Nevin Manimala

Am J Clin Nutr. 2021 Mar 1:nqaa422. doi: 10.1093/ajcn/nqaa422. Online ahead of print.

ABSTRACT

BACKGROUND: B vitamins have been associated with the risk and progression of colorectal cancer (CRC), given their central roles in nucleotide synthesis and methylation, yet their association with quality of life in established CRC is unclear.

OBJECTIVES: To investigate whether quality of life 6 months postdiagnosis is associated with: 1) circulating concentrations of B vitamins and related biomarkers 6 months postdiagnosis; 2) changes in these concentrations between diagnosis and 6 months postdiagnosis; 3) B-vitamin supplement use 6 months postdiagnosis; and 4) changes in B-vitamin supplement use between diagnosis and 6 months postdiagnosis.

METHODS: We included 1676 newly diagnosed stage I-III CRC patients from 3 prospective European cohorts. Circulating concentrations of 9 biomarkers related to the B vitamins folate, riboflavin, vitamin B6, and cobalamin were measured at diagnosis and 6 months postdiagnosis. Information on dietary supplement use was collected at both time points. Health-related quality of life (global quality of life, functioning scales, and fatigue) was assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 6 months postdiagnosis. Confounder-adjusted linear regression analyses were performed, adjusted for multiple testing.

RESULTS: Higher pyridoxal 5′-phosphate (PLP) was cross-sectionally associated with better physical, role, and social functioning, as well as reduced fatigue, 6 months postdiagnosis. Associations were observed for a doubling in the hydroxykynurenine ratio [3-hydroxykynurenine: (kynurenic acid + xanthurenic acid + 3-hydroxyanthranilic acid + anthranilic acid); an inverse marker of vitamin B6] and both reduced global quality of life (β = -3.62; 95% CI: -5.88, -1.36) and worse physical functioning (β = -5.01; 95% CI: -7.09, -2.94). Dose-response relations were observed for PLP and quality of life. No associations were observed for changes in biomarker concentrations between diagnosis and 6 months. Participants who stopped using B-vitamin supplements after diagnosis reported higher fatigue than nonusers.

CONCLUSIONS: Higher vitamin B6 status was associated with better quality of life, yet limited associations were observed for the use of B-vitamin supplements. Vitamin B6 needs further study to clarify its role in relation to quality of life.

PMID:33668069 | DOI:10.1093/ajcn/nqaa422

Am J Clin Nutr. 2021 Mar 1:nqaa439. doi: 10.1093/ajcn/nqaa439. Online ahead of print.

ABSTRACT

BACKGROUND: Choline deficiency has numerous negative health consequences; although the preponderance of the US population consumes less than the recommended Adequate Intake (AI), clinical assessment of choline status is difficult. Further, several pathways involved in primary metabolism of choline are estrogen-sensitive and the AI for premenopausal women is lower than that for men.

OBJECTIVES: We sought to determine whether in vivo magnetic resonance spectroscopy (MRS) of liver and/or isotope-dilution MS of plasma could identify biomarkers reflective of choline intake (preregistered primary outcomes 1 and 2, secondary outcome 1). Determination of whether biomarker concentrations showed sex dependence was a post hoc outcome. This substudy is a component of a larger project to identify a clinically useful biomarker panel for assessment of choline status.

METHODS: In a double-blind, randomized, crossover trial, people consumed 3 diets, representative of ∼100%, ∼50%, and ∼25% of the choline AI, for 2-wk periods. We measured the concentrations of choline and several metabolites using 1H single-voxel MRS of liver in vivo and using 2H-labeled isotope dilution MS of several choline metabolites in extracted plasma.

RESULTS: Plasma concentrations of 2H9-choline, unlabeled betaine, and 2H9-betaine, and the isotopic enrichment ratio (IER) of betaine showed highly significant between-diet effects (q < 0.0001), with unlabeled betaine concentration decreasing 32% from highest to lowest choline intake. Phosphatidylcholine IER was marginally significant (q = 0.03). Unlabeled phosphatidylcholine plasma concentrations did not show between-diet effects (q = 0.34). 2H9 (trimethyl)-phosphatidylcholine plasma concentrations (q = 0.07) and MRS-measured total soluble choline species liver concentrations (q = 0.07) showed evidence of between-diet effects but this was not statistically significant.

