Tag: pubmed

J Clin Oncol. 2022 Aug 12:JCO2102831. doi: 10.1200/JCO.21.02831. Online ahead of print.

ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The purpose of this update was to determine differences in patient-reported chronic toxicity and disease outcomes with intensity-modulated radiation therapy (IMRT) compared with conventional pelvic radiation. Patients with cervical and endometrial cancers who received postoperative pelvic radiation were randomly assigned to conventional radiation therapy (CRT) or IMRT. Toxicity and quality of life were assessed using Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domains, and Functional Assessment of Cancer Therapy-General. Between 2012 and 2015, 279 eligible patients were enrolled to the study with a median follow-up of 37.8 months. There were no differences in overall survival (P = .53), disease-free survival (P = .21), or locoregional failure (P = .81). One year after RT, patients in the CRT arm experienced more high-level diarrhea frequency (5.8% IMRT v 15.1% CRT, P = .042) and a greater number had to take antidiarrheal medication two or more times a day (1.2% IMRT v 8.6% CRT, P = .036). At 3 years, women in the CRT arm reported a decline in urinary function, whereas the IMRT arm continued to improve (mean change in EPIC urinary score = 0.5, standard deviation = 13.0, IMRT v -6.0, standard deviation = 14.3, CRT, P = .005). In conclusion, IMRT reduces patient-reported chronic GI and urinary toxicity with no difference in treatment efficacy at 3 years.

PMID:35960897 | DOI:10.1200/JCO.21.02831

J Clin Oncol. 2022 Aug 12:JCO2102911. doi: 10.1200/JCO.21.02911. Online ahead of print.

ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In a randomized, open-label, phase III NEJ009 study, gefitinib plus chemotherapy significantly improved progression-free survival (PFS) and overall survival (OS) compared with gefitinib-alone in patients with untreated non-small-cell lung cancer harboring mutations in epidermal growth factor receptor. Herein, we report the updated survival outcome and long-term tolerability. Patients were randomly assigned to gefitinib (gefitinib 250 mg orally, once daily) and gefitinib combined with carboplatin plus pemetrexed (GCP in a 3-week cycle for six cycles followed by concurrent gefitinib and pemetrexed maintenance) groups. At the data cutoff (May 22, 2020), GCP demonstrated significantly better PFS2 (hazard ratio, 0.77; 95% CI, 0.62 to 0.97; P = .027) than gefitinib. However, the updated median OS was 38.5 months (95% CI, 31.1 to 47.1) and 49.0 months (95% CI, 41.8 to 56.7) in the gefitinib and GCP groups, respectively (hazard ratio, 0.82; 95% CI, 0.64 to 1.06; P = .127). The OS in both groups was similar for the overall patient population. No severe adverse events occurred since the first report. This updated analysis revealed that the GCP regimen improved PFS and PFS2 with an acceptable safety profile compared with gefitinib-alone. GCP is more efficient than gefitinib monotherapy as a first-line treatment for non-small-cell lung cancer with epidermal growth factor receptor mutations.

PMID:35960896 | DOI:10.1200/JCO.21.02911

Otol Neurotol. 2022 Aug 2. doi: 10.1097/MAO.0000000000003652. Online ahead of print.

ABSTRACT

OBJECTIVE: To identify demographic and clinical features impacting initial treatment pathway for vestibular schwannoma.

STUDY DESIGN: Retrospective chart review.

SETTING: Tertiary care academic medical center.

PATIENTS: Patients diagnosed with vestibular schwannoma between 2009 and 2019.

INTERVENTIONS: Observation, stereotactic radiosurgery, or microsurgical resection.

MAIN OUTCOME MEASURES: χ2 Test, one-way analysis of variance, and multivariate logistic regression were used to correlate demographic and clinical factors with initial treatment pathway for 197 newly diagnosed vestibular schwannoma patients.

