Nevin Manimala

Med Phys. 2021 Nov 1. doi: 10.1002/mp.15316. Online ahead of print.

ABSTRACT

PURPOSE: Clinical indicators of histological information are important for breast cancer treatment and operational decision making, but these histological data suffer from frequent missing values due to various experimental/clinical reasons. The limited amount of histological information from breast cancer samples impedes the accuracy of data imputation. The purpose of this study was to impute missing histological data, including Ki-67 expression level, luminal A subtype, and histological grade, by integrating tumor radiomics.

METHODS: To this end, a deep matrix completion (DMC) method was proposed for imputing missing histological data using nonmissing features composed of histological and tumor radiomics (termed radiohistological features). DMC finds a latent nonlinear association between radiohistological features across all samples and samples for all the features. Radiomic features of morphologic, statistical and texture features were extracted from dynamic enhanced magnetic imaging (DCE-MRI) inside the tumor. Experiments on missing histological data imputation were performed with a variable number of features and missing data rates. The performance of the DMC method was compared with those of the nonnegative matrix factorization (NMF) and collaborative filtering (MCF)-based data imputation methods. The area under the curve (AUC) was used to assess the performance of missing histological data imputation.

RESULTS: By integrating radiomics from DCE-MRI, the DMC method showed significantly better performance in terms of AUC than that using only histological data. Additionally, DMC using 120 radiomic features showed an optimal prediction performance (AUC = 0.793), which was better than the NMF (AUC = 0.756) and MCF methods (AUC = 0.706; corrected p = 0.001). The DMC method consistently performed better than the NMF and MCF methods with a variable number of radiomic features and missing data rates.

CONCLUSIONS: DMC improves imputation performance by integrating tumor histological and radiomics data. This study transforms latent imaging-scale patterns for interactions with molecular-scale histological information and is promising in the tumor characterization and management of patients. This article is protected by copyright. All rights reserved.

PMID:34724248 | DOI:10.1002/mp.15316

Laryngoscope. 2021 Nov 1. doi: 10.1002/lary.29935. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the effect of povidone-iodine (PVP-I) nasal sprays on nasopharyngeal (NP) viral load as assessed by cycle threshold on quantitative polymerase chain reaction (qPCR) of SARS-CoV-2 in outpatients.

STUDY DESIGN: Three arm, triple blinded, randomized, placebo-controlled clinical trial.

METHODS: Participants were randomized within 5 days of testing positive for COVID-19 to receive nasal sprays containing either placebo (0.9% saline), 0.5% PVP-I, or 2.0% PVP-I. NP swabs for qPCR analysis were taken at baseline, 1-hour post-PVP-I spray (2 sprays/nostril), and 3 days post-PVP-I spray (20 sprays/nostril). Symptom and adverse event questionnaires were completed at baseline, day 3, and day 5. University of Pennsylvania Smell Identification Tests (UPSIT) were completed at baseline and day 30.

RESULTS: Mean cycle threshold (Ct) values increased over time in all groups, indicating declining viral loads, with no statistically significant difference noted in the rate of change between placebo and PVP-I groups. 2.0% PVP-I group showed statistically significant improvement in all symptom categories, however also reported a high rate of nasal burning. Olfaction via UPSIT showed improvement by at least one category in all groups. There were no hospitalizations or mortalities within 30 days of study enrollment.

CONCLUSION: Saline and low concentration PVP-I nasal sprays are well tolerated. Similar reductions in SARS-CoV-2 nasopharyngeal viral load were seen over time in all groups. All treatment groups showed improvement in olfaction over 30 days. These data suggest that dilute versions of PVP-I nasal spray are safe for topical use in the nasal cavity, but that PVP-I does not demonstrate virucidal activity in COVID-19 positive outpatients. This article is protected by copyright. All rights reserved.

PMID:34724213 | DOI:10.1002/lary.29935

Int J Cancer. 2021 Nov 1. doi: 10.1002/ijc.33862. Online ahead of print.

