bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a Preclinical Nurse-Nurse Communication Framework for Clinical Trial Patient-Related Safety Information
Authors: Johnson Elizabeth A. , Rainbow Jessica G. , Reed Pamela G. , Gephart Sheila M. , Carrington Jane M.
Published: February 2023

Clinical trial trials have become increasingly complex in their design and implementation. Investigational safety profiles are not easily accessed by clinical nurses and providers when trial participants present for clinical care, such as in emergency or urgent care. Wearable devices are now commonly used as bridging technologies to obtain participant data and house investigational product safety information. Clinical nurse identification and communication of safety information are critical to dissuade adverse events, patient injury, and trial withdrawal, which may occur when clinical care is misaligned to a research protocol. Based on a feasibility study and follow-up wearable device prototype study, this preclinical nurse-nurse communication framework guides clinical nurse verbal and nonverbal communication of safety-related trial information to direct patient care activities in the clinical setting. Communication and information theories are incorporated with Carrington's Nurse-to-Nurse Communication Framework to encompass key components of a clinical nurse's management of a trial participant safety event when a clinical trial wearable device is encountered during initial assessment. Use of the preclinical nurse-nurse communication framework may support clinical nurse awareness of trial-related wearable devices. The framework may further emphasize the importance of engaging with research nurses, patients, and caregivers to acquire trial safety details impacting clinical care decision-making.
Examining Engagement and Usability in an Online Discussion Platform for Older Adults
Authors: Han Soojeong , Teng Andrew K. , Lin Shih-Yin , Demiris George , Zaslavsky Oleg , Chen Annie T.
Published: February 2023

Social media may facilitate older adults' ability to engage socially and explore health information, but it can present difficulties for older adults. Therefore, it is important to explore older adults' experience of usability and user engagement. We conducted two rounds of pilot studies where we used Facebook to engage older adults. We performed a mixed-methods evaluation of user engagement and usability. A directed content analysis of qualitative data from the pilot studies was used to explore engagement and perceived usability, and the Mann-WhitneyUtest was used to examine differences in feature usage and engagement. We analyzed qualitative data from 13 participants. Qualitative data analysis yielded themes pertaining to three main domains:user engagement,usability, andusability related to aging-related changes. In terms of user engagement and usability, participants in both pilot studies reported positive feedback on felt involvement and endurability, and the second pilot group reported more positive comments regarding perceived usefulness compared with the first pilot group. There was no statistically significant difference in usage over the two studies. The findings of this study suggest opportunities to improve older adults' experience of online discussion platforms. Considering changes that improve perceived aesthetic appeal and focused attention will be helpful.
Fibroblast growth factor 5 overexpression ameliorated lipopolysaccharide-induced apoptosis of hepatocytes through regulation of the phosphoinositide-3-kinase/protein kinase B pathway
Authors: Cui Shengyu , Li Yuhua , Zhang Xutao , Wu Bing , Li Ming , Gao Jixian , Xu Lin , Xia Hao
Published: February 2023

Background:

Sepsis is a systemic inflammatory syndrome induced by several infectious agents. Multiple organs are affected by sepsis, including the liver, which plays an important role in metabolism and immune homeostasis. Fibroblast growth factors (FGFs) participate in several biological processes, although the role of FGF5 in sepsis is unclear.

Methods:

In this study, lipopolysaccharide (LPS) was administrated to mice to establish a sepsis-induced liver injury. A similar in vitro study was conducted using L-02 hepatocytes. Western blot and immunohistochemistry staining were performed to evaluate the FGF5 expression level in liver tissues and cells. Inflammatory cell infiltrations, cleaved-caspase-3 expressions, reactive oxygen species and levels of inflammatory cytokines were detected by immunofluorescence, dihydroethidium staining, and reverse transcription quantitative polymerase chain reaction analysis, respectively. Flow cytometry was used to detect the apoptosis level of cells. In addition, ribonucleic acid (RNA)-sequencing was applied to explore the possible mechanism by which FGF5 exerted effects.

Results:

LPS administration caused FGF5 down-regulation in the mouse liver as well as in L-02 hepatocytes. Additionally, with FGF5 overexpression, liver injury and the level of hepatocyte apoptosis were ameliorated. Further, RNA sequencing performed in hepatocytes revealed the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) pathway as a possible pathway regulated by FGF5. This was supported using an inhibitor of the PI3K/AKT pathway, which abrogated the protective effect of FGF5 in LPS-induced hepatocyte injury.

Conclusion:

The anti-apoptotic effect of FGF5 on hepatocytes suffering from LPS has been demonstrated and was dependent on the activation of the PI3K/AKT signaling pathway.
The Influence of Kinesiology Tape on Breathing Mechanics in College-Aged Individuals–A Randomized Trial
Authors: Lindenberg Kelly M. , Shipe Nancy K. , Kletzli Katelynn , Cannizzaro Rebecca , Timko Jonathan , Calhoun Kyla
Published: February 2023

Purpose:

Kinesiology Tape (KT) has been used to improve mobility and muscle activation. Limited research has studied its effect on respiratory function. The purpose of this study was to investigate the influence of KT on chest wall excursion (CWE) and magnitude of respiratory muscle activation.

Methods:

Ninety subjects were randomly assigned to receive KT, sham tape, or no tape around the lower thoracic region. Measures, including CWE, maximal inspiratory pressure (MIP), and surface electromyography (sEMG) of intercostal and scalene muscles, were taken during a maximal inspiratory effort before (T-B) and after (T-1) tape application. Subjects continued to wear the tape and returned 48 hours later for another set of measurements (T-2). Repeated measures Analysis of Variance and post-hoc paired t-tests were used to determine the influence of tape.