CONCLUSIONS: Although MRS is a more direct measure of choline status, variable spectral quality limited interpretation. MS analysis of plasma showed clear correlation of plasma betaine concentration, but not plasma phosphatidylcholine concentration, with dietary choline intake. Plasma betaine concentrations also correlate with sex status (premenopausal women, postmenopausal women, men).This trial was registered at clinicaltrials.gov as NCT03726671.

PMID:33668062 | DOI:10.1093/ajcn/nqaa439

Am J Clin Nutr. 2021 Mar 1:nqaa440. doi: 10.1093/ajcn/nqaa440. Online ahead of print.

ABSTRACT

BACKGROUND: There is an emerging viewpoint that change in body weight is not sufficiently sensitive to promptly identify clinically meaningful change in body composition, such as skeletal muscle depletion.

OBJECTIVES: We aimed to determine whether body weight stability is associated with skeletal muscle depletion and whether skeletal muscle depletion is prognostic of death independently of change in body weight.

METHODS: This retrospective cohort included 1921 patients with stage I-III colorectal cancer. Computed tomography (CT)-based skeletal muscle characteristics and body weight were measured at diagnosis and after a mean 15.0-mo follow-up. Body weight stability was defined as weight change less than ±5% during follow-up. Sarcopenia and myosteatosis were defined using established thresholds for patients with cancer. Multivariable-adjusted logistic and flexible parametric proportional hazards survival models were used to quantify statistical associations.

RESULTS: At follow-up, 1026 (53.3%) patients were weight stable. Among patients with weight stability, incident sarcopenia and myosteatosis occurred in 8.5% (95% CI: 6.3%, 10.6%) and 13.5% (95% CI: 11.1%, 15.9%), respectively. Men were more likely to be weight stable than were women (56.7% compared with 49.9%; P = 0.04). Weight-stable men were less likely to develop incident sarcopenia (5.4% compared with 15.4%; P = 0.003) and myosteatosis (9.3% compared with 20.8%; P = 0.001) than weight-stable women. Among all patients, the development of incident sarcopenia (HR: 1.40; 95% CI: 1.02, 1.91) and of myosteatosis (HR: 1.41; 95% CI: 1.05, 1.90) were associated with a higher risk of death, independently of change in body weight. Patient sex did not modify the relation between skeletal muscle depletion and death.

CONCLUSIONS: Body weight stability masks clinically meaningful skeletal muscle depletion. Body composition quantified using clinically acquired CT images may provide a vital sign to identify patients at increased risk of death. These data may inform the design of future cachexia trials.

PMID:33668052 | DOI:10.1093/ajcn/nqaa440

J Neurosurg. 2021 Mar 5:1-12. doi: 10.3171/2020.7.JNS20257. Online ahead of print.

ABSTRACT

OBJECTIVE: An assessment of the transcranial approach (TCA) and the endoscopic endonasal approach (EEA) for craniopharyngiomas (CPs) according to tumor types has not been reported. The aim of this study was to evaluate both surgical approaches for different types of CPs.

METHODS: A retrospective review of primary resected CPs was performed. A QST classification system based on tumor origin was used to classify tumors into 3 types as follows: infrasellar/subdiaphragmatic CPs (Q-CPs), subarachnoidal CPs (S-CPs), and pars tuberalis CPs (T-CPs). Within each tumor type, patients were further arranged into two groups: those treated via the TCA and those treated via the EEA. Patient and tumor characteristics, surgical outcomes, and postoperative complications were obtained. All variables were statistically analyzed between surgical groups for each tumor type.

