Author: Nevin Manimala

BMJ Open. 2021 Nov 30;11(11):e043242. doi: 10.1136/bmjopen-2020-043242.

ABSTRACT

OBJECTIVE: Typically, migraine prevention trials focus on reducing migraine days. This narrow focus may not capture all that is important to people with migraine. Inconsistency in outcome selection across trials limits the potential for data pooling and evidence synthesis. In response, we describe the development of core outcome set for migraine (COSMIG).

DESIGN: A two-stage approach sought to achieve international, multistakeholder consensus on both the core domain set and core measurement set. Following construction of a comprehensive list of outcomes, expert panellists (patients, healthcare professionals and researchers) completed a three-round electronic-Delphi study to support a reduction and prioritisation of core domains and outcomes. Participants in a consensus meeting finalised the core domains and methods of assessment. All stages were overseen by an international core team, including patient research partners.

RESULTS: There was a good representation of patients (episodic migraine (n=34) and chronic migraine (n=42)) and healthcare professionals (n=33) with high response and retention rates. The initial list of domains and outcomes was reduced from >50 to 7 core domains for consideration in the consensus meeting, during which a 2-domain core outcome set was agreed.

CONCLUSION: International and multistakeholder consensus emerged to describe a two-domain core outcome set for reporting research on preventive interventions for chronic and episodic migraine: migraine-specific pain and migraine-specific quality of life. Intensity of migraine pain assessed with an 11-point Numerical Rating Scale and the frequency as the number of headache/migraine days over a specified time period. Migraine-specific quality of life assessed using the Migraine Functional Impact Questionnaire.

PMID:34848505 | DOI:10.1136/bmjopen-2020-043242

Anticancer Res. 2021 Dec;41(12):6287-6292. doi: 10.21873/anticanres.15450.

ABSTRACT

BACKGROUND/AIM: To retrospectively analyze the results of histoculture drug response assays (HDRAs) to determine whether the results could predict platinum sensitivity and prognosis in ovarian cancer.

PATIENTS AND METHODS: One hundred thirty-nine patients with ovarian cancer were reviewed. HDRAs were conducted for platinum and taxane agents. Platinum resistance and sensitivity occurred in 21 and 118 patients, respectively. To analyze the relationship between the inhibition rates (IRs) of tumor growth caused by the platinum agent and clinical outcomes, Student’s t-test and linear regression analysis were used.

RESULTS: We found that the average IRs of the platinum and taxane agent were not statistically significant between the platinum-sensitive and – resistant groups. There was no statistical significance for overall survival, progression-free survival, or platinum-free interval.

CONCLUSION: The HDRA is not useful for predicting platinum sensitivity and survival outcomes.

PMID:34848485 | DOI:10.21873/anticanres.15450

Anticancer Res. 2021 Dec;41(12):6267-6272. doi: 10.21873/anticanres.15447.

ABSTRACT

BACKGROUND/AIM: Treatments containing ipilimumab have shown a good outcome in patients with non-small cell lung cancer (NSCLC) regardless of the PD-L1 tumor proportion score (TPS). However, the association between PD-L1 TPS and the expression of CTLA-4 in tumor-infiltrating lymphocytes is unknown.

PATIENTS AND METHODS: Fifty-five NSCLC patients who underwent surgery in our hospital were included in this study. We measured the proportions of CTLA-4⁺ regulatory T cells, and CTLA-4⁺ CD8 T cells, and statistically analyzed their correlations with the PD-L1 TPS.

RESULTS: Statistical correlations were found neither between the proportion of CTLA-4⁺ regulatory T cells to CD8 T cells and the PD-L1 TPS (p=0.2859) nor between the proportion of CTLA-4⁺ cells in CD8 T cells and the PD-L1 TPS (p=0.1919).

CONCLUSION: The proportions of CTLA-4⁺ regulatory T cells to CD8 T cells and CTLA-4⁺ cells in CD8 T cells were irrelevant to the PD-L1 TPS in NSCLC patients.

PMID:34848482 | DOI:10.21873/anticanres.15447

Anticancer Res. 2021 Dec;41(12):5959-5971. doi: 10.21873/anticanres.15415.

ABSTRACT

BACKGROUND/AIM: We examined the inhibitory effects of both glyoxalase 1 (GLO 1) and protein kinase C (PKC)λ in aldehyde dehydrogenase 1 (ALDH1)-positive breast cancer stem cells (CSCs).

MATERIALS AND METHODS: Breast cancer genomics datasets (TCGA, n=593; METABRIC, n=1904) were downloaded and statistically analyzed. The effects of GLO 1 and PKCλ on trypan blue staining and tumor-sphere formation by ALDH1^high cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined.

