Nevin Manimala

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

J Magn Reson Imaging. 2021 Nov 1. doi: 10.1002/jmri.27977. Online ahead of print.

ABSTRACT

BACKGROUND: Amide proton transfer weighted imaging (APTw), intravoxel incoherent motion (IVIM), and positron emission tomography (PET) imaging all have the potential to characterize solitary pulmonary lesions (SPLs).

PURPOSE: To compare APTw and IVIM with PET imaging for distinguishing between benign and malignant SPLs and their subtypes.

STUDY TYPE: Prospective.

POPULATION: Ninety-five patients, 78 with malignant SPLs (including 48 with adenocarcinoma [AC] and 17 with squamous cell carcinoma [SCC]), and 17 with benign SPLs.

FIELD STRENGTH/SEQUENCE: Fast spin-echo (FSE) T2WI, FSE APTw and echo-planar imaging IVIM, MR-base attenuation correction (MRAC), and PET imaging on a 3-T whole-body PET/MR system.

ASSESSMENT: The magnetization transfer ratio asymmetry (MTRasym) at 3.5 ppm, diffusion coefficient (D), pseudo diffusion coefficient (D*), perfusion fraction (f), and the maximum standardized uptake value (SUVmax) were analyzed.

STATISTICAL TESTS: Individual sample t-test, Delong test, Pearson’s correlation analysis, and area under the receiver operating characteristic curve (AUC). P < 0.05 indicated statistical significance.

RESULTS: The MTRasym and SUVmax were significantly higher, and D was significantly lower in the malignant group (3.3 ± 2.6 [%], 7.8 ± 5, and 1.2 ± 0.3 [×10^-3 mm² /second]) compared to the benign group (-0.3 ± 1.6 [%], 3.1 ± 3.8, and 1.6 ± 0.3 [×10^-3 mm² /second]). The MTRasym and D were significantly lower, and SUVmax was significantly higher in the SCC group (0.8 ± 1.0 [%], 1.0 ± 0.2 [×10^-3 mm² /second] than in the AC group (4.1 ± 2.6 [%], 1.3 ± 0.3 [×10^-3 mm² /second], 6.7 ± 4.6). Besides, the combination (AUC = 0.964) of these three methods showed higher diagnostic efficacy than any individual method (AUC = 0.917, 0.851, 0.82, respectively) in identifying malignant and benign SPLs. However, APTw showed better diagnostic efficacy than the combination of three methods or PET imaging alone in distinguishing SCC and AC groups (AUC = 0.934, 0.781, 0.725, respectively).

DATA CONCLUSION: APTw, IVIM, and PET imaging are all effective methods to distinguish benign and malignant SPLs and their subtypes. APTw is potentially more capable than PET imaging of distinguishing lung SCC from AC.

LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

PMID:34723413 | DOI:10.1002/jmri.27977

J Women’s Health Care Manag. 2021;2(2). doi: 10.47275/2692-0948-121. Epub 2021 Mar 27.

ABSTRACT

BACKGROUND: The extent to which smoking and drinking in a local community is associated with nutrition and Z-scores of infants from spontaneous preterm deliveries, is uncertain.

AIM: To investigate associations of different levels of maternal smoking and drinking in spontaneous preterm birth with infant birthweight Z-scores.

METHODS: Information, including gestational age (determined by earliest ultrasound), maternal arm circumference (measured at enrolment), smoking-drinking data (obtained up to 4 occasions), birthweight data (obtained from medical records) and birthweight Z-scores (calculated from INTERGROWTH- 21st study), collected over a period of nine years was used to compare 407 spontaneous preterm births with 3 493 spontaneous term births Analyses of variance, correlations and multiple regression were performed in STATISTICA.

RESULTS: Women with spontaneous preterm birth, had significantly lower gravidity and smaller arm circumference when compared to women with spontaneous birth at term. Women with spontaneous preterm birth drank more and heavier during pregnancy, and more smoked. Gestational age at birth was significantly longer in heavy-smokers-heavy-drinkers compared to heavy-smokers-no-drinkers (7.1 days) and in no-smokers-heavy-drinkers when compared to no-smokers-no-drinkers (11.2 days). Birthweight was significantly lower in low-smokers-heavy-drinkers when compared to low-smokers-no-drinkers (240g) and in heavy-smokers-low-drinkers when compared to no-smokers-low-drinkers (273g). Birthweight Z-scores were significantly lower in low-smokers-heavy-drinkers when compared to low-smokers-low-drinkers and low-smokers-no-drinkers; and, also significantly lower in heavy-smokers-low-drinkers when compared to low-smokers-low-drinkers and no-smokers-low-drinkers.