Results:

No significant differences were identified for sEMG amplitude or CWE. Maximal inspiratory pressure scores showed no significant between-group effect; however, a significant within-group effect was found. Post-hoc analyses revealed significant differences between T-B and T-2 and T-1 and T-2 for all groups.

Conclusion:

Kinesiology Tape application did not show increased muscle activation, CWE, or MIP compared with sham and control scenarios. A significant training effect for MIP was identified. Future research should investigate KT effects in other age groups or with the presence of pulmonary pathology.
Multisystem Inflammatory Syndrome
Authors: Jayaseelan Keerthana , Frishman William H.
Published: February 2023

The novel coronavirus (severe acute respiratory syndrome coronavirus-2), also referred to as coronavirus disease 2019, has caused a global pandemic that cost more than 900,000 deaths and affected nearly 80 million Americans since the start of the pandemic in early 2020. A majority of cases have primarily been reported in the adult population. Initially, lower morbidity and mortality rates were noted in children, compared with adults. However, some pediatric patients have been shown to develop a rare, but severe complication of severe acute respiratory syndrome coronavirus-2 infection, referred to as Multisystem Inflammatory Syndrome in Children. The condition has now been reported in adults as well. In this article, the origins, clinical features, pathogenesis, treatment, and latest literature on multisystem inflammatory syndrome are explored.
Aortic Valve Replacement: Is Minimally Invasive Really Better? A Contemporary Systematic Review and Meta-Analysis
Authors: EL-Andari Ryaan , Fialka Nicholas M. , Shan Shubham , White Abigail , Manikala Vinod K. , Wang Shaohua
Published: February 2023

In recent years, minimally invasive cardiac surgery has increased in prevalence. There has been significant debate regarding the optimal approach to isolated aortic valve replacement between conventional midline sternotomy and minimally invasive approaches. We performed a systematic review of the contemporary literature comparing minimally invasive to full sternotomy aortic valve replacement. PubMed and Embase were systematically searched for articles published from 2010–2021. A total of 1215 studies were screened and 45 studies (148,606 patients total) met the inclusion criteria. This study found rates of in-hospital mortality were higher with full sternotomy than ministernotomy (P = 0.02). 30-day mortality was higher with full sternotomy compared to right anterior thoracotomy (P = 0.006). Renal complications were more common with full sternotomy versus ministernotomy (P < 0.00001) and right anterior thoracotomy (P < 0.0001). Rates of wound infections were greater with full sternotomy than ministernotomy (P = 0.02) and right anterior thoracotomy (P < 0.00001). Intensive care unit length of stay (P = 0.0001) and hospital length of stay (P < 0.0001) were shorter with ministernotomy compared to full sternotomy. This review found that minimally invasive approaches to isolated aortic valve replacement result in reduced early mortality and select measures of postoperative morbidity; however, long-term mortality is not significantly different based on surgical approach. An analysis of mortality alone is not sufficient for the selection of the optimal approach to isolated aortic valve replacement. Surgeon experience, individual patient characteristics, and preference require thorough consideration, and additional studies investigating quality of life measures will be imperative in identifying the optimal approach to isolated aortic valve replacement.
Cardiovascular Manifestations of Long COVID: A Review
Authors: Krug Ethan , Geckeler Keara C. , Frishman William H.
Published: February 2023

The acute phase of severe acute respiratory syndrome coronavirus 2 [coronavirus disease (COVID)] infection has many well-documented cardiovascular manifestations, however, the long-term sequelae are less understood. In this focused review, we explore the risk factors, character, and rates of cardiovascular events in patients with Long COVID, which is defined as symptoms occurring more than 4 weeks following initial infection. Research has identified increased rates of cerebrovascular disease, dysrhythmias, ischemic and inflammatory heart disease, cardiopulmonary symptoms, and thrombotic events among those with Long COVID, though the risk rates and potential mechanisms behind each cardiovascular event vary. Finally, we discuss the current gaps in the literature as well as how COVID compares to other viral infections when it comes to causing long-term cardiovascular sequelae.
Relevance of Guy's stone score in evaluation and outcome of percutaneous nephrolithotomy
Authors: Kapoor Rohit , Mane Deepak , Jai Singh Siddharth , Satav Vikram , Sabale Vilas , Ranjan Pratyush
Published: February 2023

Objectives

This study aimed to ascertain the relevance of the Guy's stone score in the evaluation and outcome of percutaneous nephrolithotomy (PCNL).

Materials and methods

This 2-year hospital-based, prospective clinical study enrolled 100 patients who were indicated for PCNL. All patients were allocated into groups according to the Guy's stone score and were compared for factors associated with stone-free rate (SFR) and complication risk. The data were statistically analyzed using SPSS version 20.

Results

The median patient age was 40 years (range, 5–70 years). A greater portion of the patients were aged 31–40 years. A majority of the stones were solitary, found in 83% of the kidneys. Overall, 49% were grouped as Guy's stone score 1, 26% as 2, 11% as 3, and 14% as 4. The overall SFR was 97%. Furthermore, SFR was found to be 100% for Guy's stone score 1, 100% for 2, 90.91% for 3, and 85.7% for 4. Intraoperative and postoperative complication rates were found in 6% and 38% of the patients, respectively. Among postoperative complications, pain (26%) was the most frequent, followed by fever (8%), bleeding (3%), and puncture site abscess (1%).

