Nevin Manimala

BJU Int. 2021 Sep 8. doi: 10.1111/bju.15593. Online ahead of print.

ABSTRACT

OBJECTIVE: This paper describes a novel syphoning ureteral access sheath (UAS) intended for use during flexible uretero-renoscopy (URS). We aimed to assess if in vitro it could reduce intrarenal pressure (IRP) and increase irrigation flow compared to traditional UAS.

METHODS: A validated phantom kidney with fiber optic pressure sensing capabilities was used to assess IRP. Standardized 80cm H₂ 0 irrigation via a ureterorenoscope was instilled through a traditional (11/13 Fr and 12/14 Fr) UAS and compared to the novel 11/13Fr syphoning UAS. Measured minute volume, calculated hourly flow volume and steady state IRP were compared.

RESULTS: The traditional 11/13 Fr and 12/14 Fr UAS has statistically poorer irrigation flow compared to the novel syphoning UAS of 19,3 vs 29,3ml/min (p=0.0004) and 22,7 vs 29,3ml/min (p=0.0021) respectively. The steady state IRP were 20mmHg for the traditional 11/13Fr and 13mmHg for the 12/14Fr compared to 0mmHg for the novel UAS.

CONCLUSION: The described novel UAS is different from traditional devices by incorporating a syphon mechanism. Our in vitro assessment demonstrates that the novel UAS holds clinical potential to reduce IRP while allowing a significant increase in irrigant flow compared to larger diameter traditional UAS.

PMID:34496125 | DOI:10.1111/bju.15593

Mol Nutr Food Res. 2021 Sep 8:e2100389. doi: 10.1002/mnfr.202100389. Online ahead of print.

ABSTRACT

SCOPE: The polyphenol xanthohumol (XN) improves dysfunctional glucose and lipid metabolism in diet-induced obesity animal models. Because XN changes intestinal microbiota composition, we hypothesized that XN requires the microbiota to mediate its benefits.

METHODS AND RESULTS: To test our hypothesis, we fed conventional and germ-free male Swiss Webster mice either a low-fat diet (10% fat derived calories), a high-fat diet (60% fat derived calories), or a high-fat diet supplemented with XN at 60 mg/kg body weight per day for 10 weeks, and measured parameters of glucose and lipid metabolism. In conventional mice, we discovered XN supplementation decreased plasma insulin concentrations and improved Homeostatic Model Assessment of Insulin Resistance. In germ-free mice, XN supplementation failed to improve these outcomes. Fecal sample 16S rRNA gene sequencing analysis suggested XN supplementation changes microbial composition and dramatically alters the predicted functional capacity of the intestinal microbiota. Furthermore, the intestinal microbiota metabolizes XN into bioactive compounds, including dihydroxanthohumol, an anti-obesogenic compound with improved bioavailability.

CONCLUSION: XN requires the intestinal microbiota to mediate its benefits, which involves complex diet-host-microbiota interactions with changes in both microbial composition and functional capacity. Our results warrant future metagenomic studies, which will provide insight into complex microbe-microbe interactions, and diet-host-microbiota interactions. This article is protected by copyright. All rights reserved.

PMID:34496124 | DOI:10.1002/mnfr.202100389

Pharm Stat. 2021 Sep 8. doi: 10.1002/pst.2168. Online ahead of print.

ABSTRACT

Phase II immuno-oncology clinical trials screen for efficacy an increasing number of treatments. In rare cancers, using historical control data is a pragmatic approach for speeding up clinical trials. The drop-the-losers design allows dropping off ineffective arms at interim analyses. We extended the original drop-the-losers design for a time-to-event outcome using a historical control through the one-sample log-rank statistic. Simulated trials featured three arms at the first stage, one at the second stage, nine scenarios, eight sample sizes with 5%- and 10%- nominal family-wise error rate (FWER). A numerical algorithm is provided to solve power calculations at the design stage. Our design was compared with a group of three independent single-arm trials (fixed design) with and without correction for multiplicity. Our design allowed strict control of the FWER at nominal levels while the misspecification of survival distribution and fixed design inflated the FWER up to three times the nominal level. The empirical power of our design increased with the sample size, the treatment effect and the number of effective treatments and dropped when more patients were recruited at the second stage. The fixed design with correction showed comparable power, while our design advantageously included more patients to the most promising arm. Recommendations for future applications are given. By taking advantage of the use of historical control data and a time-to-event outcome, the drop-the-losers design is a promising tool to meet the challenge of improving phase II clinical trials in immuno-oncology.