CONCLUSION: Alcohol aggravates the detrimental effect of smoking on birthweight and birthweight Z-scores but seems to counteract the negative association of smoking with gestational age.

PMID:34723283 | PMC:PMC8553154 | DOI:10.47275/2692-0948-121

JACS Au. 2021 Jul 22;1(10):1708-1718. doi: 10.1021/jacsau.1c00300. eCollection 2021 Oct 25.

ABSTRACT

This work considers the evaluation of density functional theory (DFT) when comparing against experimental observations of CO binding trends on the strong binding Pt(111) and intermediate binding Cu(111) and for weak binding Ag(111) and Au(111) surfaces important in electrocatalysis. By introducing thermal fluctuations using appropriate statistical mechanical NVT and NPT ensembles, we find that the RPBE and B97M-rV DFT functionals yield qualitatively better metal surface strain trends and CO enthalpies of binding for Cu(111) and Pt(111) than found at 0 K, thereby correcting the overbinding by 0.2 to 0.3 eV to yield better agreement with the enthalpies determined from experiment. The importance of dispersion effects are manifest for the weak CO binding Ag(111) and Au(111) surfaces at finite temperatures in which the RPBE functional does not bind CO at all, while the B97M-rV functional shows that the CO-metal interactions are a mixture of chemisorbed and physisorbed species with binding enthalpies that are within ∼0.05 eV of experiment. Across all M(111) surfaces, we show that the B97M-rV functional consistently predicts the correct atop site preference for all metals due to thermally induced surface distortions that preferentially favor the undercoordinated site. This study demonstrates the need to fully account for finite temperature fluctuations to make contact with the binding enthalpies from surface science experiments and electrocatalysis applications.

PMID:34723274 | PMC:PMC8549055 | DOI:10.1021/jacsau.1c00300

JACS Au. 2021 Aug 26;1(10):1556-1571. doi: 10.1021/jacsau.1c00297. eCollection 2021 Oct 25.

ABSTRACT

Polymers with precisely defined monomeric sequences present an exquisite tool for controlling material properties by harnessing both the robustness of synthetic polymers and the ability to tailor the inter- and intramolecular interactions so crucial to many biological materials. While polymer scientists traditionally synthesized and studied the physics of long molecules best described by their statistical nature, many biological polymers derive their highly tailored functions from precisely controlled sequences. Therefore, significant effort has been applied toward developing new methods of synthesizing, characterizing, and understanding the physics of non-natural sequence-defined polymers. This perspective considers the synergistic advantages that can be achieved via tailoring both precise sequence control and attributes of traditional polymers in a single system. Here, we focus on the potential of sequence-defined polymers in highly associating systems, with a focus on the unique properties, such as enhanced proton conductivity, that can be attained by incorporating sequence. In particular, we examine these materials as key model systems for studying previously unresolvable questions in polymer physics including the role of chain shape near interfaces and how to tailor compatibilization between dissimilar polymer blocks. Finally, we discuss the critical challenges-in particular, truly scalable synthetic approaches, characterization and modeling tools, and robust control and understanding of assembly pathways-that must be overcome for sequence-defined polymers to attain their potential and achieve ubiquity.

PMID:34723259 | PMC:PMC8549048 | DOI:10.1021/jacsau.1c00297

JPGN Rep. 2021 May;2(2):e077. doi: 10.1097/PG9.0000000000000077.

ABSTRACT

OBJECTIVES: The relationship between vitamin D deficiency (VDD) and pediatric nonalcoholic fatty liver disease (NAFLD) remains uncertain due to conflicting results and few studies with histologic endpoints. We therefore used multiple imaging and histologic NAFLD endpoints to more comprehensively assess the association between VDD and NAFLD in a large pediatric population.

METHODS: Data were obtained from an ongoing pediatric NAFLD study in Bronx, NY. Briefly, overweight and obese children aged 2-18 years with alanine aminotransferase (ALT) levels ≥ 35 U/L were serially enrolled. Liver biopsy was obtained in accordance with clinical guidelines. All participants had liver imaging, namely, controlled attenuation parameter (CAP; Echosens, France) to assess steatosis and, to assess fibrosis, vibration controlled transient elastography (VCTE; FibroScan™, Echosens, France) and acoustic radiation force impulse (ARFI; Philips, Netherlands) imaging. Levels of 25-hydroxyvitamin D were measured serologically.

