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Cytoreductive prostatectomy may improve oncological outcomes in patients with oligometastatic prostate cancer: An updated systematic review and meta-analysis

Investig Clin Urol. 2023 May;64(3):242-254. doi: 10.4111/icu.20230058.

ABSTRACT

The oncologic outcomes of cytoreductive prostatectomy (CRP) in oligometastatic prostate cancer (OmPCa) are still controversial. Therefore, we conducted a systematic review and meta-analysis on the oncologic outcome of CRP in OmPCa. OVID-Medline, OVID-Embase, and Cochrane Library databases were searched to identify eligible studies published before January 2023. A total of 11 studies (929 patients), 1 randomized controlled trial (RCT) and 10 non-RCT studies, were included in the final analysis. RCT and non-RCT were further analyzed separately. End points were progression-free-survival (PFS), time to castration-resistant prostate cancer (CRPCa), cancer-specific-survival (CSS) and overall-survival (OS). It was analyzed using hazard ratio (HR) and 95% confidence intervals (CIs). In PFS, in RCT, HR=0.43 (CIs=0.27-0.69) was shown statistically significant, but in non-RCTs, HR=0.50 (CIs=0.20-1.25), there was no statistical difference. And, in time to CRPCa was statistically significant in the CRP group in all analyses (RCT; HR=0.44; CIs=0.29-0.67) (non-RCTs; HR=0.64; CIs=0.47-0.88). Next, CSS was not statistically different between the two groups (HR=0.63; CIs=0.37-1.05). Finally, OS showed better results in the CRP group in all analyses (RCT; HR=0.44; CIs=0.26-0.76) (non-RCTs; HR=0.59; CIs=0.37-0.93). Patients who received CRP in OmPCa showed better oncologic outcomes compared to controls. Notably, time to CRPC and OS showed significantly improved compared with control. We recommend that experienced urologists who are capable of managing complications consider CRP as a strategy to achieve good oncological outcomes in OmPCa. However, since most of the included studies are non-RCT studies, caution should be exercised in interpreting the results.

PMID:37341004 | DOI:10.4111/icu.20230058

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Chemical Analysis and in vitro Antiviral Effects of Northeast Türkiye Propolis Samples Against HSV-1

Chem Biodivers. 2023 Jun 21:e202300669. doi: 10.1002/cbdv.202300669. Online ahead of print.

ABSTRACT

Propolis is one of the mixtures with the widest biological activity among natural products used in complementary medicine. HSV-1 is a highly contagious and endemic virus. Available drugs are insufficient for recurrent HSV-1 infections. Therefore, new approaches to treat HSV-1 infections are still being developed. In this study, it was aimed to investigate the inhibition effect of ethanolic Anatolian propolis extracts obtained from the Eastern Black Sea Region (Pazar, Ardahan, and Uzungöl) on HSV-1. In addition to the total phenolic (TPC) and the total flavonoid content (TFC), the phenolic profiles of the extracts were analyzed by HPLC-UV. The antiviral activity of the extracts were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), quantitative Real Time Polymerase Chain Reaction (qRT-PCR), and plaque reduction tests, and the results were evaluated statistically. It was determined that the total amount of phenolic substances varied between 44.12 and 166.91 mg GAE/g, and the total flavonoid content of the samples varied between 12.50 and 41.58 (mgQUE/g). It was shown that all propolis samples used in the current study were effective against HSV-1, but the higher phenolic compounds contained in the samples showed the higher activity. The results show that ethanolic propolis extracts are promising candidates for HSV-1 treatment.

PMID:37340993 | DOI:10.1002/cbdv.202300669

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Expression analysis of MMP14: Key enzyme action in modulating visceral adipose tissue plasticity in patients with obesity

Clin Obes. 2023 Jun 21:e12607. doi: 10.1111/cob.12607. Online ahead of print.