ABSTRACT

High citrus consumption may increase melanoma risk; however, little is known about the biological mechanisms of this association, or whether it is modified by genetic variants. We conducted a genome-wide analysis of gene-citrus consumption interactions on melanoma risk among 1,563 melanoma cases and 193,296 controls from the UK Biobank. Both the 2-degrees-of-freedom (df) joint test of genetic main effect and gene-environment (G-E) interaction and the standard 1-df G-E interaction test were performed. Three index SNPs (lowest p-value SNP among highly correlated variants [r² >0.6]) were identified from among the 365 genome-wide significant 2-df test results (rs183783391 on chromosome 3 [MITF], rs869329 on chromosome 9 [MTAP], rs11446223 on chromosome 16 [DEF8]). Although all three were statistically significant for the 2-df test (4.25e-08, 1.98e-10, and 4.93e-13, respectively), none showed evidence of interaction according to the 1-df test (p=0.73, 0.24, 0.12, respectively). Eight non-index, 2-df test significant SNPs on chromosome 16 were significant (p<.05) according to the 1-df test, providing evidence of citrus-gene interaction. Seven of these SNPs were mapped to AFG3L1P (rs199600347, rs111822773, rs113178244, rs3803683, rs73283867, rs78800020, rs73283871), and one SNP was mapped to GAS8 (rs74583214). We identified several genetic loci that may elucidate the association between citrus consumption and melanoma risk. Further studies are needed to confirm these findings. This article is protected by copyright. All rights reserved.

PMID:34724200 | DOI:10.1002/ijc.33862

Reprod Sci. 2021 Nov 1. doi: 10.1007/s43032-021-00767-0. Online ahead of print.

ABSTRACT

Unexplained infertile couples can have further expectant management before starting assisted reproductive treatments. However, ovarian reserve and in vitro fertilization (IVF) outcomes rapidly decline after 39 years or more. It is thus important to clarify whether a waiting policy is also appropriate for women of advanced age. Couples who had access to a waiting list for approximately 1 year before receiving reimbursed public IVF were compared with those paying for access to immediate treatment. To allow for comparisons between these two strategies, we followed up couples who opted to pay for 1 year after the last embryo transfer from their first cycle. We calculated the proportion of live births in both groups and compared these using logistic regression models and a two-sample Z test for equality of proportions. Six hundred thirty-five couples were evaluated. Out of 359 couples in the immediate group, 70 (19.5%) had a live birth of which 11 after natural conception and 59 after IVF. Out of 276 couples in the waiting group, 57 (20.7%) had a live birth of which 37 after natural conception and 20 after IVF. There was no statistically significant difference between the two strategies in terms of the crude cumulative live birth rate (cLBR). The adjusted odds ratio of 0.69 (95%CI:0.39-1.22) did not change this conclusion as our sensitivity analyses. The cLBR for the ‘waiting before IVF’ and the ‘immediate’ strategies were similar. Further studies are needed to better characterize couples affected by unexplained infertility in order to individualize treatment strategies.

PMID:34724170 | DOI:10.1007/s43032-021-00767-0

Radiol Med. 2021 Nov 1. doi: 10.1007/s11547-021-01422-z. Online ahead of print.

ABSTRACT

PURPOSE: Aim of this study is to assess the ability of contrast-enhanced CT image-based radiomic analysis to predict local response (LR) in a retrospective cohort of patients affected by pancreatic cancer and treated with stereotactic body radiation therapy (SBRT). Secondary aim is to evaluate progression free survival (PFS) and overall survival (OS) at long-term follow-up.

METHODS: Contrast-enhanced-CT images of 37 patients who underwent SBRT were analyzed. Two clinical variables (BED, CTV volume), 27 radiomic features were included. LR was used as the outcome variable to build the predictive model. The Kaplan-Meier method was used to evaluate PFS and OS.

RESULTS: Three variables were statistically correlated with the LR in the univariate analysis: Intensity Histogram (StdValue feature), Gray Level Cooccurrence Matrix (GLCM25_Correlation feature) and Neighbor Intensity Difference (NID25_Busyness feature). Multivariate model showed GLCM25_Correlation (P = 0.007) and NID25_Busyness (P = 0.03) as 2 independent predictive variables for LR. The odds ratio values of GLCM25_Correlation and NID25_Busyness were 0.07 (95%CI 0.01-0.49) and 8.10 (95%CI 1.20-54.40), respectively. The area under the curve for the multivariate logistic regressive model was 0.851 (95%CI 0.724-0.978). At a median follow-up of 30 months, median PFS was 7 months (95%CI 6-NA); median OS was 11 months (95%CI 10-22 months).

CONCLUSIONS: This analysis identified a radiomic signature that correlates with LR. To confirm these results, prospective studies could identify patient sub-groups with different rates of radiation dose-response to define a more personalized SBRT approach.

