A prospective study of the adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers

Background A diverse and abundant gut microbiome can improve cancer patients’ treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT. Materials and methods Rectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. 42 of these patients received antibiotics during the study period. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size. Results Gut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; all P <0.01), but were at or near baseline levels in 60% of patients by week 12. Patients with higher gut diversity at baseline had the steepest decline in gut microbiome diversity. Gut microbiome composition was significantly altered during CRT, with increases in Proteobacteria and decreases in Clostridiales, but adapted after CRT, with increases in Bacteroides species. Conclusion After CRT, the diversity of the gut microbiomes in this population tended to return to baseline levels by the 12 week follow-up period, but structure and composition remained significantly altered. These changes should be considered when designing studies to analyze the gut microbiome in patients who receive pelvic CRT for gynecologic cancers.

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Adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers

10.1101/2020.04.10.036426 ◽

2020 ◽

Author(s):

Molly B. El Alam ◽

Travis T. Sims ◽

Ramez Kouzy ◽

Greyson W. G. Biegert ◽

Joseph Abi Jaoude ◽

...

Keyword(s):

Gut Microbiome ◽

Repeated Measures ◽

Diversity Index ◽

Marker Gene ◽

Hypervariable Region ◽

Rrna Gene ◽

Gynecologic Cancers ◽

Linear Discriminant ◽

Baseline Levels ◽

Over Time

ABSTRACTBackgroundA diverse and abundant gut microbiome can improve cancer patients’ treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT.Materials and MethodsRectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size.ResultsGut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; all P <0.01), but were at or near baseline levels in 60% of patients by week 12. Patients with higher gut diversity at baseline had the steepest decline in gut microbiome diversity. Gut microbiome composition was significantly altered during CRT, with increases in Proteobacteria and decreases in Clostridiales, but adapted after CRT, with increases in Bacteroides species.ConclusionAfter CRT, the gut microbiome’s diversity tends to return to baseline levels, but its structure and composition remain significantly altered. These changes should be considered when designing studies to analyze the gut microbiome as a predictive or prognostic biomarker in patients who receive pelvic CRT for gynecologic cancers.

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CAN POLYARTICULAR ULTRASOUND PREDICT THE DEVELOPMENT OF PSORIATIC ARTHRITIS OVER TIME? – A PROSPECTIVE STUDY WITH 4 YEARS OF FOLLOW-UP

10.5151/sbr2019-355 ◽

2019 ◽

Author(s):

BARBARA CARVALHO KLEMZ ◽

KARINE RODRIGUES LUZ ◽

ADRIANA MARIA PORRO ◽

POLIANNA OLIVEIRA MATOS SOARES ◽

MARCELO MEDEIROS PINHEIRO

Keyword(s):

Psoriatic Arthritis ◽

Prospective Study ◽

A Prospective Study ◽

Over Time

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The Impact of Overnight Orthokeratology on Accommodative Response in Myopic Subjects

Journal of Clinical Medicine ◽

10.3390/jcm9113687 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3687

Author(s):

Ana F. Pereira-da-Mota ◽

Jéssica Costa ◽

Ana Amorim-de-Sousa ◽

José M. González-Méijome ◽

António Queirós

Keyword(s):