ABSTRACT

Compromised adipose tissue plasticity is a hallmark finding of obesity orchestrated by the intricate interplay between various extracellular matrix components. Collagen6 (COL6) is well characterized in obese visceral adipose tissue (VAT), not much is known about MMP14 which is hypothesized to be the key player in matrix reorganization. Subjects with obesity (BMI ≥40; n = 50) aged 18-60 years undergoing bariatric surgery and their age-matched controls (BMI < 25; n = 30) were included. MMP14, Col6A3 and Tissue inhibitor of metalloproteinase 2 (TIMP2) mRNA expression was assessed in VAT and their serum levels along with endotrophin were estimated in both groups preoperatively and post-operatively in the obese group. The results were analysed statistically and correlated with anthropometric and glycaemic parameters, namely fasting glucose and insulin, HbA1c, HOMA-IR, HOMA-β and QUICKI. Circulating levels as well as mRNA expression profiling revealed significant differences between the individuals with and without obesity (p < .05), more so in individuals with diabetes and obesity (p < .05). Follow-up serum analysis revealed significantly raised MMP14 (p < .001), with decreased Col6A3, endotrophin and TIMP2 levels (p < .01, p < .001 and p < .01, respectively). A rise in serum MMP14 protein, simultaneous with post-surgical weight loss and decreased serum levels of associated extracellular matrix (ECM) remodellers, suggests its crucial role in modulating obesity-associated ECM fibrosis and pliability of VAT.

PMID:37340990 | DOI:10.1111/cob.12607

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Urine transfer devices may impact urinary particle results: a pre-analytical study

Clin Chem Lab Med. 2023 Jun 22. doi: 10.1515/cclm-2023-0327. Online ahead of print.

ABSTRACT

OBJECTIVES: Well-standardized procedures in the pre-analytical phase of urine diagnostics is of utmost importance to obtain reliable results. We investigated the effect of different urine collection methods and the associated urine transfer tubes on urine test strip and particle results.

METHODS: In total, 146 selected urine samples were subdivided into three different collection containers and subsequently transferred into its accompanying transfer tube (BD, Greiner, Sarstedt vacuum and Sarstedt aspiration). As reference, the original urine sample was directly measured on the analyser. Both chemical test strip analysis (Sysmex UC-3500) and fluorescence flow cytometry particle analysis (Sysmex UF-5000) were performed on all samples.

RESULTS: No statistically significant differences in test strip results were found between the studied transfer methods. On the contrary, transfer of urine samples to the secondary tubes affected their particle counts. Clinically significant reductions in counts of renal tubular epithelial cells and hyaline casts were observed using the BD and Greiner transfer tubes and in counts of pathological casts using the BD, Greiner and Sarstedt vacuum tubes.

CONCLUSIONS: The results of this study indicate that the use of urine transfer tubes may impact counts of fragile urine particles. Clinical laboratories need to be aware about the variation that urine collection methods can induce on urine particle counts.

PMID:37340894 | DOI:10.1515/cclm-2023-0327

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Permutation-based multiple testing corrections for P $$ P $$ -values and confidence intervals for cluster randomized trials

Stat Med. 2023 Jun 21. doi: 10.1002/sim.9831. Online ahead of print.

ABSTRACT

In this article, we derive and compare methods to derive P-values and sets of confidence intervals with strong control of the family-wise error rates and coverage for estimates of treatment effects in cluster randomized trials with multiple outcomes. There are few methods for P-value corrections and deriving confidence intervals, limiting their application in this setting. We discuss the methods of Bonferroni, Holm, and Romano and Wolf and adapt them to cluster randomized trial inference using permutation-based methods with different test statistics. We develop a novel search procedure for confidence set limits using permutation tests to produce a set of confidence intervals under each method of correction. We conduct a simulation-based study to compare family-wise error rates, coverage of confidence sets, and the efficiency of each procedure in comparison to no correction using both model-based standard errors and permutation tests. We show that the Romano-Wolf type procedure has nominal error rates and coverage under non-independent correlation structures and is more efficient than the other methods in a simulation-based study. We also compare results from the analysis of a real-world trial.

PMID:37340888 | DOI:10.1002/sim.9831

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Adaptations in athletic performance and muscle architecture are not meaningfully conditioned by training free-weight versus machine-based exercises: Challenging a traditional assumption using the velocity-based method

Scand J Med Sci Sports. 2023 Jun 21. doi: 10.1111/sms.14433. Online ahead of print.

ABSTRACT

BACKGROUND: Although the superior effectiveness of free-weight over machine-based training has been a traditionally widespread assumption, longitudinal studies comparing these training modalities were scarce and heterogeneous.

OBJECTIVE: This research used the velocity-based method to compare the effects of free-weight and machine-based resistance training on athletic performance and muscle architecture.

METHODS: Thirty-four resistance-trained men participated in an 8-week resistance training program allocated into free-weight (n = 17) or machine-based (n = 17) groups. Training variables (intensity, intraset fatigue, and recovery) were identical for both groups, so they only differed in the use of a barbell or specific machines to execute the full squat, bench press, prone bench pull, and shoulder press exercises. The velocity-based method was implemented to accurately adjust the planned intensity. Analysis of covariance and effect size (ES) statistics were used to compare both training modalities on a comprehensive set of athletic and muscle architecture parameters.