RESULTS: A total of 315 patients were included in this series, of whom 87 were identified with Q-CPs (49 treated via TCA and 38 via EEA); 56 with S-CPs (36 treated via TCA and 20 via EEA); and 172 with T-CPs (105 treated via TCA and 67 via EEA). Patient and tumor characteristics were equivalent between both surgical groups in each tumor type. The overall gross-total resection rate (90.5% TCA vs 91.2% EEA, p = 0.85) and recurrence rate (8.9% TCA vs 6.4% EEA, p = 0.35) were similar between surgical groups. The EEA group had a greater chance of visual improvement (61.6% vs 35.8%, p = 0.01) and a decreased risk of visual deterioration (1.6% vs 11.0%, p < 0.001). Of the patients with T-CPs, postoperative hypothalamic status was better in the TCA group than in the EEA group (p = 0.016). Postoperative CSF leaks and nasal complication rates occurred more frequently in the EEA group (12.0% vs 0.5%, and 9.6% vs 0.5%; both p < 0.001). For Q-CPs, EEA was associated with an increased gross-total resection rate (97.4% vs 85.7%, p = 0.017), decreased recurrence rate (2.6% vs 12.2%, p = 0.001), and lower new hypopituitarism rate (28.9% vs 57.1%, p = 0.008). The recurrence-free survival in patients with Q-CPs was also significantly different between surgical groups (log-rank test, p = 0.037). The EEA required longer surgical time for T-CPs (p = 0.01).

CONCLUSIONS: CPs could be effectively treated by radical surgery with favorable results. Both TCA and EEA have their advantages and limitations when used to manage different types of tumors. Individualized surgical strategies based on tumor growth patterns are mandatory to achieve optimal outcomes.

PMID:33668037 | DOI:10.3171/2020.7.JNS20257

J Neurosurg. 2021 Mar 5:1-9. doi: 10.3171/2020.9.JNS201109. Online ahead of print.

ABSTRACT

OBJECTIVE: In transcranial magnetic resonance imaging-guided focused ultrasound (TcMRgFUS), a high skull density ratio (SDR) is advantageous to achieve a sufficiently high temperature at the target. However, it is not easy to estimate the temperature rise because the SDR shows different values depending on the reconstruction filter used. The resolution characteristic of a computed tomography (CT) image depends on a modulation transfer function (MTF) defined by the reconstruction filter. Differences in MTF induce unstable SDRs. The purpose of this study was both to standardize SDR by developing a method to correct the MTF and to enable effective patient screening prior to TcMRgFUS treatment and more accurate predictions of focal temperature.

METHODS: CT images of a skull phantom and five subjects were obtained using eight different reconstruction filters. A frequency filter (FF) was calculated using the MTF of each reconstruction filter, and the validity of SDR standardization was evaluated by comparing the variation in SDR before and after FF correction. Subsequently, FF processing was similarly performed using the CT images of 18 patients who had undergone TcMRgFUS, and statistical analyses were performed comparing the relationship between the SDRs before and after correction and the maximum temperature in the target during TcMRgFUS treatment.

RESULTS: The FF was calculated for each reconstruction filter based on one manufacturer’s BONE filter. In the CT images of the skull phantom, the SDR before FF correction with five of the other seven reconstruction filters was significantly smaller than that with the BONE filter (p < 0.01). After FF correction, however, a significant difference was recognized under only one condition. In the CT images of the five subjects, variation of the SDR due to imaging conditions was significantly improved after the FF correction. In 18 cases treated with TcMRgFUS, there was no correlation between SDR before FF correction and maximum temperature (rs = 0.31, p > 0.05); however, a strong positive correlation was observed after FF correction (rs = 0.71, p < 0.01).

CONCLUSIONS: After FF correction, the difference in SDR due to the reconstruction filter used is smaller, and the correlation with temperature is stronger. Therefore, the SDR can be standardized by applying the FF, and the maximum temperature during treatment may be predicted more accurately.

PMID:33668032 | DOI:10.3171/2020.9.JNS201109

J Neurosurg Pediatr. 2021 Mar 5:1-8. doi: 10.3171/2020.9.PEDS20606. Online ahead of print.

ABSTRACT

OBJECTIVE: The goal of this study was to identify the independent risk factors for recurrence or progression of pediatric craniopharyngioma and to establish predictors of the appropriate timing of intervention and best management strategy in the setting of recurrence/progression, with the aim of optimizing tumor control.

