bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Summary:
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.