PMID:34496117 | DOI:10.1002/pst.2168

J Prosthodont. 2021 Sep 8. doi: 10.1111/jopr.13421. Online ahead of print.

ABSTRACT

PURPOSE: This study compared the clinical outcome of dental implants and their implant-supported restorations over a three year period involving patients both positive and negative for the human immunodeficiency virus.

MATERIALS AND METHODS: Twenty patients testing positive for the human immunodeficiency virus were recruited for this study. Twenty-one negative control patients were also selected, for a total of 41 patients. Diagnostic impressions were collected and cone beam computed tomography images were obtained. Implant size and positioning were planned using cone beam computed tomography software. Two stage or single surgery was performed as determined by the surgeon (periodontist). After a six month healing period, definitive impressions were fabricated using polyvinyl siloxane impression material. Implant stability quotient values were obtained at the time of surgery and placement of the restoration. Screw retained custom titanium abutments were designed, milled, and placed with 25 N·cm torque using a calibrated torque controller. Porcelain fused-to-metal complete coverage restorations were then cemented with elastomeric resin implant cement. Implants and restorations were assessed at 6 month intervals over a period of 3 years for stability, peri-implant health, and patient satisfaction.

RESULTS: Over the three year period, 25 of 42 implants placed in the negative control group were assessed, and 17 of 27 implants placed in the positive control group were evaluated. The overall patient retention rate was 77 percent. At the three year follow up, restorations examined were fully functional and causing no pain. Overall implant retention within the positive group was 96 percent. Implant retention within the negative control group was 100 percent. No differences were noted between groups for bone loss based on statistical tests.

CONCLUSION: Within the limitations of this clinical investigation, the presence of human immunodeficiency virus per se was not a contraindication to dental treatment with implant-supported restorations. This article is protected by copyright. All rights reserved.

PMID:34496113 | DOI:10.1111/jopr.13421

Clin Transplant. 2021 Sep 8:e14475. doi: 10.1111/ctr.14475. Online ahead of print.

ABSTRACT

INTRODUCTION: Transplantation of right kidneys can pose technical challenges due to the short right renal vein. Whether this results in inferior outcomes remains controversial.

METHOD: Healthcare Database Advanced Search (HDAS) was used to identify relevant studies. Two authors independently reviewed each study. Statistical analyses were performed using random effects models and results expressed as HR or relative risk (RR) with 95% confidence intervals. Subgroup analyses were performed in kidneys from deceased donors (DD) and living donors (LD).

RESULTS: 35 studies (257,429 participants) were identified. Both deceased and living donor right kidneys were at increased risk of delayed graft function (DGF; RR = 1.12[1.06-1.18] and RR = 1.33[1.21-1.46] respectively; both p<0.0001). In absolute terms, for each 100 kidney pairs of DD kidneys transplanted there are 2.72 (1.67-3.78, p<0.00001) excess episodes of DGF in right kidneys. Graft thromboses and graft loss due to technical failure was also significantly more likely in right kidneys, in both DD and LD settings. There was no evidence that laterality alters long term graft survival in LD or DD.

CONCLUSION: Right kidneys have inferior early outcomes, with higher rates of DGF, technical failure and graft thrombosis. However, these differences are small in absolute terms, and long-term graft survival is equivalent. This article is protected by copyright. All rights reserved.

PMID:34496090 | DOI:10.1111/ctr.14475

Phytother Res. 2021 Sep 8. doi: 10.1002/ptr.7259. Online ahead of print.