Repeated Measures ◽

Friedman Test ◽

Repeated Measures Anova ◽

Accommodative Response ◽

Baseline Levels ◽

Accommodative Lag ◽

Objectively Measured ◽

The Impact ◽

Lens Wear ◽

Over Time

This study aimed to evaluate the effects of two months of orthokeratology (OK) treatment in the accommodative response of young adult myopes. Twenty eyes (21.8 ± 1.8 years) were fitted with the Paragon CRT® 100 LENS to treat myopia between −1.00 and −2.00 D. Low- and high-contrast visual acuity (LCDVA and HCDVA), central objective refraction, light disturbance (LD), and objective accommodative response (using the Grand Seiko WAM-5500 open-field autorefractometer coupled with a Badal system) were measured at baseline (BL) before lens wear and after 1, 15, 30, and 60 nights of OK. Refractive error correction was achieved during the first fifty days of OK lens wear, with minimal changes afterwards. LD analysis showed a transient increase followed by a reduction to baseline levels over the first 30 nights of treatment. The accommodative response was lower than expected for all target vergences in all visits (BL: 0.61 D at 1.00 D to 0.96 D at 5.00 D; 60 N: 0.36 D at 1.00 D to 0.79 D at 5.00 D). On average, the accommodative lag decreases over time with OK lens wear. However, these differences were not statistically significant (p > 0.050, repeated-measures ANOVA and Friedman test). This shows that overnight OK treatment does not affect objectively measured the accommodative response of young, low myopic eyes after two months of treatment stabilization.

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Association between cognitive phenotype in unaffected siblings and prospective 3- and 6-year clinical outcome in their proband affected by psychosis

Psychological Medicine ◽

10.1017/s0033291720000719 ◽

2020 ◽

pp. 1-11

Author(s):

Thijs J. Burger ◽

Frederike Schirmbeck ◽

Jentien M. Vermeulen ◽

Piotr J. Quee ◽

Mariken B. de Koning ◽

...

Keyword(s):

Repeated Measures ◽

Psychotic Disorders ◽

Cognitive Vulnerability ◽

Familial Risk ◽

Related Factors ◽

Cross Sectional ◽

The Impact ◽

Cognitive Alterations ◽

Over Time

Abstract Background Cognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients. Methods In total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes (‘normal’, ‘mixed’ and ‘impaired’) in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype. Results Probands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype. Conclusions Cross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.

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Maternal Gut Microbiome Biodiversity in Pregnancy

American Journal of Perinatology ◽

10.1055/s-0037-1604412 ◽

2017 ◽

Vol 35 (01) ◽

pp. 024-030 ◽

Cited By ~ 16

Author(s):

Nitasha Ricks ◽

Alexis Panzer ◽

Amber Mccoy ◽

M. Azcarate-Peril ◽

Temitope Keku ◽

...

Keyword(s):

Gut Microbiome ◽

High Throughput Sequencing ◽

White Women ◽

Phase 1 ◽

Rrna Gene ◽

Fecal Samples ◽

Gestational Weight ◽

Biodiversity Changes ◽

In Pregnancy

Objective To measure maternal gut microbiome biodiversity in pregnancy. Materials and Methods In phase 1, maternal fecal samples were collected by rectal swab in 20 healthy pregnant women (14–28 weeks gestation) to measure bacterial abundance. In phase 2, fecal samples were collected from 31 women at enrollment (<20 weeks gestation, baseline) and at 36 to 39 weeks of gestation (follow-up). We assessed cluster analysis to assess bacterial community profiles at the phylum level longitudinally through pregnancy. DNA was extracted from swabs, followed by PCR of the bacterial 16s rRNA gene and multiplex high-throughput sequencing (Ion Torrent). Results In phase 1, 16 of 20 samples yielded usable data. White women (n = 10) had greater abundance of Firmicutes (23 ± 0.15 vs. 16% ± 0.75, p = 0.007) and Bacteroidetes (24 ± 0.14 vs. 19% ± 0.68, p = 0.015) compared with non-White women (n = 6). In the 11 paired specimens, Bacteroidetes increased in abundance from baseline to follow-up. Compared with women who gained weight below the median gestational weight gain (GWG, <15.4 kg), those who gained above the median GWG had increased abundance of Bacteroidetes (p = 0.02) and other phyla (p = 0.04). Conclusion Maternal microbiome biodiversity changes as pregnancy progresses and correlates with GWG.

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Bimonthly assessment of magnetization transfer magnetic resonance imaging parameters in multiple sclerosis: a 14-month, multicentre, follow-up study

Multiple Sclerosis Journal ◽

10.1177/1352458509358713 ◽

2010 ◽

Vol 16 (3) ◽

pp. 325-331 ◽

Cited By ~ 7

Author(s):

S. Mesaros ◽

MA Rocca ◽

MP Sormani ◽

P. Valsasina ◽

C. Markowitz ◽

...