METHODS: This is a retrospective cohort study of all pediatric patients with craniopharyngioma who were diagnosed and treated at Boston Children’s Hospital between 1990 and 2017. This study was approved by the institutional review board at Boston Children’s Hospital. All statistical analyses were performed using Stata software.

RESULTS: Eighty patients (43 males and 37 females) fulfilled the inclusion criteria. The mean age at the time of diagnosis was 8.6 ± 4.4 years (range 1.2-19.7 years). The mean follow-up was 10.9 ± 6.5 years (range 1.3-24.6 years). Overall, 30/80 (37.5%) patients developed recurrence/progression. The median latency to recurrence/progression was 12.75 months (range 3-108 months). Subtotal resection with no adjuvant radiotherapy (p < 0.001) and fine calcifications (p = 0.008) are independent risk factors for recurrence/progression. An increase (%) in the maximum dimension of the tumor at the time of recurrence/progression was considered a statistically significant predictor of the appropriate timing of intervention.

CONCLUSIONS: Based on the identified independent risk factors for tumor recurrence/progression and the predictors of appropriate timing of intervention in the setting of recurrence/progression, the authors propose an algorithm for optimal management of recurrent pediatric craniopharyngioma to increase the likelihood of tumor control.

PMID:33668031 | DOI:10.3171/2020.9.PEDS20606

J Phys Act Health. 2021 Mar 5:1-8. doi: 10.1123/jpah.2020-0666. Online ahead of print.

ABSTRACT

BACKGROUND: Physical inactivity is often reported in youth and differs among boys and girls. The aim of this study is to assess sex/gender considerations in intervention studies promoting physical activity and reducing sedentary behavior in youth using a sex/gender checklist.

METHODS: A systematic search was conducted in August 2018 to identify all relevant controlled trials. Studies screened must have reported a quantified measure of physical activity and/or sedentary behavior, and identified participants by sex/gender at baseline. For evaluation of the sex/gender consideration, the authors used a sex/gender checklist developed by expert consensus.

RESULTS: The authors reviewed sex/gender considerations in all aspects of intervention development, implementation, and evaluation in 217 studies. Sex/gender aspects were only rudimentarily taken into account, most frequently during statistical analyses, such as stratification or interaction analysis.

CONCLUSIONS: Sex/gender effects are not sufficiently reported. To develop guidelines that are more inclusive of all girls and boys, future interventions need to document sex/gender differences and similarities, and explore whether sex/gender influences different phases of intervention programs. The newly developed sex/gender checklist can hereby be used as a tool and guidance to adequately consider sex/gender in the several steps of intervention planning, implementation, and evaluation.

PMID:33668018 | DOI:10.1123/jpah.2020-0666

JMIR Public Health Surveill. 2021 Feb 26. doi: 10.2196/27091. Online ahead of print.

ABSTRACT

BACKGROUND: Several studies reported a low prevalence of current smoking among hospitalized COVID-19 cases however, no definitive conclusions can be drawn.

OBJECTIVE: We investigated the association of tobacco smoke exposure with the nasopharyngeal swab (NPS) test result for SARS-CoV-2 infection and the disease severity accounting for possible confounders.

METHODS: The nationwide self-administered cross-sectional EPICOVID19 web-based survey was performed in an Italian population of 198,822 voluntary adults who filled in an online questionnaire between April 13 and June 2, 2020. For the present study, we analyzed 6857 individuals with known NPS test result. The associations of smoking status and the dose-response relationship with the positivity to NPS test and infection severity were calculated as odds ratios with 95% Confidence Intervals (OR, 95%CI) by means of analyzed using logistic and multinomial regression models adjusting for socio-demographic, clinical, and behavioral characteristics.

RESULTS: Out of the 6857 individuals (mean age 47.9 years, 65.9% females), 63.2% had never smoked, 21.3% were former and 15.5% were current smokers. Compared to non-smokers, current smokers were younger, more educated, less affected by chronic diseases, reported less frequently COVID-like symptoms, were less hospitalized and tested for COVID-19. In multivariate analysis current smokers had almost halved odds of a positive NPS test (OR 0.54, 95% CI 0.45-0.65) compared to non-smokers. We also found a dose-dependent relationship with tobacco smoke: mild smokers (OR 0.76, 95% CI 0.55-1.05), moderate (OR 0.56, 95% CI 0.42-0.73) and heavy smokers (OR 0.38, 95% CI 0.27-0.53). This inverse association persisted also when considering the severity of the infection. Current smokers had a statistically significant lower probability of having asymptomatic (OR 0.50 95%CI 0.27-0.92), mild (OR 0.65 95%CI 0.53-0.81), and severe infection (OR 0.27 95%CI 0.17-0.42) compared to never smokers.