Conclusions

Based on the study findings, Guy's stone score was efficient in predicting PCNL outcomes.
Clinical and prostate multiparametric magnetic resonance imaging findings as predictors of general and clinically significant prostate cancer risk: A retrospective single-center study
Authors: Massanova Matteo , Vere Rebecca , Robertson Sophie , Crocetto Felice , Barone Biagio , Dutto Lorenzo , Ahmad Imran , Underwood Mark , Salmond Jonathan , Patel Amit , Celentano Giuseppe , Bhatt Jaimin R.
Published: February 2023

Background

To evaluate the predictive values of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2), prostate-specific antigen (PSA) level, PSA density (PSAD), digital rectal examination findings, and prostate volume, individually and in combination, for the detection of prostate cancer (PCa) in biopsy-naive patients.

Methods

We retrospectively analyzed 630 patients who underwent transrectal systematic prostate biopsy following prostate multiparametric magnetic resonance imaging. A standard 12-core biopsy procedure was performed. Univariate and multivariate analyses were performed to determine the significant predictors of clinically significant cancer but not PCa.

Results

The median age, PSA level, and PSAD were 70 years, 8.6 ng/mL, and 0.18 ng/mL/mL, respectively. A total of 374 (59.4%) of 630 patients were biopsy-positive for PCa, and 241 (64.4%) of 374 were diagnosed with clinically significant PCa (csPCa). The PI-RADS v2 score and PSAD were independent predictors of PCa and csPCa. The PI-RADS v2 score of 5 regardless of the PSAD value, or PI-RADS v2 score of 4 plus a PSAD of <0.3 ng/mL/mL, was associated with the highest csPCa detection rate (36.1%–82.1%). Instead, the PI-RADS v2 score of <3 and PSAD of <0.3 ng/mL/mL yielded the lowest risk of csPCa.

Conclusion

The combination of the PI-RADS v2 score and PSAD could prove to be a helpful and reliable diagnostic tool before performing prostate biopsies. Patients with a PI-RADS v2 score of <3 and PSAD of <0.3 ng/mL/mL could potentially avoid a prostate biopsy.
Field Therapy for Actinic Keratosis: A Structured Review of the Literature on Efficacy, Cost, and Adherence
Authors: Lampley Nathaniel , Rigo Rachel , Schlesinger Todd , Rossi Anthony M.
Published: February 2023

BACKGROUND

Although there are evidence-based guidelines for actinic keratosis management, selecting a cost-effective field therapy is challenging because of limited studies comparing cost, efficacy, and adherence among treatments.

OBJECTIVE

To review the literature on field-directed therapies for actinic keratosis, comparing efficacy, cost, and adherence data for topical and in-office treatments.

MATERIALS AND METHODS

PubMed, Embase, Web of Science, and Google Scholar databases were searched from October 2020 to March 2021 for articles on field therapy for actinic keratosis. Total cost per regimen was estimated using wholesale acquisition cost package prices and Medicare coverage rates for May 2021. Effective cost was approximated by dividing total cost by complete response rate.

RESULTS

Efficacy data for various field therapies range widely, and long-term follow-up is limited. Cross-study comparisons are challenging because of heterogeneity of studies. Field-directed therapy with topical 5-fluorouracil and photodynamic therapy have similar effective cost. Adherence may significantly affect real-world efficacy and long-term clearance; this would favor shorter duration topical regimens or in-office procedures.

CONCLUSION

Standardization of future studies examining efficacy of field treatments for actinic keratosis will allow comparison across treatments. In-office treatments such as photodynamic therapy represent a cost-effective alternative to topical therapies with comparable efficacy.
5-(4-Hydroxy-3-dimethoxybenzylidene)-thiazolidinone improves motor functions and exerts antioxidant potential in hemiparkinsonian rats
Authors: Ren Zhili , Ding Hui , Zhou Ming , Yang Nan , Liu Yanyong , Chan Piu
Published: February 2023

Our previous study demonstrated that 5-(4-hydroxy-3-dimethoxybenzylidene)-thiazolidinone (RD-1), one of rhodamine derivatives, significantly improves motor function in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model and could minimize mitochondrial impairment, which is a potential therapeutic target to slow down the dopaminergic neurodegeneration in Parkinson’s disease. To further evaluate its therapeutic and antioxidative potential in Parkinson’s disease, the current study was designed to explore the effect of RD-1 on hemiparkinsonian rats following unilateral 6-hydroxydopamine lesions. Motor functional behavioral tests, including apomorphine-induced rotational analysis and beam walking tests, were assessed. Our results showed that oral RD-1 administration for 2 weeks alleviated beam walking disability, but not the rotational behavior. Furthermore, compared to the sham group, tyrosine hydroxylase- (TH-) positive neurons in the substantia nigra pars compacta and fibers in the striatum were significantly preserved in the RD-1 treatment group. The abnormal activities of superoxide dismutase, catalase, and glutathione peroxidase and contents of MDA were evidently ameliorated by RD-1, at least partly. We conclude that RD-1 could improve motor functions and alleviate the loss of dopaminergic expression in the nigrostriatal pathway of Parkinson’s disease rats, and the protective mechanism of RD-1 against neurodegeneration was possibly via its modulation of antioxidation.
A lifetime economic research of universal HLA-B*58:01 genotyping or febuxostat initiation therapy in Chinese gout patients with mild to moderate chronic kidney disease
Authors: Hong Yuan , Chen Xichuang , Li Zhiping , Zhang Xiaoyan , Zhou Cong , Wang Yan , Wang Guangfei , Wu Wei , Zhou Danli , feng Li Hai
Published: February 2023

Objective

To evaluate Chinese long-term economic impact of universal human leukocyte antigen B (HLA-B)*58:01 genotyping-guided urate-lowering therapy or febuxostat initiation therapy for gout patients with mild to moderate chronic kidney disease (CKD) from perspective of healthcare system.

