: Six HS tissues were collected from six patients. Each tissue was segmented into 24 specimens and split into four groups: negative control (group A), 0.5U BTX-A (group B), 1U BTX-A (group C), and 2U BTX-A (group D). Six nude mice, each was prepared by implanting four specimens (one from each group) into the back for a total of 24 specimens. The process mentioned above were repeated six times. A re-entry operation was performed to obtain the specimens after 8 weeks. The weight of HS, the expression of decorin and TGF-β₁, the proliferation, and migration ability of hypertrophic scar fibroblasts (HSFBs) were compared among groups.

RESULTS: The weight of HS, the expression of decorin and TGF-β₁, the proliferation, and migration ability of HSFBs showed significant differences in groups C and D as compared to group A; there has been no statistical significance in group B.

CONCLUSION: BTX-A showed significant therapeutic efficacy when compared with the negative control group in a dose-dependent manner. BTX-A can reduce the weight of HS, upregulate the expression of decorin, downregulate the expression of TGF-β₁, and inhibit HSFBs proliferation and migration ability. This study indicates that BTX-A intralesional monotherapy treating HS should reach a threshold dose to achieve an effective treatment, and a high dose of BTX-A is more effective than a low dose.

PMID:34158272 | DOI:10.1016/j.bjps.2021.03.062