RESULTS: Among 197 patients, 93 (47%) were initially treated with observation, 60 (30%) with stereotactic radiation (Gamma Knife) and 44 (22%) with surgical resection. Age univariately had no statistically significant impact on initial pathway, but those undergoing surgery trended toward a younger demographic (49.1 yr [surgery] versus 57.2 yr [observation] versus 59.0 yr [Gamma Knife]). Men were more likely to be initially observed than women (p = 0.04). Patients initially observed were more likely to have a lower Koos classification (p < 0.001) and have better tumor-ear hearing (p = 0.03). Only 34.4% of patients living outside the local geographic region were initially observed compared with 53.0% living locally (p = 0.055). Surgeon correlated with initial treatment (p = 0.04) but did not maintain significance when adjusting for hearing level or tumor size. A multiple linear regression model found age, maximum tumor diameter, and Koos class to correlate with initial treatment pathway (p < 0.0001, r2 = 0.42).

CONCLUSION: Initial treatment pathway for newly diagnosed vestibular schwannoma is impacted by demographic factors such as age, sex, and geographic proximity to the medical center. Clinical features including hearing level and tumor size also correlated with initial treatment modality.

PMID:35960883 | DOI:10.1097/MAO.0000000000003652

J Med Chem. 2022 Aug 12. doi: 10.1021/acs.jmedchem.2c01004. Online ahead of print.

ABSTRACT

Current fragment-based drug design relies on the efficient exploration of chemical space by using structurally diverse libraries of small fragments. However, structurally dissimilar compounds can exploit the same interactions and thus be functionally similar. Using three-dimensional structures of many fragments bound to multiple targets, we examined if a better strategy for selecting fragments for screening libraries exists. We show that structurally diverse fragments can be described as functionally redundant, often making the same interactions. Ranking fragments by the number of novel interactions they made, we show that functionally diverse selections of fragments substantially increase the amount of information recovered for unseen targets compared to the amounts recovered by other methods of selection. Using these results, we design small functionally efficient libraries that can give significantly more information about new protein targets than similarly sized structurally diverse libraries. By covering more functional space, we can generate more diverse sets of drug leads.

PMID:35960886 | DOI:10.1021/acs.jmedchem.2c01004

Biomed Tech (Berl). 2022 Aug 15. doi: 10.1515/bmt-2021-0019. Online ahead of print.

ABSTRACT

Transcranial magnetic stimulation (TMS) has widespread clinical applications from diagnosis to treatment. We combined TMS with non-contact magnetic detection of TMS-evoked muscle activity in peripheral limbs to explore a new diagnostic modality that enhances the utility of TMS as a clinical tool by leveraging technological advances in magnetometry. We recorded measurements in a regular hospital room using an array of optically pumped magnetometers (OPMs) inside a portable shield that encloses only the forearm and hand of the subject. We present magnetomyograms (MMG)s of TMS-evoked movement in a human hand, together with a simultaneous surface electromyograph (EMG) data. The biomagnetic signals recorded in the MMG provides detailed spatial and temporal information that is complementary to that of the electric signal channels. Moreover, we identify features in the magnetic recording beyond that of the EMG. This system demonstrates the value of biomagnetic signals in TMS-based clinical approaches and widens its availability and practical potential.

PMID:35960879 | DOI:10.1515/bmt-2021-0019

Proc Natl Acad Sci U S A. 2022 Aug 16;119(33):e2200061119. doi: 10.1073/pnas.2200061119. Epub 2022 Aug 12.