Methods

A Markov model embedded in a decision tree was structured including four mutually exclusive health states (uncontrolled-on-therapy, controlled-on-therapy, uncontrolled-off-therapy, and death). Mainly based on Chinese real-world data, the incremental costs per quality-adjusted life years (QALYs) gained were evaluated from three groups (universal HLA-B*58:01 testing strategy, and no genotyping prior to allopurinol or febuxostat initiation therapy) at 25-year time horizon. All costs were adjusted to 2021 levels based on Chinese Consumer Price Index and were discounted by 5% annually. One-way and probability sensitivity analysis were performed.

Results

Among these three groups, universal HLA-B*58:01 genotyping was the most cost-effective strategy in base-case analysis according to Chinese average willingness-to-pay threshold of $37 654.50 per QALY. The based incremental cost-effectiveness ratio was $31784.55 per QALY, associated with 0.046 additional QALYs and $1463.81 increment costs per patient at a 25-year time horizon compared with no genotyping prior to allopurinol initiation strategy. Sensitivity analysis showed 64.3% robustness of these results.

Conclusion

From Chinese perspective of healthcare system, HLA-B*58:01 genotyping strategy was cost-effective for gout patients with mild to moderate CKD in mainland China, especially in the most developed area, such as Beijing and Shanghai. Therefore, we suggest China’s health authorities choose the genotyping strategy and make different recommendations according to the differences of local conditions.
Impact of pulmonary hypertension hemodynamic presentation on perioperative outcomes in patients undergoing elective cardiac surgery: An observational study
Authors: Wang Yi-Chia , Chen Yih-Sharng , Lin Pei-Lin , Huang Chi-Hsiang
Published: February 2023

Background

Pulmonary hypertension (PH) is classified by hemodynamic presentation into precapillary, isolated postcapillary, and combined postcapillary and precapillary PH. Whether PH type influences risk stratification in cardiac surgery remains undetermined. We aimed to evaluate the incidence of perioperative (≤30 days) morbidity and mortality in different PH population.

Methods

This was a retrospective observational study. All patients who underwent right heart catheterization between August 2015 and July 2020 were divided into the noncapillary, precapillary, isolated postcapillary, and combined postcapillary and pre capillary PH groups based on their mean pulmonary arterial pressure, pulmonary artery wedge pressure, and diastolic pressure difference preoperatively.

Results

Of the 500 patients who underwent elective cardiac surgeries, 487 were analyzed. Overall, 236 patients (48.7%) had PH, and isolated postcapillary PH was the most common presentation. Mild PH proportion was highest in the precapillary PH type (70.8%), followed by isolated postcapillary PH (46.2%), and finally combined postcapillary and precapillary PH (10.7%). Patients with PH had a greater frequency of renal insufficiency and wound infection within 30 days postoperatively. Mean pulmonary arterial pressure >25 mm Hg after cardiopulmonary bypass (CPB) was a risk factor for short-term complications. New York Heart Association Functional Class ≥II, long CPB duration, and isolated postcapillary PH or combined postcapillary and precapillary PH type are independent risk factors for short-term morbidity and mortality after elective cardiac surgery.

Conclusions

Isolated postcapillary PH and combined postcapillary and precapillary PH patients had a higher complication rate 30 days postoperatively among elective cardiac surgery patients. After CPB, mean pulmonary arterial pressure >25 mm Hg was associated with greater complication frequency.
Model-Informed Estimation of Acutely Decreased Tacrolimus Clearance and Subsequent Dose Individualization in a Pediatric Renal Transplant Patient With Posterior Reversible Encephalopathy Syndrome
Authors: Miyagawa Bradley , Lazear Danielle , Hooper David K. , Vinks Alexander A. , Mizuno Tomoyuki
Published: February 2023

Background:

Considerable interpatient and interoccasion variability has been reported in tacrolimus pharmacokinetics (PK) in the pediatric renal transplant population. This study investigated tacrolimus PK in a 2-year-old post–renal transplant patient and a known CYP3A5 expresser who developed posterior reversible encephalopathy syndrome (PRES) and had significantly elevated tacrolimus blood concentrations during tacrolimus treatment. A model-informed PK assessment was performed to assist with precision dosing. Tacrolimus clearance was evaluated both before and after the development of PRES on post-transplant day (PTD) 26.

Methods:

A retrospective chart review was conducted to gather dosing data and tacrolimus concentrations, as part of a clinical pharmacology consultation service. Individual PK parameters were estimated by Bayesian estimation using a published pediatric PK model. Oral clearance (CL/F) was estimated for 3 distinct periods—before CNS symptoms (PTD 25), during the PRES event (PTD 27–30), and after oral tacrolimus was restarted (PTD 93).

Results:

Bayesian estimation showed an estimated CL/F of 15.0 L/h in the days preceding the PRES event, compared with a population mean of 16.3 L/h (95% confidence interval 14.9–17.7 L/h) for CYP3A5 expressers of the same age and weight. Samples collected on PTD 27–30 yielded an estimated CL/F of 3.6 L/h, a reduction of 76%, coinciding with clinical confirmation of PRES and therapy discontinuation. On PTD 93, an additional assessment showed a stable CL/F value of 14.5 L/h 1 month after reinitiating tacrolimus and was used to recommend a continued maintenance dose.