PMID:34724139 | DOI:10.1007/s11547-021-01422-z

Graefes Arch Clin Exp Ophthalmol. 2021 Nov 1. doi: 10.1007/s00417-021-05466-9. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to determine the 5-year visual field progression and identify the prognostic factors for progression in Malay patients with primary glaucoma.

METHODS: A retrospective cohort record review study was conducted among 222 patients (222 eyes) with primary glaucoma who were selected from a glaucoma research database of a tertiary center in Malaysia. The patients were Malays and diagnosed with primary open-angle glaucoma (POAG) or primary angle-closure glaucoma (PACG). Patients who were followed up regularly for at least 6 months between 1 January 2009 and 31 December 2014 and completed another 1-year follow-up after recruitment (between 1 January 2015 and 31 December 2015) were selected. Multiple prognostic factors that influence visual field progression were identified. Progression of visual field loss was based on the Advanced Glaucoma Intervention Study and Hodapp-Parrish-Anderson scores. Kaplan-Meier survival and Cox proportional hazard regression analyses were performed.

RESULTS: Sixty-three patients (28.4%) developed visual field progression after a mean (SD) follow-up of 6.9 (3.3) years. Those with POAG progressed faster (mean time, 10.6 years; 95% confidence interval [CI], 9.3, 11.9) than those with PACG (17.3 years; 95% CI, 14.8, 19.9) but not statistically significant. Disc hemorrhage and history of eye pain increased the risk of progression by 2.8-folds (95% CI, 1.6, 4.8) and 2.5-folds (1.4, 4.4), respectively.

CONCLUSION: The 5-year survival of the Malay primary glaucoma patients with visual field progression was similar with that of other Asian populations. However, aggressive management is required for those with disc hemorrhages and eye pain related to increased intraocular pressure.

PMID:34724110 | DOI:10.1007/s00417-021-05466-9

Strahlenther Onkol. 2021 Nov 1. doi: 10.1007/s00066-021-01866-2. Online ahead of print.

ABSTRACT

PURPOSE: Randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regime PATIENTS AND METHODS: Patients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice weekly; experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used.

RESULTS: A total of 64 knees and 172 hands were randomized. 3.0 Gy was applied to 87 hands and 34 knees, 0.3 Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3 Gy and after 0.3 Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment.

CONCLUSION: We found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3 Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders.

PMID:34724085 | DOI:10.1007/s00066-021-01866-2

Obstet Gynecol Surv. 2021 Oct;76(10):634-643. doi: 10.1097/OGX.0000000000000943.

ABSTRACT

IMPORTANCE: Substance use during pregnancy is a major health issue for both the mother and the fetus, but it also represents an important public health concern.

OBJECTIVE: The aim of this review was to summarize and compare recommendations from recently published guidelines on substance use during pregnancy and especially regarding alcohol, smoking, and drug use.

EVIDENCE ACQUISITION: A descriptive review of guidelines from the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, the World Health Organization (WHO), the Society of Obstetricians and Gynaecologists of Canada, and the American College of Obstetricians and Gynecologists on substance use was conducted. Regarding the term “substance use,” the most recently published Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition substances were used.

RESULTS: All the reviewed guidelines recommend appropriate counseling and screening women regarding alcohol, smoking, and drug use during the antenatal period, while the management options vary. More specifically, the prompt management of alcohol dependence is emphasized by all the guidelines except from the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, which makes no recommendation upon. The use of alcohol during breastfeeding should be avoided. Regarding smoking cessation, all guidelines recommend the use of certain psychosocial, behavioral interventions, and pharmacotherapy. All the guidelines, except the one from the WHO, suggest screening drug users for coexistent sexually transmitted infections. Brief interventions are considered beneficial, while a gradual decrease in benzodiazepines is suggested, as well as the discontinuation of marijuana and methamphetamine use. However, there is controversy regarding breastfeeding in those women as the WHO recommends in favor, whereas the Society of Obstetricians and Gynaecologists of Canada and the American College of Obstetricians and Gynecologists recommend against this practice. Finally, all the guidelines state that, following delivery, close monitoring of the neonate is needed.

CONCLUSIONS: The diversity of guidelines’ recommendations concerning substance use reflects the different ways of the management of pregnant women during routine antenatal care due to absence of strong evidence. More research in the areas of dispute may allow the adoption of an international consensus, in order to early detect and appropriately manage pregnant women with harmful addictions.

PMID:34724075 | DOI:10.1097/OGX.0000000000000943

Andrology. 2021 Nov 1. doi: 10.1111/andr.13123. Online ahead of print.