ABSTRACT

This study aimed to investigate the effect of nanomicelle curcumin (CUR), Nigella sativa oil (NS), and CUR and NS on the plasma levels of miR-21, miR-422a, and miR-503 expression in postmenopausal women with low bone mass density (BMD). This randomized, triple-blind, placebo-controlled clinical trial with a factorial design was conducted on 120 postmenopausal women from the integrated healthcare system, Tabriz-Iran. The BMD was determined using dual-energy X-ray absorptiometry (DEXA). Women were randomly divided into four groups of 30 participants: (a) CUR (80 mg) and placebo of NS, (b) NS (1,000 mg) and placebo of CUR, (c) CUR (80 mg) and NS (1,000 mg), and (d) both placebos (containing microcrystalline cellulose). The plasma level of miRNA-21, miRNA-422a, and miRNA-503 was determined by qRT-PCR. The expression level of miRNAs at the baseline was similar. At the end of the intervention, only the expression level of miRNA-21 changed statistically significantly between the four groups (p = .037) and between the NS and placebo groups (p = .005). Also, its expression in the two groups receiving NS (p = .037) and NS-CUR (p = .043) was significantly increased. NS and NS-CUR supplementation can increase the expression level of miRNA-21 in postmenopausal women with low bone density, and bring perspective to further studies of the target.

PMID:34496087 | DOI:10.1002/ptr.7259

Clin Oral Implants Res. 2021 Sep 8. doi: 10.1111/clr.13832. Online ahead of print.

ABSTRACT

OBJECTIVES: The primary objective of this study was to assess whether giving postoperative antibiotics to healthy patients after straightforward platform-switched implant placement would influence peri-implant crestal bone levels and postoperative morbidity after one year.

METHODS: Thirty-eight healthy individuals were recruited in this pilot, randomized, double-blinded, placebo-controlled clinical trial. The intervention group (n=18) received two grams of amoxicillin one hour before implant placement followed by a seven-day postoperative regimen (500 mg tid). The control group (n=20) took the same preoperative dose of amoxicillin and an identical placebo postoperatively. Mesial and distal peri-implant crestal bone levels were measured at baseline, four months and one year later with standardised periapical radiographs. Postoperative pain severity was assessed through self-administered questionnaires for seven days. Surgery-associated morbidities were evaluated after one, three, 16 weeks and one year. Descriptive and bivariate analyses were used.

RESULTS: Thirty-seven participants completed the trial. At the one-year follow-up, the mean combined peri-implant crestal bone changes for the intervention (n=18) and control (n=19) groups were – 0.44 ± 0.41 mm and – 0.27 ± 0.56 mm, respectively. The difference between the groups (intervention-control) for mean combined crestal bone level changes was not statistically significant. There were no significant differences in surgery-associated morbidities between the intervention and control groups. The one-year implant survival rate was 100% in both groups.

CONCLUSIONS: Study results suggest that a routine postoperative antibiotic regimen for healthy patients undergoing straightforward platform-switched implant placement might not be necessary to prevent postoperative peri-implant bone loss and complications.

PMID:34496085 | DOI:10.1111/clr.13832

Histopathology. 2021 Sep 8. doi: 10.1111/his.14562. Online ahead of print.

ABSTRACT

AIMS: The introduction of immunotherapy in head and neck squamous cell carcinoma (HNSCC) raises the need for harmonization between different types of antibodies and immunohistochemistry platforms for evaluating the expression of (Programmed death-ligand 1) PD-L1 with Combined Positive Score (CPS) in this tumor. We compare the expression of PD-L1, using the CPS and two widely used antibody (22C3 pharma Dx and SP263 assay) in a cohort of HNSCC.