Conclusions:

This is the first report to demonstrate acutely decreased tacrolimus clearance in PRES, likely caused by the downregulation of metabolizing enzymes in response to inflammatory cytokines. The results suggest the ability of model-informed Bayesian estimation to characterize an acute decline in oral tacrolimus clearance after the development of PRES and the role that PK estimation may play in supporting dose selection and individualization.
Gentamicin Administration in Dialysis Patients: Before or After Hemodialysis?
Authors: Grit Geeske F. , Toren-Wielema Martha L. , Colin Pieter J. , Touw Daan J.
Published: February 2023

Background:

Gentamicin is used to treat severe infections and has a small therapeutic window. This study aimed to optimize the dosing strategy of gentamicin in intermittently hemodialyzed patients by simulating concentration–time profiles during pre- and postdialysis dosing, based on a published pharmacokinetic model.

Methods:

Pharmacokinetic simulations were performed with virtual patients, including septic patients, who were treated with gentamicin and received weekly hemodialysis with an interval of 48 h–48 h–72 h. The following dosing regimens were simulated: for nonseptic patients, 5 mg/kg gentamicin was given 1 h or 2 h before dialysis or a starting dose of 2.5 mg/kg and a maintenance dose of 1.5 mg/kg immediately after dialysis were given; for septic patients, 6 mg/kg gentamicin was given 1 h or 2 h before dialysis or a starting dose of 3 mg/kg and a maintenance dose of 1.8 mg/kg immediately were given after dialysis. The mean maximum concentration (Cmax), area under the curve (AUC)24 h, and target attainment (TA) of pharmacodynamic targets were calculated and compared. The following targets were adopted from the literature: Cmax >8 mg/L and <20 mg/L and AUC24 h >70 mg·h/L and <120 mg·h/L.

Results:

In nonseptic patients, postdialysis dosing resulted in a TA of 35% for Cmax of >8 mg/L, 100% for <20 mg/L and AUC24 h >70 mg·h/L, and 45% for <120 mg·h/L. Dosing 2 h before dialysis resulted in a TA of 100% for Cmax of >8 mg/L, 40% for <20 mg/L, 65% for AUC24 h >70 mg·h/L, and 77% for <120 mg·h/L. Simulations of septic patients resulted in comparable outcomes with higher TAs for Cmax <20 mg/L (96%), AUC24 h >70 mg·h/L (90%), and AUC24 h <120 mg·h/L (53%) for dosing 1 h before dialysis.

Conclusions:

Postdialysis dosing resulted in a low TA of Cmax >8 mg/L; however, predialysis dosing ensured a high TA of Cmax >8 mg/L and acceptable TA of Cmax <20 mg/L, AUC24 h >70 mg·h/L, and AUC24 h <120 mg·h/L, which could increase the efficacy of gentamicin. Therefore, clinicians should consider predialysis dosing of gentamicin in patients undergoing intermittent hemodialysis.
Development and Validation of a Quantitative LC-MS/MS Method for CDK4/6 Inhibitors Palbociclib, Ribociclib, Abemaciclib, and Abemaciclib-M2 in Human Plasma
Authors: Burke Sarah M. , Kamal Mustafa , Goey Andrew K. L.
Published: February 2023

Background:

The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, palbociclib, ribociclib, and abemaciclib, are standard-of-care agents for patients with hormone receptor–positive human epidermal growth factor receptor 2–negative metastatic breast cancer. In support of therapeutic drug monitoring and clinical pharmacokinetic studies, a liquid chromatography coupled with tandem mass spectrometry assay for the simultaneous quantitation of CDK4/6 inhibitors and the major active metabolite M2 of abemaciclib in human plasma has been developed.

Methods:

Analytes were extracted from 50 μL of human plasma by precipitating proteins with methanol and then collecting the supernatant. Reversed-phase high-performance liquid chromatography was performed for analyte separation using a biphasic gradient at a flow rate of 0.25–0.5 mL/min. The total run time was 9.5 minutes. The analytes were detected using MS/MS with electrospray ionization operating in positive ion mode.

Results:

Validation according to the US Food and Drug Administration's guidance showed that the new assay produced accurate (94.7%–107%) and precise (within-run: 1.2%–8.2%; between-run: 0.6%–7.5%) measurements of all analytes over a concentration range of 5–2000 ng/mL. Overall, analyte recoveries were consistent (mean values: 110%–129%). The analytes were also stable in human plasma and the final extract under various storage conditions. Finally, the clinical applicability of the assay was confirmed by quantitation of all analytes in plasma samples obtained from patients treated with CDK4/6 inhibitors. Reproducibility of the measured analyte concentrations in study samples was confirmed successfully by incurred sample reanalysis.

Conclusions:

A sensitive liquid chromatography coupled with tandem mass spectrometry method to measure CDK4/6 inhibitors was developed and validated according to the Food and Drug Administration criteria. Quantitation of all analytes in clinical plasma samples confirmed that the assay is suitable for therapeutic drug monitoring and clinical pharmacokinetic studies of CDK4/6 inhibitors.
Menopause hormone therapy and sarcodynapenia: the Canadian Longitudinal Study on Aging
Authors: Câmara Saionara M. A. , Macêdo Pedro R. S. , Velez Maria P.
Published: February 2023

Objective

To study the association between menopause hormone therapy (MHT) and sarcodynapenia in women from the Canadian Longitudinal Study on Aging.

Methods

We conducted a cross-sectional study of 10,834 eligible postmenopausal women. The exposure was prior or current use of MHT (never, ever). Sarcopenia was defined as an appendicular lean mass less than 5.72 kg/m2 using dual-energy X-ray absorptiometry, and dynapenia as a grip strength less than 20.4 kg. Sarcodynapenia was defined as the concomitant presence of sarcopenia and dynapenia. Poisson regression analysis produced prevalence ratios (PR) for the associations between MHT use and sarcodynapenia adjusted for age at interview, education, study site, smoking, diabetes, hypertension, and body mass index. Additional analyses were conducted according to duration of MHT (5 years or less, more than 5 years), age categories (45-64 years, 65 years or older), and physical activity level as per the Physical Activity Scale for the Elderly score (less active, more active).