RESULTS: GLO 1^high, PKCλ^high, and ALDH1A3^high tumors were enriched in stage I/II/III/IV samples, associated with the HER2 and TNBC subtypes according to receptor status, and associated with the HER2-enriched and basal-like subtypes according to PAM50. Inhibition of either GLO 1 (TLSC702) or PKCλ (ANF) suppressed tumor-sphere formation and enhanced death in ALDH1^high cells. TLSC702 also effectively inhibited tumor-sphere formation and induced death in PKCλ knockout ALDH1^high cells.

CONCLUSION: GLO 1 and PKCλ are important for the survival of ALDH1-positive breast CSCs, and may represent potential therapeutic targets for the treatment of ALDH1-positive breast CSCs.

PMID:34848450 | DOI:10.21873/anticanres.15415

J Allergy Clin Immunol Pract. 2021 Nov 27:S2213-2198(21)01295-2. doi: 10.1016/j.jaip.2021.11.017. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-μg peanut protein (Viaskin™ Peanut 250 μg [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children.

OBJECTIVE: To examine the safety of VP250 in children, using a study design approximating potential real-world use.

METHODS: REALISE is a phase 3 multicenter study consisting of a 6-month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported.

RESULTS: Three hundred ninety-three children were randomized 3:1 to receive VP250 (n=294) or placebo (n=99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued due to adverse events. Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall adverse event rates were similar among participants with and without history of peanut anaphylaxis.

CONCLUSIONS: In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.

PMID:34848381 | DOI:10.1016/j.jaip.2021.11.017

J Obstet Gynaecol Can. 2021 Nov 27:S1701-2163(21)00835-5. doi: 10.1016/j.jogc.2021.11.009. Online ahead of print.

ABSTRACT

A quality assurance study was completed following the implementation of a standardized opioid prescribing and education protocol post cesarean delivery. The primary goal was to determine the need for a policy on postpartum opioid prescribing practices and whether the protocol worked. There was a decrease in the number of tablets provided post intervention and no statistically significant maternal or neonatal readmissions for suspected opioid toxicity or pain control. Combination prescribing of Tylenol 3 and/or tramadol and another opioid occurred in both groups. Our results show a need for concise guidelines regarding opioid prescribing following cesarean delivery.

PMID:34848352 | DOI:10.1016/j.jogc.2021.11.009

Neuroimage. 2021 Nov 27:118751. doi: 10.1016/j.neuroimage.2021.118751. Online ahead of print.

ABSTRACT

BACKGROUND: Large-scale longitudinal and multi-centre studies are used to explore neuroimaging markers of normal aging, and neurodegenerative and mental health disorders. Longitudinal changes in brain structure are typically small, therefore the reliability of automated techniques is crucial. Determining the effects of different factors on reliability allows investigators to control those adversely affecting reliability, calculate statistical power, or even avoid particular brain measures with low reliability. This study examined the impact of several image acquisition and processing factors and documented the test-retest reliability of structural MRI measurements.

METHODS: In Phase I, 20 healthy adults (11 females; aged 20-30 years) were scanned on two occasions three weeks apart on the same scanner using the ADNI-3 protocol. On each occasion, individuals were scanned twice (repetition), after re-entering the scanner (reposition) and after tilting their head forward. At one year follow-up, nine returning individuals and 11 new volunteers were recruited for Phase II (11 females; aged 22-31 years). Scans were acquired on two different scanners using the ADNI-2 and ADNI-3 protocols. Structural images were processed using FreeSurfer (v5.3.0, 6.0.0 and 7.1.0) to provide subcortical and cortical volume, cortical surface area and thickness measurements. Intra-class correlation coefficients (ICC) were calculated to estimate test-retest reliability. We examined the effect of repetition, reposition, head tilt, time between scans, MRI sequence and scanner on reliability of structural brain measurements. Mean percentage differences were also calculated in supplementary analyses.

RESULTS: Using the FreeSurfer v7.1.0 longitudinal pipeline, we observed high reliability for subcortical and cortical volumes, and cortical surface areas at repetition, reposition, three weeks and one year (mean ICCs>0.97). Cortical thickness reliability was lower (mean ICCs>0.82). Head tilt had the greatest adverse impact on ICC estimates, for example reducing mean right cortical thickness to ICC=0.74. In contrast, changes in ADNI sequence or MRI scanner had a minimal effect. We observed an increase in reliability for updated FreeSurfer versions, with the longitudinal pipeline consistently having a higher reliability than the cross-sectional pipeline.

DISCUSSION: Longitudinal studies should monitor or control head tilt to maximise reliability. We provided the ICC estimates and mean percentage differences for all FreeSurfer brain regions, which may inform power analyses for clinical studies and have implications for the design of future longitudinal studies.

PMID:34848299 | DOI:10.1016/j.neuroimage.2021.118751

Urology. 2021 Nov 27:S0090-4295(21)01092-X. doi: 10.1016/j.urology.2021.11.019. Online ahead of print.

