Nevin Manimala

Am J Clin Nutr. 2022 Feb 16:nqac047. doi: 10.1093/ajcn/nqac047. Online ahead of print.

ABSTRACT

BACKGROUND: High glycemic index (GI) diets have been linked to elevated risk of cardiometabolic diseases. One possible underlying mechanism comes from high GI diet’s potential to promote lipid peroxidation.

OBJECTIVES: We aim to evaluate whether and to what extent dietary carbohydrate quality and quantity are associated with systemic levels of lipid peroxidation in females.

DESIGN: In this cross-sectional analysis of 2163 middle-aged females, a subset of the Shanghai Women’s Health Study, we measured lipid peroxidation biomarkers F2-isoprostanes (F2-IsoPs) and its metabolite 2,3-dinor-5,6-dihydro-15-F2t-IsoP (F2-IsoP-M) in urine. The quality of carbohydrate was defined by dietary GI, assessed using a validated food-frequency questionnaire via in-person interviews. A multivariable linear regression model with restricted cubic spline functions was used to evaluate the association of measured biomarkers with carbohydrate intake and dietary GI.

RESULTS: After adjustment for potential confounding factors such as cigarette smoking, BMI, comorbidities among others, we found that F2-IsoP-M concentrations were positively associated with both carbohydrate intake and dietary GI. Carbohydrate intake and dietary GI were weakly correlated (r = 0.12). When further mutually adjusted for the two factors, the positive association with F2-IsoP-M remained statistically significant for GI (P = 0.004) but not for carbohydrate intake (P = 0.50). Compared with those in the 10th percentile of dietary GI, fold-increases (95% CI) in F2-IsoP-M concentrations for those in the 30th, 50th, 70th, and 90th percentiles were 1.03 (1.00, 1.07), 1.06 (1.01, 1.10), 1.09 (1.03, 1.14), and 1.13 (1.05, 1.21), respectively. Moreover, there appeared a threshold regarding the association between dietary GI and F2-IsoP-M concentrations, with the dose-effect slope of GI being 2.3-times greater when GI ≥ 75 relative to GI < 75.

CONCLUSIONS: This study provides evidence that the quality of dietary carbohydrate may be more important than the quantity of the intake with regard to systemic lipid peroxidation.

PMID:35170729 | DOI:10.1093/ajcn/nqac047

Am J Clin Nutr. 2022 Feb 16:nqac044. doi: 10.1093/ajcn/nqac044. Online ahead of print.

ABSTRACT

BACKGROUND: Energy deficiency can result in menstrual disturbances and compromised bone health in women, a condition known as the Female Athlete Triad.

OBJECTIVE: The REFUEL randomized controlled trial assessed the impact of increased energy intake on bone health and menstrual function in exercising women with menstrual disturbances.

METHODS: Exercising women with oligo/amenorrhea were randomized to an intervention group (Oligo/Amen+Cal, n=40, 21.3±0.5 yrs, 55.0±1.0kg, 20.4±0.3 kg/m2) who increased energy intake 20-40% above baseline energy needs for 12 months or a control group (Oligo/Amen Control, n=36, 20.7±0.5 yrs, 59.1±1.3kg, 21.3±0.4 kg/m2). Energy intake and expenditure, metabolic and reproductive hormones, body composition, and areal bone mineral density (aBMD) were assessed.

RESULTS: The Oligo/Amen+Cal group improved energy status (increased body mass (2.6±0.4 kg), body mass index (0.9±0.2 kg/m2), fat mass (2.0±0.3 kg), body fat percentage (2.7±0.4%), and insulin-like growth factor 1 (37.4±14.6 ng/ml)) compared to the control group and experienced a greater likelihood of menses (p<0.05). Total body and spine aBMD remained unchanged (p>0.05). Both groups demonstrated decreased femoral neck aBMD at month 6 (-0.006 g/cm2, 95%CI: -0.011, -0.0002 time main effect p=0.043) and month 12 (-0.011 g/cm2, 95%CI: -0.021, -0.001, time main effect p=0.023). Both groups demonstrated a decrease in total hip aBMD at month 6 (-0.006 g/cm2, 95%CI: -0.011, -0.002, time main effect p=0.004).