RESULTS: No between-group differences were found for any athletic (p ≥ 0.146) and muscle architecture (p ≥ 0.184) variable. Both training modalities significantly and similarly improved vertical jump (Free-weight: ES ≥ 0.45, p ≤ 0.001; Machine-based: ES ≥ 0.41, p ≤ 0.001) and lower limb anaerobic capacity (Free-weight: ES ≥ 0.39, p ≤ 0.007; Machine-based: ES ≥ 0.31, p ≤ 0.003). Additionally, the machine-based group meaningfully enhanced upper limb anaerobic power (ES = 0.41, p = 0.021), whereas the free-weight group significantly improved the change of direction (ES = -0.54, p = 0.003) and 2/6 balance conditions analyzed (p ≤ 0.012). Changes in sprint capacity (ES ≥ -0.13, p ≥ 0.274), fascicle length, and pennation angle (ES ≤ 0.19, p ≥ 0.129) were not significant for either training modality.

CONCLUSION: Adaptations in athletic performance and muscle architecture would not be meaningfully influenced by the resistance modality trained.

PMID:37340878 | DOI:10.1111/sms.14433

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Methylome, transcriptome and phenotype changes induced by temperature conditions experienced during sexual reproduction in Fragaria vesca

Physiol Plant. 2023 Jun 21:e13963. doi: 10.1111/ppl.13963. Online ahead of print.

ABSTRACT

Temperature conditions experienced during embryogenesis and seed development may induce epigenetic changes that increase phenotypic variation in plants. Here we investigate if embryogenesis and seed development at two different temperatures (28 vs 18°C) results in lasting phenotypic effects and DNA methylation changes in woodland strawberry (Fragaria vesca). Using five European ecotypes from Spain (ES12), Iceland (ICE2), Italy (IT4), and Norway (NOR2 and NOR29), we found statistically significant differences between plants from seeds produced at 18 or 28°C in three of four phenotypic features investigated under common garden conditions. This indicates the establishment of a temperature-induced epigenetic memory-like response during embryogenesis and seed development. The memory effect was significant in two ecotypes: in NOR2 flowering time, number of growth points and petiole length were affected, and in ES12 number of growth points was affected. This indicates that genetic differences between ecotypes in their epigenetic machinery, or other allelic differences, impact this type of plasticity. We observed statistically significant differences between ecotypes in DNA methylation marks in repetitive elements, pseudogenes and genic elements. Leaf transcriptomes were also affected by embryonic temperature in an ecotype-specific manner. Although we observed significant and lasting phenotypic change in at least some ecotypes, there was considerable variation in DNA methylation between individual plants within each temperature treatment. This within-treatment variability in DNA methylation marks in F. vesca progeny may partly be a result of allelic redistribution from recombination during meiosis and subsequent epigenetic reprogramming during embryogenesis. This article is protected by copyright. All rights reserved.

PMID:37340851 | DOI:10.1111/ppl.13963

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Lack of compensation for COVID-19-related overtime work and its association with burnout among EMS providers in South Korea

Epidemiol Health. 2023 Jun 15:e2023058. doi: 10.4178/epih.e2023058. Online ahead of print.

ABSTRACT

OBJECTIVES: This study examined the association between lack of compensation for COVID-19-related overtime work (LCCOW) and burnout among emergency medical service (EMS) providers in Seoul, South Korea.

METHODS: We conducted a cross-sectional survey of 693 EMS providers in Seoul, Korea. Participants were classified into 3 groups according to their experience of COVID-19-related overtime work and LCCOW: (i) “did not experience,” (ii) “experienced, was compensated,” and (iii) “experienced, was not compensated.” Burnout was measured using the Korean version of the Copenhagen Burnout Inventory, which has 3 subdomains: personal burnout (PB), work-related burnout (WRB), and citizen-related burnout (CRB). Multiple linear regression was applied to examine whether LCCOW was associated with burnout after adjusting for potential confounders.