Keyword(s):

Multiple Sclerosis ◽

Treatment Effect ◽

Repeated Measures ◽

Magnetization Transfer ◽

Random Effect ◽

Lesion Volume ◽

Sample Sizes ◽

Double Blind ◽

Over Time

This study was performed to assess the temporal evolution of damage within lesions and the normal-appearing white matter, measured using frequent magnetization transfer (MT) MRI, in relapsing—remitting multiple sclerosis (RRMS). The relationship of MT ratio (MTR) changes with measures of lesion burden, and the sample sizes needed to demonstrate a treatment effect on MTR metrics in placebo-controlled MS trials were also investigated. Bimonthly brain conventional and MT MRI scans were acquired from 42 patients with RRMS enrolled in the placebo arm of a 14-month, double-blind trial. Longitudinal MRI changes were evaluated using a random effect linear model accounting for repeated measures, and adjusted for centre effects. The Expanded Disability Status Scale (EDSS) score remained stable over the study period. A weak, but not statistically significant, decrease over time was detected for normal-appearing brain tissue (NABT) average MTR (—0.02% per visit; p = 0.14), and MTR peak height (—0.15 per visit; p = 0.17), while average lesion MTR showed a significant decrease over the study period (—0.07% per visit; p = 0.03). At each visit, all MTR variables were significantly correlated with T2 lesion volume (LV) (average coefficients of correlation ranging from —0.54 to —0.28, and p-values from <0.001 to 0.02). At each visit, NABT average MTR was also significantly correlated with T1-hypointense LV (average coefficient of correlation = —0.57, p < 0.001). The estimation of the sample sizes required to demonstrate a reduction of average lesion MTR (the only parameter with a significant decrease over the follow-up) ranged from 101 to 154 patients to detect a treatment effect of 50% in a 1-year trial with a power of 90%. The steady correlation observed between conventional and MT MRI measures over time supports the hypothesis of axonal degeneration of fibres passing through focal lesions as one of the factors contributing to the overall MS burden.

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Development of white matter fibre density and morphology over childhood: a longitudinal fixel-based analysis

10.1101/342097 ◽

2018 ◽

Cited By ~ 1

Author(s):

Sila Genc ◽

Robert E Smith ◽

Charles B Malpas ◽

Vicki Anderson ◽

Jan M Nicholson ◽

...

Keyword(s):

White Matter ◽

Cross Section ◽

Repeated Measures ◽

Pubertal Stage ◽

Full Spectrum ◽

Fibre Density ◽

Fibre Development ◽

Over Time ◽

Time Point

AbstractPurposeWhite matter fibre development in childhood involves dynamic changes to microstructural organisation driven by increasing axon diameter, density, and myelination. However, there is a lack of longitudinal studies that have quantified advanced diffusion metrics to identify regions of accelerated fibre maturation, particularly across the early pubertal period. We applied a novel longitudinal fixel-based analysis (FBA) framework, in order to estimate microscopic and macroscopic white matter changes over time.MethodsDiffusion-weighted imaging (DWI) data were acquired for 59 typically developing children (27 female) aged 9 – 13 years at two time-points approximately 16 months apart (time-point 1: 10.4 ± 0.4 years, time-point 2: 11.7 ± 0.5 years). Whole brain FBA was performed using the connectivity-based fixel enhancement method, to assess longitudinal changes in fibre microscopic density and macroscopic morphological measures, and how these changes are affected by sex, pubertal stage, and pubertal progression. Follow-up analyses were performed in sub-regions of the corpus callosum to confirm the main findings using a Bayesian repeated measures approach.ResultsThere was a statistically significant increase in fibre density over time localised to medial and posterior commissural and association fibres, including the forceps major and bilateral superior longitudinal fasciculus. Increases in fibre cross-section were substantially more widespread. The rate of fibre development was not associated with age or sex. In addition, there was no significant relationship between pubertal stage or progression and longitudinal fibre development over time. Follow-up Bayesian analyses were performed to confirm the findings, which supported the null effect of the longitudinal pubertal comparison.ConclusionUsing a novel longitudinal fixel-based analysis framework, we demonstrate that white matter fibre density and fibre cross-section increased within a 16-month scan rescan period in specific regions. The observed increases might reflect increasing axonal diameter or axon count. Pubertal stage or progression did not influence the rate of fibre development in the early stages of puberty. Future work should focus on quantifying these measures across a wider age range to capture the full spectrum of fibre development across the pubertal period.