CONCLUSIONS: Although higher dietary energy intake increased weight, body fat and menstrual frequency, bone mineral density was not improved, compared to the control group. The 12-month intervention may have been too short and the increase in energy intake (∼352 kcal/day), while sufficient to increase menstrual frequency, was insufficient to increase estrogen or improve aBMD. Future research should refine the optimal nutritional and/or pharmacological intervention(s) for the recovery of bone health in athletes and exercising women with oligo/amenorrhea. Clinical Trial Registry Number: NCT00392873 https://www.clinicaltrials.gov/ct2/show/NCT00392873.

PMID:35170727 | DOI:10.1093/ajcn/nqac044

Nurs Open. 2022 Feb 16. doi: 10.1002/nop2.1168. Online ahead of print.

ABSTRACT

AIM: The purpose of the study is to evaluate the effectiveness of sodium bicarbonate and zinc chloride mouthwashes on oral mucositis and quality of life in patients undergoing chemotherapy.

DESIGN: The present study was a randomized controlled trial study.

METHODS: One hundred forty-four patients with a cancer diagnosis were randomly assigned into three groups: sodium bicarbonate mouthwash (n = 48), zinc chloride mouthwash (n = 48) and placebo group (n = 48). The severity of mucositis and quality of life were examined blindly at the baseline and 3-week follow-up.

RESULTS: The grade of oral mucositis decreased at the end of the third weeks in the sodium bicarbonate and zinc chloride groups rather than the placebo group (p < .001). The severity of oral mucositis in the sodium bicarbonate and zinc chloride groups decreased from end of the first week until third week (p < .001). In addition, there was significant difference in the severity of oral mucositis among the groups at the end of the second (p = .014) and the third weeks (p < .001). Also, there was a statistically significant difference in quality of life scores between the sodium bicarbonate and zinc chloride mouthwash with the placebo group (p < .001).

CONCLUSION: Zinc chloride and sodium bicarbonate mouthwashes were effective in treating and reducing the severity of oral mucositis, and subsequently improving quality of life in patients with cancer under chemotherapy. Therefore, we can recommend zinc chloride and sodium bicarbonate at the beginning of chemotherapy to improve oral health and promoting quality of life in these patients.

PMID:35170247 | DOI:10.1002/nop2.1168

ESC Heart Fail. 2022 Feb 15. doi: 10.1002/ehf2.13849. Online ahead of print.

ABSTRACT

AIMS: Mitral valve transcatheter edge-to-edge repair (TEER) has been established as a suitable alternative to mitral valve surgery in patients with severe mitral regurgitation (MR) and high surgical risk. The PASCAL system represents a novel device, potentially augmenting the toolkit for TEER. The aim of this study was to assess and compare short and 1 year safety and efficacy of the PASCAL and MitraClip systems for TEER.

METHODS AND RESULTS: Procedural, short, and 1 year outcomes of a 1:2 propensity-matched cohort including 41 PASCAL and 82 MitraClip cases were investigated. Matching was based on clinical, laboratory, echocardiographic, and functional characteristics. The primary endpoints assessed were procedural success [as defined by the Mitral Valve Academy Research Consortium (MVARC)], residual MR, functional class, and a composite endpoint comprising death, heart failure hospitalization, and mitral valve re-intervention. We found for the PASCAL and the matched MitraClip cohort no significant differences in MVARC defined technical (90.2% vs. 95.1%, P = 0.44), device (90.2% vs. 89.0%, P = 1.0), or procedural (87.8% vs. 80.5%, P = 0.45) success rates. Accordingly, the overall MR reduction and improvement in New York Heart Association (NYHA) class were comparable (1 year follow-up: MR ≤ 2 95% vs. 93.6%, P = 1.0; NYHA ≤ 2 57.1% vs. 66.7%, P = 0.59). The composite outcome revealed no statistically significant difference between both devices (1 year follow-up: 31.7% vs. 37.8%, P = 0.55). Interestingly, we found at both short and 1 year follow-up a significantly higher rate of patients with none or trace MR in the PASCAL-treated cohort (short follow-up: 17.9% vs. 0%, P = 0.0081; 1 year follow-up: 25% vs. 0%, P = 0.0016). Conversely, the rate of aborted device implantations due to an elevated transmitral gradient was higher in PASCAL interventions (9.8% vs. 1.2%, P = 0.04).