Results

Menopause hormone therapy was not associated with sarcodynapenia (PR, 1.10; 95% CI, 0.89-1.35). When subdivided by years of use and physical activity, relative to no MHT use, MHT use for 5 years or less was associated with a higher prevalence of sarcodynapenia among less active women (PR, 1.57; 95% CI, 1.11-2.21) and with a lower prevalence among those more active (PR, 0.60; 95% CI, 0.39-0.92). The use of MHT for more than 5 years was not associated with sarcodynapenia.

Conclusions

Menopause hormone therapy for 5 years or less is associated with a lower prevalence of sarcodynapenia among physically active women and with a higher prevalence of sarcodynapenia in those less active. Strategies to promote an active lifestyle in all postmenopausal women, including MHT users, are needed to attain benefits for musculoskeletal health.
Menopause is associated with increased prevalence of nonalcoholic fatty liver disease: a systematic review and meta-analysis
Authors: Jaroenlapnopparat Aunchalee , Charoenngam Nipith , Ponvilawan Ben , Mariano Melissa , Thongpiya Jerapas , Yingchoncharoen Pitchaporn
Published: February 2023

Importance

Data are inconsistent on whether menopause is a risk for nonalcoholic fatty liver disease (NAFLD).

Objective

Using systematic review and meta-analysis, we aimed to collect all available data to determine the association between menopause and NAFLD.

Evidence Review

Potentially eligible studies were identified from EMBASE, MEDLINE, and Web of Science databases from inception to December 2021 using a search strategy that was composed of the terms for “NAFLD” and “menopause.” Eligible study must contain two groups of participants: one group of postmenopausal women and another group of premenopausal women. Then, the study must report the association between menopause and prevalent NAFLD. We extracted such data from each study and calculated pooled odds ratio (OR) by combining effect estimates of each study using a random-effects model. Funnel plot was used to assess for the presence of publication bias.

Findings

A total of 587 articles were identified. After two rounds of independent review by two investigators, 12 cross-sectional studies fulfilled the eligibility criteria. The meta-analysis of 12 studies revealed the significant association between menopause and NAFLD with a pooled OR of 2.37 (95% CI, 1.99-2.82; I
2 = 73%). The association remained significant in a sensitivity meta-analysis of six studies that reported the association with adjustment for age and metabolic factors with a pooled OR of 2.19 (95% CI, 1.73-2.78; I
2 = 74%). The funnel plot was fairly symmetric and was not suggestive of publication bias.

Conclusions and Relevance

The meta-analysis reveals that menopausal status was associated with approximately 2.4 times higher odds of NAFLD.
Antimüllerian hormone and adiposity across midlife among women in Project Viva
Authors: Francis Ellen C. , Oken Emily , Hivert Marie-France , Rifas-Shiman Sheryl L. , Chavarro Jorge E. , Perng Wei
Published: February 2023

Objective
: This study aimed to examine the association of antimüllerian hormone (AMH) with concurrent and prospective measures of adiposity during approximately 9 years of follow-up.

Methods:
Participants were 697 parous women from the Project Viva prebirth cohort without polycystic ovarian syndrome. We measured AMH at approximately 3 years postpartum (baseline). Outcomes were weight, body mass index (BMI), and waist circumference assessed at baseline, 4, and 9 years later; % body fat was assessed by bioimpedance at the 4- and 9-year visit. We used linear mixed-effect models including all outcome time points and accounting for age across follow-up and hormonal contraception prescription. In an additional model, we further adjusted for height.

Results:
Median AMH was 1.97 ng/mL (interquartile range, 0.83-4.36 ng/mL), 29.1% had AMH <1.0 ng/mL, and mean age at AMH measurement was 36.7 years (SD, 4.9 y; range, 20-48 y). AMH was inversely associated with average weight, BMI, and waist circumference over follow-up. In age-adjusted models, women with AMH <1.0 versus ≥1.0 ng/mL were 4.92 kg (95% CI, 2.01-7.82 kg) heavier, had a 2.51 cm (95% CI, 0.12-4.89 cm) greater waist circumference, and a 1.46 kg/m2 (95% CI, 0.44-2.48 kg/m2) greater BMI across the 9 years of follow-up. Findings were similar after covariate adjustment and when AMH was modeled continuously. AMH was also inversely associated with higher fat mass %; however, the CI crossed the null.

Conclusion:
Low AMH at baseline was associated with greater adiposity concurrently and across approximately 9 years of follow-up. Whether low AMH is a useful marker of metabolic risk across midlife requires further research.
Effect of Photobiomodulation With Different Wavelengths on Radiodermatitis Treatment
Authors: Camargo Cristina Pires , Forner-Cordero Arturo , Silva Bruna Matsumoto , de Souza Vinícius Melo , Cunha Higor Souza , de Oliveira Feitosa Yasmin , Campello Guilherme Arellano , dos Santos Pedro Henrique Gianjoppe , Rego Carolina Logo , Carvalho Heloisa , Gemperli Rolf
Published: February 2023

Background:

Approximately 80% of patients submitted to radiotherapy develop radiodermatitis. Photobiomodulation based on light-emitted diode (LED) is one of the therapeutic strategies for treating inflammation. This study aimed to investigate the effect of the photobiomodulation with two wavelengths, in an acute radiodermatitis animal model.