METHODS AND RESULTS: We analyzed forty-three whole sections of HNSCC with two different anti-PD-L1 antibodies, 22C3 pharma Dx and SP263 assay. Results, expressed as CPS, were evaluated by ten trained pathologists and statistical analyses, including interobserver agreement, were performed. We found a very similar distribution for PD-L1 expression between 22C3 pharmaDx assay and SP263 assay in our cohort and a strong significant correlation between the two assays for all specimens (Spearman r= 0.945; p<0.0001). The interobserver reliability among pathologists for the continuous scores of CPS with ICC and the correlation between the two assays was both good. Moreover, the agreement rate between assays was high at all cut-offs and was best for the most relevant cut-off of CPS ≥1, while the kappa values were always in the range of almost perfect.

CONCLUSIONS: Two different assays (22C3 pharmaDx assay and SP263 assay) for PD-L1 in HNSCC showed high agreement. This data suggests the interchangeability of these two antibodies in the selection of patients with HNSCC for immunotherapy.

PMID:34496080 | DOI:10.1111/his.14562

Acta Paediatr. 2021 Sep 8. doi: 10.1111/apa.16099. Online ahead of print.

ABSTRACT

AIM: The aim of this cohort study was to evaluate doctor-diagnosed and self-reported asthma in young adults after early-childhood hospitalisation for wheezing.

METHODS: In this prospective controlled follow-up, questionnaires were sent to 95 subjects aged 24-28 years, who had been hospitalised for their first episodes of wheezing under 24 months of age. Fifty-eight cases and 100 controls returned the questionnaires.

RESULTS: The risk of doctor-diagnosed asthma was 2.14-fold (95% confidence interval 0.61-7.41) and the risk of self-reported asthma 2.39-fold (1.14-4.99) in cases compared to controls. The increased risk of self-reported asthma remained as statistically significant in analyses adjusted for current smoking, overweight and allergic rhinitis. Study subjects presented with wheezing symptoms, use of bronchodilators and inhaled corticosteroids, and with seasonal symptoms presumptive for allergic rhinitis during the last 12 months, more often than controls. The identification of respiratory syncytial virus or rhinovirus during hospitalisation in early childhood was not anymore associated with asthma risk in adulthood. As expected, previous asthma during early childhood was a strong risk factor for asthma in young adulthood.

CONCLUSION: In this controlled questionnaire study, early-childhood hospitalisation for lower respiratory infection with wheezing was an independently significant risk factor of asthma in young adults.

PMID:34496079 | DOI:10.1111/apa.16099

Hepatology. 2021 Sep 8. doi: 10.1002/hep.32142. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Chronic hepatitis B (CHB) affects over 290 million people globally and only 10% have been diagnosed, presenting a severe gap that must be addressed. We developed logistic regression and machine learning (random forest) models to accurately identify patients with HBV, using only easily-obtained demographic data from a population-based data set.

APPROACH & RESULTS: We identified participants with data on hepatitis B surface antigen (HBsAg), birth year, sex, race/ethnicity, and birthplace from 10 cycles of the National Health and Nutrition Examination Survey (NHANES, 1999-2018) and divided them into two cohorts: training (cycles 2, 3, 5, 6, 8, 10; n = 39,119) and validation (cycles 1, 4, 7, 9; n = 21,569). We then developed and tested our two models. The overall cohort was 49.2% male, 39.7% White, 23.2% Black, 29.6% Hispanic, and 7.5% Asian/Other, with a median birth year of 1973. In multivariable logistic regression, the following factors were associated with HBV infection: birth year 1991 or after (adjusted OR [aOR] of 0.28, P < 0.001), male sex (aOR 1.49, P = 0.0080), Black and Asian/Other vs. White (aOR 5.23 and 9.13, P < 0.001 for both), and being United States-born (vs. foreign-born) (aOR 0.14, P < 0.001). We found that the machine learning model consistently outperformed the logistic regression model, with higher AUROC values (0.83 vs. 0.75 in validation cohort, P < 0.001) and better differentiation of high and low risk individuals.

CONCLUSIONS: Our machine learning model provides a simple, targeted approach to HBV screening, using only easily-obtained demographic data.

PMID:34496066 | DOI:10.1002/hep.32142