CONCLUSIONS: Transcatheter edge-to-edge repair using the PASCAL or MitraClip device results in favourable and comparable outcomes regarding safety, efficacy, and clinical improvement after 1 year.

PMID:35170230 | DOI:10.1002/ehf2.13849

Clin Transl Sci. 2022 Feb 15. doi: 10.1111/cts.13209. Online ahead of print.

ABSTRACT

Selumetinib is an oral, potent, and highly selective allosteric MEK1/2 inhibitor approved for the treatment of pediatric patients (aged ≤2 years) with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. A granule formulation of selumetinib is under development to improve dosing precision for younger pediatric patients who may be unable to swallow capsules. This phase I crossover study investigated the effect of food on the pharmacokinetic (PK) properties of selumetinib capsule and granule formulations. Healthy male volunteers were randomized to receive selumetinib granules (25 mg) or capsules (50 mg [2 × 25 mg]) under fasted or fed conditions (a low-fat meal). Plasma concentrations and PK parameters were determined less than or equal to 48 h postdose. Safety and tolerability were assessed. Across 24 volunteers, selumetinib was absorbed quickly, with a time to maximum concentration (T_max ) ranging from ~1-3 h. Geometric mean ratios (90% confidence interval [CI]) for maximum plasma concentration (C_max ) in the fed versus fasted state were 0.61 (90% CI 0.51-0.72) and 0.40 (90% CI 0.33-0.48) for the granule and capsule formulations, respectively, whereas geometric mean ratios (90% CI) for area under the plasma drug concentration-time curve in the fed versus fasted state were 0.97 (90% CI 0.91-1.02) and 0.62 (90% CI 0.55-0.70), respectively. Levels of less than 10% conversion to the N-desmethyl selumetinib metabolite were observed. Selumetinib was well-tolerated, with only a few adverse events of mild intensity reported. Selumetinib administration with a low-fat meal resulted in lower C_max and longer T_max for both formulations versus fasted conditions. However, area under the curve for selumetinib granules was similar under fasted and fed conditions. Overall, these findings support further development of this formulation for pediatric patients.

PMID:35170228 | DOI:10.1111/cts.13209

Low Urin Tract Symptoms. 2022 Feb 15. doi: 10.1111/luts.12429. Online ahead of print.

ABSTRACT

OBJECTIVES: This study investigated male voiding dysfunction (VD) or lower urinary tract function in rectal cancer (RC) patients after laparoscopic or open total mesorectal excision with pelvic autonomic nerve preservation (PANP).

METHODS: One hundred and eighty-seven male RC patients admitted between January 2016 and May 2019 were enrolled in this study, 112 of whom underwent laparoscopic total mesorectal excision (LTME) and 75 underwent open total mesorectal excision (OTME). The International Prostatic Symptom Score (IPSS) was compared between the two groups.