Methods:

Twenty rats were submitted to one radiotherapy session. After 15 days, the rats that developed radiodermatitis were divided into control groups, LED-630 nm, LED-850 nm, and LED-630 + 850 nm. The treatment regimen was one session lasting 10 minutes on alternate days for 21 days. We analyzed macroscopy aspects (RTOG scale), vascular density, dermal appendages, VEGF-a, TNF-alpha, MMP-9, and MMP-9 genic expression level.

Results:

All LED groups revealed a two-point reduction on the radiodermatitis severity grade compared with the baseline classification. Dermal appendage and vascular analysis showed a higher counting in all LED groups compared to control. This study showed dermal appendages twice in the 630/850 nm group compared with the control group. The 630/850 nm group showed six times more arterioles than the control group. Regarding genic expression, this study showed a 10-fold decrease between LED-630 nm versus LED-630 + 850 nm (P = 0.02) interleukin-10 expression and a 12-fold decrease between control versus LED-630 nm (P = 0.006) and LED-850 nm (P = 0.002) in TNF-alpha.

Conclusion:

LED (630 nm, 850 nm, and 630 nm + 850 nm) showed benefit in the treatment of radiodermatitis, and the association of the 630 nm + 850 nm and 630 nm parameters demonstrated the best macroscopic and microscopic results.
A Case of Super-giant Basal Cell Carcinoma Initially Diagnosed as Multiple Traumas
Authors: Okano Junko , Arata Jun , Arakawa Atsuhiro , Ogino Shuichi , Yamashita Teruyo
Published: February 2023

Basal cell carcinoma (BCC), which is relatively easy to diagnose in a clinical setting, is the most common malignant tumor in the skin. Conversely, a giant BCC, a tumor beyond 5 cm in diameter, is a rare disease. In particular, a giant BCC beyond 20 cm in diameter is called a super-giant BCC, which frequently invades into deeper tissues, including the dermis, bones, or muscles. Here, we present a case of a 71-year-old patient who was initially diagnosed with multiple traumas with a large periosteal defect of the head. The ulcer was surrounded by malodorous necrotic tissue and slough, and several bacteria that caused necrotizing fasciitis were detected. Mapping biopsies after extensive debridement yielded BCC, and therefore, he was finally diagnosed with a super-giant BCC. A careful consultation revealed a history of ulcer on the head after a head injury approximately 10 years ago. He underwent radical dissection including the external table of the skull, followed by a free latissimus dorsi muscle flap with a meshed split-thickness skin graft. Because of the slow and chronic development of a super-giant BCC, accurate diagnosis is often difficult. Careful attention should be paid in patients with long-sustained ulcers.
Biomechanics models predict increasing smooth muscle tone as a novel therapeutic target for central arterial dysfunction in hypertension
Authors: Pewowaruk Ryan J. , Colebank Mitchel J. , Spronck Bart , Korcarz Claudia E. , Gepner Adam D.
Published: February 2023

Introduction:

Vasodilation can paradoxically increase arterial stiffness in older, hypertensive adults. This study modeled increasing smooth muscle tone as a therapeutic strategy to improve central arterial dysfunction in hypertension using participant-specific simulations.

Methods:

Participant-specific models of the carotid artery were parameterized from vascular ultrasound measures of nitroglycerin-induced vasodilation in 18 hypertensive veterans. The acute changes in carotid artery mechanics were simulated for changes of ±2, ±4, and ±6% in smooth muscle tone and ±5, ±10, and ±15 mmHg in mean arterial pressure (MAP). The chronic carotid artery adaptations were simulated based on the hypothesis that the carotid artery will remodel wall-cross sectional area to maintain mechanical homeostasis.

Results:

A 6% increase in smooth muscle tone acutely decreased carotid pulse wave velocity from 6.89 ± 1.24 m/s to 5.83 ± 1.73 m/s, and a 15 mmHg decrease in MAP decreased carotid pulse wave velocity to 6.17 ± 1.23 m/s. A 6% increase in smooth muscle tone acutely decreased wall stress from 76.2 ± 12.3 to 64.2 ± 10.4 kPa, and a 15 mmHg decrease in MAP decreased wall stress to 60.6 ± 10.7 kPa. A 6% increase in smooth muscle tone chronically decreased wall cross-sectional area from 18.3 ± 5.4 to 15.2 ± 4.9 mm2, and a 15 mmHg decrease in MAP decreased wall cross-sectional area to 14.3 ± 4.6 mm2.

Conclusion:

In participant-specific simulation, increasing smooth muscle tone can have a stronger or equivalent effect on carotid artery mechanics compared with decreasing blood pressure. Increasing central arterial smooth muscle tone may be a novel therapeutic target to improve central arterial dysfunction in older, hypertensive adults and should be a focus of future research.
Factors affecting collaboration between clinical and community service organizations
Authors: Kerrissey Michaela J. , Singer Sara J.
Published: February 2023

Background

Collaboration between clinical and community-based social service organizations is increasingly seen as vital for preventing and managing chronic diseases but has been challenging to establish and sustain.

Purpose

The aim of this study was to identify organizational barriers and facilitators for clinic–community collaboration.

Methodology/Approach

We employed multiple methods to study a national sample of nonprofit community-based organizations that each collaborated with local clinical organizations for diabetes prevention in the United States. We used qualitative data collected longitudinally through 65 semistructured interviews from 2016 to 2017 at seven of these organizations and their clinical collaborators to understand their relationships. We employed survey data (N = 247 with 73% response rate) to measure and explore relationships among qualitatively identified themes and collaboration performance.