ABSTRACT

BACKGROUND: An explosive increase in couples attending assisted reproductive technologies (ART) has been recently observed, despite an overall success rate about 20-30%. Considering the ART-related economic and psycho-social costs, the improvement of these percentages is extremely relevant. However, in the identification of predictive markers of ART success, male parameters are largely underestimated so far.

STUDY DESIGN: Retrospective, observational study.

OBJECTIVES: To evaluate whether conventional semen parameters could predict the ART success MATERIALS AND METHODS: All couples attending a single third-level Fertility Centre from 1992 to 2020 were retrospectively enrolled, collecting all semen and ART parameters of fresh cycles. Fertilization rate (FR) was the primary end-point, representing a parameter immediately dependent from male contribution. Pregnancy and live birth rates were considered in relation to semen variables. Statistical analyses were performed using the parameters obtained according to WHO manual edition used for semen analysis.

RESULTS: 22013 in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles were considered. Overall, FR was significantly lower in patients with abnormal semen parameters compared to normozoospermic men, irrespective to the WHO manual edition. In the IVF setting, both progressive motility (p = 0.012) and motility after capacitation (p = 0.002) significantly predicted fertilization rate (statistical accuracy = 71.1%). Sperm motilities predicted also pregnancy (p<0.001) and live birth (p = 0.001) rates. In ICSI cycles, sperm morphology predicted FR (p = 0.001, statistical accuracy = 90.3%). Sperm morphology significantly predicted both pregnancy (p<0.001) and live birth (p<0.001) rates, and a cut off of 5.5% was identified as a threshold to predict clinical pregnancy (AUC = 0.811, p<0.001).

DISCUSSION: Interestingly, sperm motility plays a role in predicting IVF success, while sperm morphology is the relevant parameter in ICSI cycles. These parameters may be considered reliable tools to measure the male role on ART outcomes, potentially impacting the clinical management of infertile couples. This article is protected by copyright. All rights reserved.

PMID:34723422 | DOI:10.1111/andr.13123

J Magn Reson Imaging. 2021 Nov 1. doi: 10.1002/jmri.27979. Online ahead of print.

ABSTRACT

BACKGROUND: Despite concerns about safety, gadolinium-based contrast agents (GBCAs) are still used for abdominal and pelvic imaging during pregnancy. Researchers have mainly focused on teratogenicity, while very little is known about their possible direct effects on uterine contractility, yet free gadolinium potentially impacts contractility through interaction with calcium channels.

PURPOSE: To investigate possible effects of selected GBCAs (namely gadoteridol, gadoversetamide, gadobutrol, gadoterate meglumine, and gadoxetic acid) on the contractility of rat myometrium.

STUDY TYPE: In vitro organ bath study.

ANIMAL MODEL: Myometria were isolated from adult (10-12 weeks old) Sprague Dawley rats, both pregnant (N = 8) and nonpregnant (N = 36).

FIELD STRENGTH/SEQUENCE: NA.

ASSESSMENT: Myometrial strips were suspended in tissue bath containing physiological saline and isometric contractions were recorded. GBCAs were added to the tissue bath cumulatively, and their effects on contractility parameters (quantified by amplitude, frequency, and area under contractility curve [AUC]) were evaluated by 10-minute intervals.

STATISTICAL TESTS: Normality data, checked by Shapiro-Wilk test, were transformed by arcsine when needed. One- or two-way analysis of variance was performed, where appropriate, followed by Student-Newman-Keuls test. A P value of <0.05 was considered statistically significant.

RESULTS: All of the assayed GBCAs elicited some alterations in the myometrial contractility in a concentration-dependent manner. Gadoterate meglumine, gadoxetic acid, and gadoversetamide caused a concentration-dependent significant attenuation in AUC (oxytocin-induced, from 100% during control period to 45.1 ± 9.0% (nonpregnant) and 59.9 ± 8.5% (pregnant), for 90 μM gadoterate meglumine; respectively), and frequency of the spontaneous and oxytocin-induced contractions. Gadobutrol and gadoteridol at highest dose significantly attenuated mean AUC and frequency of oxytocin-induced contractions of nonpregnant myometrium.

DATA CONCLUSION: Results from this in vitro study indicate that GBCAs elicit modulation of myometrial contractions at clinically relevant concentrations. These effects may account, at least partially, for the known potential side effects (rare cases of miscarriages and elective abortion) of these agents.

LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.

PMID:34723414 | DOI:10.1002/jmri.27979