RESULTS: The postoperative IPSS in patients with RC was elevated on day 7 and gradually decreased during the first month after surgery. Compared with the OTME group, the IPSS scores decreased less in the LTME group at week 1, and months 1 and 3 postoperatively (6.82 ± 2.13 vs 10.15 ± 3.86, 5.70 ± 2.45 vs 7.21 ± 2.0, and 5.01 ± 2.09 vs 5.75 ± 2.55, respectively; P < 0.05). The VD rate was significantly lower in the LTME group than the OTME group at 1, 2, and 3 weeks postoperatively (21.4% vs 26.8%,13.4% vs 25.3%, and 9.8% vs18.6%, respectively; P < 0.05); however, there was no major difference in the incidence of VD 6 months postoperatively between the two groups (P > 0.05). VD was more frequent in the OTME group than the LTME group 6 months postoperatively, but the difference was not statistically significant (odds ratio = 1.857, 95% CI, 0.964-3.645, P = 0.064).

CONCLUSIONS: LTME may be superior to OTME with respect to PANP of lower urinary tract function in males with RC.

PMID:35170222 | DOI:10.1111/luts.12429

Int J Rheum Dis. 2022 Feb 15. doi: 10.1111/1756-185X.14303. Online ahead of print.

ABSTRACT

AIM: To determine the prevalence and risk factors for uveitis in spondyloarthritis (SpA) patients.

METHODS: A total of 225 patients who fulfilled Assessment of Spondyloarthritis International Society classification criteria for axial and peripheral SpA were enrolled. The diagnosis of uveitis was confirmed by an ophthalmologist. From medical records and from clinical evaluation associated information like disease duration, and human leukocyte antigen B27 was collected. Relevant laboratory tests were done and disease severity was assessed using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score – erythrocyte sedimentation rate and C-reactive protein. Characteristics of uveitis positive and uveitis negative groups were compared. Multivariate logistic regression analysis was done for the risk factors, and P values <.05 were considered significant.

RESULTS: Prevalence of uveitis was 18.7%. The disease duration was 9.3 ± 7 years and 5.4 ± 4.5 years in uveitis and no uveitis groups respectively (P ≤ .001). Family history of SpA was positive in 45.2% in the uveitis group (P ≤ .001). The frequency of axial SpA was 92.9% and 73.8% in the uveitis and no uveitis groups respectively (P ≤ .008). The mean BASDAI was 2.4 ± 1.9 and 3.3 ± 2.8 in uveitis and no uveitis groups respectively (P = .050). In multivariate logistic regression analysis, among the selected variables, family history of SpA (odds ratio [OR] =3.697; 95% CI =1.616-8.457; P = .002) and duration of disease (OR =1.089; 95% CI =1.004-1.181; P = .039) were independently associated with the occurrence of uveitis.

CONCLUSIONS: The prevalence of uveitis was 18.7%. The family history and the disease duration of SpA were independently associated with uveitis.

PMID:35170215 | DOI:10.1111/1756-185X.14303

Environ Microbiol. 2022 Feb 15. doi: 10.1111/1462-2920.15919. Online ahead of print.

ABSTRACT

Botrytis cinerea is a broad-host-range necrotrophic phytopathogen responsible for serious diseases in leading crops. To facilitate infection, B. cinerea secretes a large number of effectors that induce plant cell death. In screening secretome data of B. cinerea during infection stage, we identified a phytotoxic protein (BcSSP2) that can also induce immune resistance in plants. BcSSP2 is a small, cysteine-rich protein without any known domains. Transient expression of BcSSP2 in leaves caused chlorosis that intensifies with time and eventually leads to death. Point mutations in eight of 10 cysteine residues abolished phytotoxicity, but residual toxic activity remained after heating treatment, suggesting contribution of unknown epitopes to protein phytotoxicity. The expression of bcssp2 was low during the first 36 h after inoculation and increased sharply upon transition to late infection stage. Deletion of bcssp2 did not cause statistically significant changes in lesions size on bean and tobacco leaves. Further analyses indicated that the phytotoxicity of BcSSP2 is negatively regulated by the receptor-like kinases BAK1 and SOBIR1. Collectively, our findings show that BcSSP2 is an effector protein that toxifies the host cells, but is also recognized by the plant immune system.