ABSTRACT

OBJECTIVE: To define risk factors and perioperative outcomes for matrix stones and compare these outcomes with struvite and calcium stone cohorts.

METHODS: A retrospective cohort study comparing matrix stones (n=32), struvite stones (n=23) and a matched, calcium stone control group (n=32) was performed. Two-way ANOVA was used to compare the groups for continuous variables. Chi-square tests were used to compare categorical variables. Significance was set at p<0.05. All statistical tests were performed using R (v1.73).

RESULTS: We identified no differences in age, gender, or BMI between the three groups. Matrix and struvite stones were more likely to have a history of prior stone surgery and recurrent UTIs compared to calcium stones (p=0.027 and p<0.001, respectively). Struvite stones were more likely to present as staghorn calculi compared to matrix or calcium stones (56.5% vs 21.7% vs 18.8%, p=0.006). There were no significant differences in postoperative stone free rates (p=0.378). No significant differences in postoperative infectious complications were identified. Matrix stones were more likely to have Candida on stone culture compared to the struvite or calcium stones (p<0.0001).

CONCLUSION: Matrix and struvite stones were more likely have a history of stone surgery and preoperative recurrent UTIs. Struvite stones were more likely to present as staghorn calculi. Matrix stones were more likely to have Candida present in stone cultures. However, no difference in postoperative infectious outcomes or stone free rates were identified. Further study with larger cohorts is necessary to distinguish matrix stone postoperative outcomes from struvite and calcium stones.

PMID:34848277 | DOI:10.1016/j.urology.2021.11.019

Plant Pathol J. 2021 Oct;37(5):446-454. doi: 10.5423/PPJ.OA.04.2021.0059. Epub 2021 Oct 1.

ABSTRACT

Plant-parasitic nematodes are not only an important constraint on agricultural crop production, but also cause both direct and indirect damage to turfgrass, which is a ground cover plant. However, studies on plant-parasitic nematodes of turfgrass in Korea are scarce. A survey for plant-parasitic nematodes was carried out on 13 golf courses in Korea. The results yielded 28 species/taxa belonging to 16 genera and 12 families of plant-parasitic nematodes. Among the isolated species, Helicotylenchus microlobus, Mesocriconema nebraskense, Tylenchorhynchus claytoni, Mesocriconema sp., and Meloidogyne graminicola were the most prevalent species in all management zones. Twelve species were new records of plant-parasitic nematodes in Korea. Highest maximum densities were showed by T. claytoni, Paratylenchus nanus, M. nebraskense, M. graminicola, and H. microlobus. Diversity (H’), was significantly higher in fairways compared to tees and greens, though species evenness (J’) and dominance (D) showed no statistically significant differences. This information is crucial in nematode problem diagnosis, and the subsequent formulation of management strategies.

PMID:34847631 | DOI:10.5423/PPJ.OA.04.2021.0059

Int J Urol. 2021 Nov 30. doi: 10.1111/iju.14751. Online ahead of print.

ABSTRACT

OBJECTIVES: Metastatic renal cell carcinoma can occur synchronously or metachronously. We characterized the time from diagnosis to systematic therapy as a categorical variable to analyze its effect on the overall survival and first-line treatment efficacy of metastatic renal cell carcinoma patients.

METHODS: We initially enrolled 949 consecutive metastatic renal cell carcinoma patients treated with targeted therapies retrospectively from December 2005 to December 2019. X-tile analysis was used to determine cut-off values of time from diagnosis to systematic therapy referring to overall survival. Patients were divided into different groups based on the time from diagnosis to systematic therapy and then analyzed for survival.

RESULTS: Of 358 eligible patients with metastatic renal cell carcinoma, 125 (34.9%) had synchronous metastases followed by cytoreductive nephrectomy, and 233 (65.1%) had metachronous metastases. A total of 28 patients received complete metastasectomy. Three optimal cut-off values for the time from diagnosis to systematic therapy (months) – 1.1, 7.0 and 35.9 – were applied to divide the population into four groups: the synchro group (time from diagnosis to systematic therapy ≤1.0), early group (1.0 < time from diagnosis to systematic therapy ≤ 7.0), intermediate group (7.0 < time from diagnosis to systematic therapy < 36.0) and late group (time from diagnosis to systematic therapy ≥36.0). The targeted therapy-related overall survival (P < 0.001) and progression-free survival (P < 0.001) values were significantly different among the four groups. Patients with longer time from diagnosis to systematic therapy had better prognoses and promising efficacy of targeted therapy. With the prolongation of time from diagnosis to systematic therapy, complete metastasectomy was more likely to achieve and bring a better prognosis.

CONCLUSIONS: The time from diagnosis to systematic therapy impacts the survival of metastatic renal cell carcinoma patients treated with targeted therapy. The cutoff points of 1, 7 and 36 months were statistically significant. The statistical boundaries might be valuable in future model establishment.

PMID:34847622 | DOI:10.1111/iju.14751