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Using Prophylactic Prolene Mesh to Reduce the Incidence of Incisional Hernia at the Site of Stoma Closure

QJM ◽

10.1093/qjmed/hcab097.047 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Hassan Sayed Tantawy ◽

Mohamed Mahfouz Mohamed ◽

Ahmed Yasser Abdel Halim ◽

Mostafa Mohamed Abdel Aziz

Keyword(s):

Incisional Hernia ◽

Prospective Study ◽

Clinical Examination ◽

Stoma Closure ◽

Prolene Mesh ◽

Incisional Hernias ◽

Stoma Site ◽

A Prospective Study ◽

Over Time

Abstract Background Incisional hernias at stoma sites are not an infrequent problem, occurring in up to 30% of cases and it also varied in a range of studies from 0-48%. Objectives This is a prospective study to detect the feasibility of application of prolene mesh at the site of stoma closure in reducing the rate of post stomal incisional. INTRODUCTION Abdominal wall hernias are common and are a significant cause of morbidity. Stomas are commonly constructed following colorectal surgery to protect distal anastomosis or when sepsis prevents primary anastomosis. There is a risk of a wide range of morbidity following both stoma formation and stoma reversal (Chow et al., 2009). Incisional hernias at stoma sites are not an infrequent problem, occurring in up to 30% of cases and it also varied in a range of studies from 0-48% (Tilney et al., 2008). They occur over time and are generally under-reported, which may be due to the elderly nature of the population, the significant co-morbidities or early discharge from follow-up (Cingi et al., 2006). One in three patients may develop a hernia after stoma closure, and around half of hernias that are detected require repair.Risk of hernia is greater after colostomy closure than after ileostomy closure(Bhangu et al., 2012). A meta-analysis published in 2012 investigated the incidence of incisional hernia following closure of stoma, The overall mean incisional hernia rate following stoma closures was 7.4%. The authors reported a lower risk of hernia following reversal of ileostomy when compared to respectively (Bhangu et al., 2012). A further systematic review found a similar incidence for stoma site incisional hernias to be 8.3% (0–33.9%) (Nguyen et al., 2014). Two factors should be noted with regard to the incidence of stoma site hernia. Firstly, that the long-term risk is not known and secondly, that clinical examination alone is shown to have a lower detection rate of incisional hernia post stoma closure when compared to clinical imaging (Bhangu et al., 2012; Cingi et al., 2006). Therefore, studies focusing on only clinical examination may be underestimating the prevalence, as radiological detected herniae may become symptomatic over time and may be missed in studies with a short follow-up period. AIM OF THE WORK This is a prospective study to detect the feasibility of application of prolene mesh at the site of stoma closure in reducing the rate of post stomal incisional.

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Abstract 14231: Effectiveness and Safety of Statin Therapy in Children: A Multi-Center, Real-World Clinical Practice Experience

Circulation ◽

10.1161/circ.132.suppl_3.14231 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Rae Ellen W Kavey ◽

Cedric Manlhiot ◽

Tanveer Collins ◽

Samuel S Gidding ◽

Matthew Demczko ◽

...