ABSTRACT

DNA looping has emerged as a central paradigm of transcriptional regulation, as it is shared across many living systems. One core property of DNA looping-based regulation is its ability to greatly enhance repression or activation of genes with only a few copies of transcriptional regulators. However, this property based on a small number of proteins raises the question of the robustness of such a mechanism with respect to the large intracellular perturbations taking place during growth and division of the cell. Here we address the issue of sensitivity to variations of intracellular parameters of gene regulation by DNA looping. We use the lac system as a prototype to experimentally identify the key features of the robustness of DNA looping in growing Escherichia coli cells. Surprisingly, we observe time intervals of tight repression spanning across division events, which can sometimes exceed 10 generations. Remarkably, the distribution of such long time intervals exhibits memoryless statistics that is mostly insensitive to repressor concentration, cell division events, and the number of distinct loops accessible to the system. By contrast, gene regulation becomes highly sensitive to these perturbations when DNA looping is absent. Using stochastic simulations, we propose that the observed robustness to division emerges from the competition between fast, multiple rebinding events of repressors and slow initiation rate of the RNA polymerase. We argue that fast rebinding events are a direct consequence of DNA looping that ensures robust gene repression across a range of intracellular perturbations.

PMID:35960846 | DOI:10.1073/pnas.2200061119

J Womens Health (Larchmt). 2022 Aug 12. doi: 10.1089/jwh.2022.0082. Online ahead of print.

ABSTRACT

Objective: To understand the impact of von Willebrand disease (VWD) on women’s health, a retrospective cohort study was conducted using UK Clinical Practice Research Datalink (CPRD) GOLD database and Hospital Episode Statistics (HES) Admitted Patient Care data from 1988 to 2016. Materials and Methods: Hysterectomy and heavy menstrual bleeding (HMB) events were identified by recorded disease/clinical codes and compared in women with and without VWD (matched 1:10 by birth and CPRD record start years [±2 years], and general practice attended). Incidence rates and incidence rate ratios (IRR) were calculated; risks were estimated using the Kaplan-Meier method. Results: HMB was recorded after cohort entry in 388 of 1,335 women (29.1%) with VWD and 1,524 of 12,463 women (12.2%) without VWD. The cumulative incidence of HMB was higher in women with versus without VWD across all ages (p < 0.0001), and irrespective of prior HMB status (p < 0.001). Women with VWD were more likely to have HMB compared with women without VWD; IRR adjusted for age and prior HMB status was 2.74 (95% confidence interval [CI]: 2.44-3.07). Hysterectomy was recorded in 88 of 1,374 women (6.4%) with VWD and 320 of 12,791 women (2.5%) without VWD. The cumulative incidence of hysterectomy was higher for women with versus without VWD (p < 0.0001), and highest among women aged ≥30 years at cohort entry. Women with VWD aged 30 – 39 years were more likely to undergo hysterectomy than women without VWD; IRR adjusted for prior HMB was 3.58 (95% CI: 2.36 – 5.44). Conclusions: These findings highlight the substantial impact of VWD on women’s health.

PMID:35960825 | DOI:10.1089/jwh.2022.0082

J Palliat Med. 2022 Aug 12. doi: 10.1089/jpm.2022.0100. Online ahead of print.

ABSTRACT

Background: Thirty-six states, including Florida, have legalized marijuana for medical and/or recreational use, yet how it is used and perceived by persons with cancer is not well understood. Objectives: The purpose of this study was to identify patterns of use, perceived benefits, and side effects of medical marijuana (MMJ) among cancer patients in Florida. Methods: For this descriptive, cross-sectional study, anyone residing within the state of Florida who was diagnosed or treated for a malignancy within the last five years and had used MMJ was eligible. An online survey containing questions about dosing, side effects, perceived benefits, and barriers to use was used. Descriptive statistics including frequencies, percentages, means, and standard deviations were used to analyze quantitative data. Responses to open-ended questions were coded and categorized. Results: Sleep (n = 112), pain (n = 96), and anxiety (n = 82) were the most common symptoms participants used MMJ to relieve and overall felt it was highly effective. MMJ was well tolerated with a minority (10.3%) reporting any adverse effects. Cost was the most frequent barrier reported by participants (42.8%). A variety of legal, bureaucratic, and system-related barriers were described. Conclusion: Participants perceived MMJ to be helpful in alleviating cancer symptoms. They held negative perceptions of the way MMJ is implemented and integrated into their oncology treatment plan. Enhanced communication and patient/provider education on MMJ are needed to inform patient decision making.