RESULTS: N=276 (88%) of 315 participants had 25-OH vitamin D results, of whom 241 (87%) were Hispanic, 199 (72%) were male, and 92 (33%) underwent liver biopsy. VDD was univariately associated with high waist circumference (p=0.004), high-density lipoprotein level (p=0.01), season (p=0.009), and CAP score (p=0.01). In multivariate analysis, only waist circumference (p=0.0002) and biopsy inflammation grade (p=0.03) were associated with VDD, though the latter had not approximated statistical significance in univariate analysis (p=0.56). There was no association between VDD and hepatic steatosis, ballooning, NAFLD Activity Score, ARFI or VCTE elasticity scores.

CONCLUSIONS: VDD was not associated with NAFLD defined by imaging and histologic endpoints, except for a possible relation with histologic inflammation grade.

PMID:34723254 | PMC:PMC8553135 | DOI:10.1097/PG9.0000000000000077

Glomerular Dis. 2021 Aug;1(3):105-117. doi: 10.1159/000516832. Epub 2021 Jun 24.

ABSTRACT

INTRODUCTION: Disparities in health-related quality of life (HRQOL) have been inadequately studied in patients with glomerular disease. The aim of this study was to identify relationships between race/ethnicity, socioeconomic status, disease severity, and HRQOL in an ethnically and racially diverse cohort of patients with glomerular disease.

METHODS: Cure Glomerulonephropathy (CureGN) is a multinational cohort study of patients with biopsy-proven glomerular disease. Associations between race/ethnicity and HRQOL were determined by the following: 1. Missed school or work due to kidney disease; 2. Responses to Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires. We adjusted for demographics, socioeconomic status, and disease characteristics using multivariable logistic and linear regression.

RESULTS: Black and Hispanic participants had worse socioeconomic status and more severe glomerular disease than White or Asian participants. Black adults missed work or school most frequently due to kidney disease (30% versus 16-23% in the other three groups, p=0.04), and had the worst self-reported global physical health (median score 44.1 versus 48.0-48.2, p<0.001) and fatigue (53.8 versus 48.5-51.1, p=0.002), compared to other racial/ethnic groups. However, these findings were not statistically significant with adjustment for socioeconomic status and disease severity, both of which were strongly associated with HRQOL in adults. Among children, disease severity but not race/ethnicity or socioeconomic status were associated with HRQOL.

CONCLUSIONS: Among patients with glomerular disease enrolled in CureGN, the worse HRQOL reported by Black adults was attributable to lower socioeconomic status and more severe glomerular disease. No racial/ethnic differences in HRQOL were observed in children.

PMID:34723246 | PMC:PMC8553235 | DOI:10.1159/000516832

Explor Res Clin Soc Pharm. 2021 Oct 26:100085. doi: 10.1016/j.rcsop.2021.100085. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the self-reported impact of the COVID-19 pandemic among final year student pharmacists enrolled in a Doctor of Pharmacy program in New York City during the first peak of the outbreak March through May 2020.

METHODS: A required senior seminar course for graduating student pharmacists served as a conduit for faculty led monitoring of the wellbeing of the cohort through three data sources: 1) polling data regarding stress factors during a COVID-19 informational session (March 2020), 2) survey data from a 12-item COVID-19 Impact Survey developed and administered electronically in May 2020 and 3) qualitative data from reflection papers mentioning COVID-19. Descriptive statistics, bivariate analysis and thematic analysis were used to summarize data.

RESULTS: In March, almost half of respondents (total = 185) reported high personal (47.6%) and school related stress (42.1%). Most students were participating in advanced pharmacy practice experiences (80%) and working in a pharmacy (80%). Survey data (n = 96) revealed the majority of participants perceived negative impact on their future career (69%) and reported concern for people close to them with suspected and confirmed COVID-19. One-third of participants reported knowing someone who died from COVID-19 and 8% were self-confirmed COVID-19 positive. Themes emerging from the reflection papers included: changed perspective, gained experience as a pharmacist during a pandemic, concern for loved ones, and positive outlook.

CONCLUSION: The COVID-19 pandemic had a significant impact on the wellbeing of a cohort of graduating student pharmacists in New York during the initial peaks of the spread in the United States. The results reinforce a need for student support during emergency situations, especially during the final year.

PMID:34723239 | PMC:PMC8547815 | DOI:10.1016/j.rcsop.2021.100085

Eur Urol Open Sci. 2021 Sep 30;33:83-88. doi: 10.1016/j.euros.2021.09.005. eCollection 2021 Nov.