PMID:35170184 | DOI:10.1111/1462-2920.15919

Dermatol Ther. 2022 Feb 16:e15384. doi: 10.1111/dth.15384. Online ahead of print.

ABSTRACT

A role of human papilloma virus (HPV) vaccines as a therapy for genital warts was suggested, nevertheless; it has not been established in clinical trials and has yet to be determined. To evaluate a potential benefit of intralesional injection of bivalent HPV (Cervarix) vaccine as a treatment for anogenital warts versus topical podophyllin resin 25%. Forty four patients with anogenital warts were included in the study, 22 patients received intralesional Cervarix every 2 weeks until clearance of lesions or for a maximum of 5 sessions. The other 22 patients received topical podophyllin resin 25% twice weekly until complete resolution or for a maximum of four weeks. Follow up was done for 6 months. Dermatology life quality index (DLQI) was measured. Complete clearance of warts was achieved in 10 patients (45.5%) in Cervarix group vs 6 patients (27.3%) in Podophyllin group. The difference was statistically insignificant. No recurrence of warts was reported in Cervarix group while 2 patiens (33.3%) showed recurrence in Podophyllin group. Both treatments were well tolerated. All patients reported significant improvement of their DLQI. Intralesional Cervarix is a promising modality showing higher rates of complete response, high safety, and no recurrence. This article is protected by copyright. All rights reserved.

PMID:35170176 | DOI:10.1111/dth.15384

J Magn Reson Imaging. 2022 Feb 16. doi: 10.1002/jmri.28107. Online ahead of print.

ABSTRACT

BACKGROUND: Fast 78-second multicontrast echo-planar MRI (EPIMix) has shown good diagnostic performance for detecting infarctions at a comprehensive stroke center, but its diagnostic performance has not been evaluated in a prospective study at a primary stroke center.

PURPOSE: To prospectively determine whether EPIMix was noninferior in detecting ischemic lesions compared to routine clinical MRI.

STUDY TYPE: Prospective cohort study.

POPULATION: A total of 118 patients with acute MRI and symptoms of ischemic stroke.

FIELD STRENGTH AND SEQUENCE: A 3 T. EPIMix (echo-planar based: T1-FLAIR, T2-weighted, T2-FLAIR, T2*, DWI) and routine clinical MRI sequences (T1-weighted fast spin echo, T2-weighted PROPELLER, T2-weighted-FLAIR fast spin echo, T2* gradient echo echo-planar, and DWI spin echo echo-planar).

ASSESSMENT: Three radiologists, blinded for clinical information, assessed signs of ischemic lesions (DWI↑, ADC↓, and T2/T2-FLAIR↑) on EPIMix and routine clinical MRI, with disagreements solved in consensus with a fourth reader to establish the reference standard.

STATISTICAL TESTS: Diagnostic performance including sensitivity and specificity against the reference standard was evaluated. EPIMix sensitivity was tested for noninferiority compared to the reference standard using Nam’s restricted maximum likelihood estimation (RMLE) Score. A P-value < 0.05 was considered statistically significant.

RESULTS: Of 118 patients (mean age 62 ± 16 years, 58% males), 25% (n = 30) had MRI signs of acute infarcts. EPIMix was noninferior with 97% (95% CI 83-100) sensitivity for reader 1, 100% (95% CI 88-100) sensitivity for reader 2, and 90% (95% CI 88-98) sensitivity for reader 3 vs. 93% (95% CI 78-99) sensitivity for readers 1 and 2 and 90% (95% CI 74-98) for reader 3 on routine clinical MRI. Specificity was 99% (95% CI 94-100) for reader 1, 100% (95% CI 96-100) for reader 2, and 98% (95% CI 92-100) for reader 3 on EPIMix vs. 100% (95% CI 96-100) for all readers on routine clinical MRI.

CONCLUSION: EPIMix was noninferior to routine clinical MRI for the diagnosis of acute ischemic stroke.

EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

PMID:35170134 | DOI:10.1002/jmri.28107