Keyword(s):

Clinical Practice ◽

Statin Therapy ◽

Real World ◽

Repeated Measures ◽

Lifestyle Modification ◽

Safety Data ◽

Primary Hypercholesterolemia ◽

Mean Compliance ◽

Over Time

Results of statin use in clinical practice in children are very limited, with effectiveness and safety data based on short-term clinical trials. To address this, we reviewed the results of all children with primary hypercholesterolemia treated with statins for more than 6 months from 4 Pediatric Lipid Clinics. Expert Panel guidelines recommend statin if LDL-cholesterol (LDL-C) exceeds 4.9 mmol/L (190 mg/dL), or 4.1 mmol/L (160 mg/dL) with additional risk factors, after 6 months of lifestyle modification, with hepatic enzyme monitoring plus clinical surveillance and CK measurement for myositis. Patients at all study sites were managed using these guidelines. Results: There were 246 pts (59% male) who had 1488 clinical assessments. Mean age at statin initiation was 12.5±0.5 yrs. Mean duration of therapy was 2.9 yrs (IQR: 1.9_4.7) with 48% more than 3 yrs. Initial statin prescribed varied over time but 61% of pts were started on atorvastatin and 70% remained on the first statin prescribed. Mean compliance was assessed at 92% and 234 pts (94%) remained on statin therapy at the end of the review. Baseline and follow-up lab values and anthropometry (mean + SD) appear below. While 13 pts (5%) had transient AST or ALT > 3xULN, or CK >10xULN at some time during follow-up, no pt was diagnosed with myositis. In regression analysis adjusted for repeated measures over time, statin treatment was associated with significant reductions in total cholesterol, LDL-C and non-HDL-C with no change in HDL-C, TG, safety labs or anthropometry. Despite statin, 51% and 70% of pts had LDL-C levels above minimal (<3.35mmol/L; 130 mg/dL) and ideal (<2.85mmol/L; 110 mg/dL) targets at last follow-up. Conclusions: These findings in a large series of pts from real-world clinical practice show that statin therapy in children with primary hypercholesterolemia is safe and effectively lowers LDL-C on mid-term follow-up. Side effects are rare and discontinuation of treatment is uncommon.

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Organophosphate and carbamate insecticide exposure is related to lung function change among smallholder farmers: a prospective study

Thorax ◽

10.1136/thoraxjnl-2020-214609 ◽

2021 ◽

pp. thoraxjnl-2020-214609

Author(s):

Martin Rune Hassan Hansen ◽

Erik Jørs ◽

Annelli Sandbæk ◽

Daniel Sekabojja ◽

John C Ssempebwa ◽

...

Keyword(s):

Lung Function ◽

Prospective Study ◽

Family Relationships ◽

Repeated Measures ◽

Smallholder Farmers ◽

Z Score ◽

Carbamate Insecticides ◽

Z Scores ◽

A Prospective Study

Introduction and aimExposure to some insecticides may cause airway obstruction, but existing evidence is limited by cross-sectional designs and inadequate confounder control. We investigated the relation between organophosphate and carbamate insecticides and pulmonary function in a prospective study accounting for important confounders.MethodsIn a cohort of 364 smallholder farmers in Uganda (69% women), participants underwent pre-bronchodilator spirometry at baseline (September/October 2018) and at two follow-up visits (November/December 2018 and January/February 2019). Exposure to carbamate and organophosphate insecticides was assessed using haemoglobin-adjusted erythrocyte acetylcholinesterase (AChE/Hb). Less than 3% of participants were lost to follow-up. We calculated Z-scores for FEV1, FVC and FEV1/FVC using the Global Lung Function Initiative equations. Data were analysed in linear mixed and fixed effect models accounting for family relationships and repeated measures of exposure and outcome.ResultsLow AChE/Hb was significantly associated with low FEV1 Z-score in both unadjusted and adjusted analyses. Compared with individuals with AChE/Hb 25.90 U/g (50th percentile, reference), those with lower AChE/Hb 24.50 U/g (35th percentile) had mean FEV1 Z-score 0.045 (0.003 to 0.087) lower, and persons with higher AChE/Hb 27.30 U/g (65th percentile) had a mean FEV1 Z-score 0.043 (−0.002 to 0.087) higher compared with the reference. Similar, but numerically smaller and statistically non-significant effects were seen for Z-scores of FVC and FEV1/FVC.ConclusionExposure to organophosphate and carbamate insecticides may lead to lung function decline. Our results add to the growing evidence of health effects in relation to exposure to organophosphate and carbamate insecticides, underlining the importance of minimising exposure.

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