PMID:35960820 | DOI:10.1089/jpm.2022.0100

Photobiomodul Photomed Laser Surg. 2022 Aug;40(8):554-558. doi: 10.1089/photob.2021.0156.

ABSTRACT

Objective: The aim of this study was to determine the thermal effects of diode laser irradiation on titanium implants. Methods: An implant (3.5 × 11 mm) was placed into a bovine bone block. A three-wall intrabony defect was created to simulate peri-implant defect. Two thermocouples were secured to the apical and coronal surfaces to measure temperature changes (ΔT) during irradiation. The block was placed in a 37°C water bath and at room temperature (21°C). The defect was irradiated with different diode lasers (fiber 300 μm), while the coronal part of the implant was slightly emerging from the water. While the laser tip was positioned parallel to the implant, the defect was irradiated for 30 sec at 2 W in continuous and pulsed mode. Twenty laser irradiations were performed for each laser wavelength for assessment of ΔT. The linear mixed model was used for comparative statistics. Results: The 980 nm pulsed laser resulted in the highest ΔT (°C) at the coronal (22.45 ± 2.1/14.15 ± 0.13) and apical level (5.4 ± 0.56/3.56 ± 0.35) when this laser was used in both room temperature and water bath conditions, respectively. Similarly, highest ΔT (p < 0.0001) for the 810 nm was 14.3 ± 1.6/12.51 ± 0.63 and apical 3.42 ± 0.52/2.58 ± 0.25, for the 970 nm was 13 ± 1.4/9.93 ± 0.47 and apical 2.89 ± 0.19/2.01 ± 0.19 compared to the 940 nm laser coronally 10.1 ± 0.6/9.19 ± 0.35 and apically 1.67 ± 0.34/1.80 ± 0.17. The coronal part of the implant surpassed the critical threshold of 10°C when irradiated with each of the lasers in the room temperature conditions. Conclusions: Within the limitations of the study, the 940 nm laser seems to control better the risks of overheating during implant irradiation.

PMID:35960815 | DOI:10.1089/photob.2021.0156

Photobiomodul Photomed Laser Surg. 2022 Aug;40(8):580-588. doi: 10.1089/photob.2022.0045.

ABSTRACT

Objective: The objective of this research is to assess the short-term efficacy of combined erbium-doped: yttrium aluminum and garnet (Er:YAG) and neodymium-doped: yttrium aluminum garnet (Nd:YAG) lasers for the nonsurgical treatment of periodontitis, providing a reliable basis for whether this clinical treatment can be applied in clinical practice. Materials and methods: Thirty patients with periodontitis are chosen for this study. A split-mouth design was used; the left and right quadrants of the oral cavity are randomly assigned to one treatment: combined Er:YAG laser and Nd:YAG laser treatment (laser group) or scaling and root planing (SRP) group. Data on probing depth, clinical attachment level, bleeding index, and subgingival plaque and gingival crevicular fluid samples are collected in the basement, for 1 and 3 months. The levels of red complexes in subgingival plaque and cytokines in gingival sulcus fluid were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: At 1 and 3 months of follow-up, all clinical parameters in the two groups are significantly improved; there is a statistically remarkable difference between the laser group and SRP group (p < 0.001). Matrix metalloproteinase 8 levels in the laser group are notably lower than those in the SRP group 3 months after treatment (p < 0.001). At any point in time, the levels of red complexes in the laser group showed no additional advantage over those in the SRP group (p > 0.05). Conclusions: Er:YAG laser and Nd:YAG laser combined therapy on periodontitis have advantages in controlling periodontal inflammation and improving clinical symptoms.

PMID:35960814 | DOI:10.1089/photob.2022.0045