ABSTRACT

BACKGROUND: Retroperitoneal lymph node dissection (RPLND) is essential for the treatment of metastatic germ cell tumours of the testis. Recommendations on the referral and management of complex urological cancers in the UK includes centralisation of services to regional centres.

OBJECTIVE: To review contemporary PC-RPLND outcomes at a high-volume centre with a complex case-mix, and compare with national registry data.

DESIGN SETTING AND PARTICIPANTS: We retrospectively reviewed the medical records of PC-RPLNDs performed for germ cell tumours at our centre between July 2012 and September 2018.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were Clavien 3+ complications, histology, rates of positive margin, relapse, in-field recurrences, and mortality. Secondary outcomes were blood loss, operation time, blood transfusion, adjuvant procedures, length of stay, and lymph node count. Surgical and histological outcomes of all RPLNDs for testicular cancers were compared with national RPLND registry data. For statistical difference, χ² testing was used.

RESULTS AND LIMITATIONS: A total of 178 procedures were performed, including 31 (17%) redo RPLNDs. Clavien 3+ complications occurred in 11 (7%). Histological findings in non-redo cases were the following: necrosis 24%, teratoma 62%, viable germ cell tumour 11%, and dedifferentiated cancers 3%. Rates of positive margin, relapse, and in-field recurrence were 11%, 17%, and 2%, respectively. Overall survival was 89% at a median of 36 mo. The median blood loss was 650 ml (350, 1250), with a transfusion rate of 8%. Nephrectomy, vascular reconstruction, and visceral resection was required in 12%, 6%, and 3% respectively. The median inpatient stay was 6 d (5, 8) and the median node count was 35 (20, 37). A comparison of all RPLNDs with national data showed no statistical difference in primary outcomes. Our blood transfusion rate was significantly lower (12% vs 21%, χ² [1, N = 322] = 4.296, p = 0.038).

CONCLUSIONS: Centralisation led to high quality of RPLND in UK. Within that, our series (the largest in the UK) demonstrates no significant difference in outcomes despite higher complexity cases. Our blood transfusion rates are in fact lower than national figures. Complex RPLNDs should be performed in high-volume centres where possible.

PATIENT SUMMARY: In the UK, retroperitoneal lymph node dissections (RPLND) are centralised to specialist centres and the quality of surgery is high, with low complications and good histological outcomes. When compared to national data, we found no significant difference in the majority of outcomes from our high-volume centre despite our complex case-mix.

PMID:34723218 | PMC:PMC8546923 | DOI:10.1016/j.euros.2021.09.005

Eur Urol Open Sci. 2021 Sep 27;33:48-55. doi: 10.1016/j.euros.2021.08.008. eCollection 2021 Nov.

ABSTRACT

BACKGROUND: Currently, metastatic hormone-sensitive prostate cancer (mHSPC) patients are often treated with docetaxel chemotherapy at the initiation of hormonal therapy. This treatment is based on the results of two pivotal trials. However, trial populations are not a representative of real-world patient populations.

OBJECTIVE: We aimed to analyze whether survival rates in our daily practice cohort is comparable with those in clinical trials and to characterize the tolerability of docetaxel chemotherapy in daily practice.

DESIGN SETTING AND PARTICIPANTS: In this retrospective cohort analysis, we studied 159 mHSPC patients treated with early docetaxel from April 2014 up to June 2020 in a top clinical hospital in The Netherlands. Patients were selected using hospital pharmacy records.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared the results of our cohort with the results of the cohorts of the two pivotal trials. We aimed to analyze the survival rates in our cohort and characterize the tolerability of docetaxel chemotherapy in daily practice.

RESULTS AND LIMITATIONS: Despite the relatively high number of comorbidities in our daily practice cohort, overall survival of our cohort showed great similarity with that of the two pivotal trials: 60.2 mo compared with 57.6 and 59.1 mo. Furthermore, early docetaxel was well tolerated in daily practice. Nearly 90% of the patients completed the full six cycles, and polyneuropathy led to relatively few dose reductions (6.9%).

CONCLUSIONS: Early docetaxel is well tolerated in daily practice. Our daily practice cohort showed great similarity in overall survival to the clinical trials. Our results might be of interest in the developing landscape of mHSPC treatment.

PATIENT SUMMARY: We studied docetaxel chemotherapy for metastatic prostate cancer in daily practice. These patients have the same survival as selected patients participating in clinical trials. Docetaxel was well tolerated in daily practice.

PMID:34723217 | PMC:PMC8546919 | DOI:10.1016/j.euros.2021.08.008