Results

We documented three levels of organizational challenges to community–clinic collaboration. Interorganizational challenges pertain to facing only weakly aligned interests across organizations. Interpersonal challenges pertain to misperceptions and miscommunications that occur as frontline employees from differing organizations seek to work together. Task-related challenges pertain to the inadequacy of current processes to effectively link services across clinical and community settings. We found that bridging leadership, provisional teamwork, and learning processes helped to overcome these challenges by enabling iterative progress. Follow-up national survey results indicated that these facilitators were significantly associated with collaboration performance.

Conclusions

Because community–clinic collaboration presents substantial interorganizational, interpersonal, and task-related challenges, financial incentives alone are likely insufficient for success.

Practice Implications

Resources that help develop capacity to work across community and clinical settings may be vital and warrant dedicated funding.
POSTERIOR SCLERAL INDENTATION IN LONG AXIAL LENGTH EYES (AXIAL LENGTH MORE THAN 34 mm) TO ASSIST IN PARS PLANA VITRECTOMY AND INTERNAL LIMITING MEMBRANE PEELING IN FULL-THICKNESS MACULAR HOLES
Authors: Al Sabti Khalid , Raizada Seemant
Published: February 2023

Purpose:

To assess a novel surgical technique to perform macular surgery in high myopic eyes, with axial lengths >34 mm, where standard-size intravitreal surgical instruments cannot reach the retinal surface during pars plana vitrectomy for internal limiting membrane peeling in myopic macular holes.

Methods:

Five eyes with axial length >34 mm were included in this study. A 7-mm Helvoston retractor was placed under Tenon capsule and guided along the eyeball until an elevation was noticed on the macular area. This elevation shortened the operating distance, temporarily, between the sclerotomy and retinal surface, enabling the use of standard-size intraocular instruments. Preoperative vision and optical coherence tomography were compared with postoperative data and used as markers of anatomical and functional success.

Results:

Vision improvement and anatomical closure of the macular hole with reattachment of the retina was achieved in all five eyes. No surgical complications associated with this surgical technique were noticed.

Conclusion:

Indenting the macular area from behind the eye globe with a 7-mm Helvoston retractor in a high myopic eye with axial length >34 mm during pars plana vitrectomy is safe and makes surgical procedures, such as internal limiting membrane removal, easier.
LONG-TERM MORPHOLOGIC CHANGES IN MACULAR NEOVASCULARIZATION UNDER AFLIBERCEPT TREATMENT WITH A TREAT-AND-EXTEND REGIMEN
Authors: Nakano Yuyako , Takeuchi Jun , Horiguchi Etsuyo , Ota Hikaru , Taki Yosuke , Ito Yasuki , Terasaki Hiroko , Nishiguchi Koji M. , Kataoka Keiko
Published: February 2023

Purpose:

To examine the morphologic changes in macular neovascularization (MNV) secondary to age-related macular degeneration after 2 years of aflibercept treatment under a treat-and-extend (T&E) regimen.

Methods:

This retrospective study analyzed the medical records for 26 eyes of 25 patients diagnosed with treatment-naive neovascular age-related macular degeneration and treated with aflibercept under a treat-and-extend regimen for 2 years. The areas of the MNV and vascular structures were assessed using swept-source optical coherence tomography angiography at baseline and after 2 years of treatment.

Results:

The mean MNV area increased significantly from 0.65 ± 0.42 mm2 at baseline to 0.78 ± 0.45 mm2 at 2 years. At 2 years, the mean change in the MNV area from baseline was 22% (interquartile range: 4%–60%). The baseline MNV area was negatively correlated with the change ratio of the MNV areas at 2 years and baseline (R = −0.68, P < 0.001). Nine of the 26 eyes (34.6%) showed newly formed mature vessels, and 7 eyes (26.9%) showed prominently developing preexisting mature vessels.

Conclusion:

Macular neovascularization expanded and showed vascular maturation under aflibercept treatment with a treat-and-extend regimen. The smaller the MNV at baseline, the greater is its expansion in 2 years.
BIOMARKERS OF MATERNAL SMOKING AND THE RISK OF RETINOBLASTOMA IN OFFSPRING
Authors: He Di , Huang Xiwen , Uppal Karan , Coleman Anne L. , Walker Douglas D. , Ritz Beate , Jones Dean P. , Heck Julia E.
Published: February 2023

Purpose:

Previous studies examining the risk of retinoblastoma with maternal smoking were inconclusive, likely due in part to the reliance on self-reported maternal smoking. This study uses biomarkers of tobacco smoking in neonatal dried blood spots to investigate associations between maternal smoking and retinoblastoma in offspring.

Methods:

The authors randomly selected 498 retinoblastoma cases and 895 control subjects born between 1983 and 2011 from a population-based case–control study in California. Maternal pregnancy-related smoking was measured using the following three metrics: provider or self-reported smoking during pregnancy, cotinine, and hydroxycotinine in neonatal blood. The authors used multivariable logistic regression to estimate the effects of maternal tobacco smoking on retinoblastoma.

Results:

Using all metrics (biomarkers or self-report), maternal smoking late in pregnancy or early postpartum was related to retinoblastoma (all types; odds ratio = 1.44, 95% confidence interval: 1.00–2.09). Relying on cotinine or hydroxycotinine to ascertain smoking, maternal smoking was related to unilateral retinoblastoma (odds ratio = 1.66, 95% confidence interval: 1.08–2.57).

Conclusion:

The results indicate that maternal smoking during pregnancy may be a risk factor for retinoblastoma, particularly among unilateral cases.