CONCLUSIONS: Current smoking was negatively associated with SARS-CoV-2 infection with a dose-dependent relation. Ad-hoc experimental studies are needed to elucidate the mechanisms underlying this association.

CLINICALTRIAL: ClinicalTrials.gov NCT04471701.

PMID:33668011 | DOI:10.2196/27091

Vet Parasitol. 2021 Feb 15;291:109387. doi: 10.1016/j.vetpar.2021.109387. Online ahead of print.

ABSTRACT

With the trend to organic production and concerns about using antibiotic feed additives, the control of infections with Eimeria spp. in broiler flocks has become more difficult. Vaccination against coccidia is an alternative, but there are concerns that the live vaccines used might have negative effects on production parameters and intestinal health. Reports of experiments directly comparing anticoccidial drugs and anticoccidial vaccines are rare. This network meta-analysis (NMA) identified and analyzed 61 articles reporting 63 experiments testing anticoccidial drugs and anticoccidial vaccines under conditions resembling commercial broiler production. The effect sizes were mean differences in body weight/body weight gain (BW/BWG) and feed conversion rate (FCR) between the 175 included groups. The results show that groups vaccinated against coccidia have a similar BW/BWG and FCR at processing age compared to groups given anticoccidial drugs. However, the results tended to be more favorable for anticoccidial drugs than for vaccines. The analysis of eight subsets, containing only groups (1) groups that had not received an AGP in addition to an anticoccidial drug, (2) groups that had not received ionophores, (3) groups that had not received chemicals, (4) groups that had not received an attenuated vaccine, (5) groups that had not received a fully virulent vaccine, (6) groups that were not additionally challenged with bacteria or not challenged, (7) groups that had received a severe challenge as defined by a total infection dose of more than 100,000 oocysts or were not challenged, (8) groups that were challenged on day 15 or earlier or not challenged brought similar results and confirmed the robustness of the NMA. In addition, the analysis exposes unnecessary, as well as inherent, problems with data quality, which every researcher working with coccidia should carefully consider, and identifies under-researched areas that should be addressed in future research.

PMID:33667988 | DOI:10.1016/j.vetpar.2021.109387

Cognition. 2021 Mar 2;210:104580. doi: 10.1016/j.cognition.2020.104580. Online ahead of print.

ABSTRACT

Comparison of different lines of research on statistical intuitions and probabilistic reasoning reveals several puzzling contradictions. Whereas babies seem to be intuitive statisticians, surprisingly capable of statistical learning and inference, adults’ statistical inferences have been found to be inconsistent with the rules of probability theory and statistics. Whereas researchers in the 1960s concluded that people’s probability updating is “conservatively” proportional to normative predictions, probability updating research in the 1970s suggested that people are incapable of following Bayes’s rule. And whereas animals appear to be strikingly risk savvy, humans often seem “irrational” when dealing with probabilistic information. Drawing on research on the description-experience gap in risky choice, we integrate and systematize these findings from disparate fields of inquiry that have, to date, operated largely in parallel. Our synthesis shows that a key factor in understanding inconsistencies in statistical intuitions research is whether probabilistic inferences are based on symbolic, abstract descriptions or on the direct experience of statistical information. We delineate this view from other conceptual accounts, consider potential mechanisms by which attributes of first-hand experience can facilitate appropriate statistical inference, and identify conditions under which they improve or impair probabilistic reasoning. To capture the full scope of human statistical intuition, we conclude, research on probabilistic reasoning across the lifespan, across species, and across research traditions must bear in mind that experience and symbolic description of the world may engage systematically distinct cognitive processes.

PMID:33667974 | DOI:10.1016/j.cognition.2020.104580