RESULTS: In total, 74.2% of participants experienced COVID-19-related overtime work, and 14.6% of those who worked overtime experienced LCCOW. COVID-19-related overtime work showed a statistically non-significant association with burnout. However, the association differed by LCCOW. Compared to the “did not experience” group, the “experienced, was not compensated” group was associated with PB (β=10.519; 95% CI, 3.455‒17.584), WRB (β=10.339; 95% CI, 3.398‒17.280), and CRB (β=12.290; 95% CI, 6.900‒17.680), whereas no association was observed for the “experienced, was compensated” group. Furthermore, an analysis restricted to EMS providers who worked overtime due to COVID-19 showed that LCCOW was associated with PB (β=7.970; 95% CI, 1.064‒14.876), WRB (β=7.276; 95% CI, 0.270‒14.283), and CRB (β=10.000; 95% CI, 3.435‒16.565).

CONCLUSION: This study suggests that LCCOW could be critical in worsening burnout among EMS providers who worked overtime due to COVID-19.

PMID:37340845 | DOI:10.4178/epih.e2023058

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HPV vaccine knowledge, attitudes, and practices among New York State medical providers, dentists, and pharmacists

Hum Vaccin Immunother. 2023 Aug 1;19(2):2219185. doi: 10.1080/21645515.2023.2219185.

ABSTRACT

Healthcare provider vaccine knowledge and attitudes influence delivery of a strong vaccine recommendation. We aim to describe HPV vaccine knowledge, attitudes, and recommendation or discussion practices (KAP) among New York State medical providers, dentists, and pharmacists. A survey to assess providers’ KAP was distributed electronically to NYS members of medical organizations. Descriptive and inferential statistical methods were used to characterize provider KAP. Responses from 1637 surveys were included, from 864 (53%) medical providers, 737 (45%) dentists, and 36 (2%) pharmacists. 59% (509/864) of medical providers responded that they recommend HPV vaccine to patients, with 390/509 (77%) strongly recommending vaccine at 11-12 years. Medical providers were more likely to report recommending HPV vaccine for children ages 11-12 years if they strongly agreed that HPV vaccine prevents cancer 326/391 (83%) vs 64/117 (55%) and responded that HPV vaccination does not increase the risk of unprotected sex (386/494 (78%) vs 4/15 (25%)) (p < .05). Less than 1/3 of dentists reported discussing HPV vaccine with 11-26-year-old females (230/737, 31%) and males (205/737, 28%) at least “sometimes.” Dentists were more likely to answer that they routinely discuss HPV vaccine with children ages 11-12 years if they responded that HPV vaccination does not increase sexual activity (70/73 (96%) vs 528/662 (80%), p < .001). Few pharmacists reported discussing HPV vaccine with 11-26-year-old females (6/36 (17%)) and males (5/36 (14%)) at least “sometimes.” Gaps in HPV vaccine knowledge among providers still exist and may influence vaccine attitudes and recommendation or discussion practices.

PMID:37340826 | DOI:10.1080/21645515.2023.2219185

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Differential treatment effect between younger and older adults for new cancer therapies in solid tumors supporting US Food and Drug Administration approval between 2010 and 2021

Cancer. 2023 Jun 20. doi: 10.1002/cncr.34911. Online ahead of print.

ABSTRACT

BACKGROUND: Over one half of cancer diagnoses occur in patients aged 65 and older. The authors quantified how treatment effects differ between older and younger patients in oncology registration trials.

METHODS: The authors performed a retrospective cohort study of registration trials supporting US Food and Drug Administration approval of cancer drugs (from January 2010 to December 2021). The primary outcome was differential treatment effect by age (younger than 65 years vs. 65 years or older) for progression-free survival and overall survival. Random effects meta-analysis and a pairwise comparison of outcomes by age group also were performed.

RESULTS: Among 263 trials that met the inclusion criteria, 120 trials with 153 end points and 83,152 patients presented age-specific outcome data. Among the included randomized patients, 38% were aged 65 years and older compared with an incidence proportion of 55% in data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program. Studies evaluating prostate cancer had the highest representation of patients aged 65 years or older (73%), whereas breast cancer studies had the lowest (20%). There were no changes in the proportion of patients aged 65 years or older over time (p = .86). Only 7% of end points showed a statistically significant interaction between outcome and age group. In a pooled analysis, there was an association between treatment effect and age for progression-free survival that approached but did not meet significance (hazard ratio, 0.95; p = .06), and there was no difference for overall survival (hazard ratio, 0.97; p = .79).

CONCLUSIONS: Older adults remain under-represented in oncology registration trials. Significant differences in outcomes by age group were uncommon in individual trials and pooled analyses. However, clinical trial participants differ from real-world patients older than 65 years, and increased enrollment and ongoing research into differential treatment effects by age are needed.

PMID:37340792 | DOI:10.1002/cncr.34911