Specific Dose Research Articles

Non-vitamin-K-antagonist oral anticoagulants (NOACs) after acute myocardial infarction: a network meta-analysis

Abstract Background Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging and the optimal antithrombotic therapy remains uncertain. The potential of NOACs to prevent ischaemic cardiovascular events is promising but evidence remains limited. Purpose To assess the efficacy and safety of NOACs in addition to background antiplatelet therapy for secondary prevention post-AMI in people without an indication for anticoagulation. Methods We performed a systematic literature search in September 2022, assessed each included RCT, extracted study data and conducted a network meta-analyses (NMA) using the R package 'netmeta'. Results We included six RCTs, with 33,039 participants. Moderate to high-certainty-evidence suggests rivaroxaban reduces all-cause mortality (RR 0.82, 95% CI 0.69 to 0.98) and probably reduces cardiovascular death (RR 0.83, 95% CI 0.69 to 1.01). Low-certainty-evidence suggests dabigatran may reduce all-cause mortality compared with placebo (RR 0.57, 95% CI 0.31 to 1.06). There is probably little or no difference in all-cause mortality (RR 1.09, 95% CI 0.88 to 1.35) and cardiovascular death (RR 0.99, 95% CI 0.77 to 1.27) between apixaban and placebo. There is uncertainty about the rate of cardiovascular death with dabigatran compared with placebo, as the point estimate might suggest benefit (RR 0.72, 95% CI 0.34 to 1.52). Moderate to high-certainty-evidence suggests that NOACs (specifically apixaban and rivaroxaban) probably increase major bleeding compared with placebo (apixaban vs placebo: RR 2.41, 95% CI 1.44 to 4.06, rivaroxaban vs placebo: RR 3.31, 95% CI 1.12 to 9.77). The evidence is uncertain about the risk of major bleeding with dabigatran (dabigatran vs placebo: RR 1.74, 95% CI 0.22 to 14.12). The results from the NMA were inconclusive between the different NOACs in all individual doses for all primary outcomes. However, low-certainty-evidence suggests that apixaban (combined dose) might not be as effective as rivaroxaban or dabigatran in preventing all-cause mortality after AMI in people without an indication for anticoagulation. Conclusions Moderate to high-certainty-evidence suggests rivaroxaban reduces all-cause mortality and probably reduces cardiovascular death after AMI. Low-certainty evidence suggests dabigatran may reduce all-cause mortality. Moderate-certainty evidence suggests no meaningful difference in the rate of all-cause mortality and cardiovascular death between apixaban and placebo. Moreover, no meaningful benefit in efficacy outcomes was detected for specific therapy doses for any of the NOACs following AMI in people without an indication for anticoagulation. Moderate to high-certainty evidence suggests that NOACs probably increase major bleeding compared with placebo. Our network meta-analysis did not show superiority of one NOAC over another for any primary outcome. Head-to-head trials, comparing NOACs against each other, are required to provide more certain evidence.

Direct oral anticoagulation versus warfarin in atrial fibrillation: a nationwide cohort study of effectiveness and safety among frail patients

Abstract Background Frail patients with atrial fibrillation carry a high risk of both stroke and treatment-related bleeding complications, but evidence for the safety and effectiveness of anticoagulation regimens in frail patients remain sparse. Objectives To determine the comparative effectiveness and safety of DOAC versus warfarin in frail patients with atrial fibrillation. Methods A nationwide registry-based cohort study applying a new-user design including all frail patients with atrial fibrillation who redeemed a prescription for DOAC or warfarin between January 2012 and December 2020. We applied inverse probability of treatment weighting (IPTW) to account for baseline confounding and applied a marginal structural modelling approach with weighted pooled regression to compute hazard ratios (HR) and risk differences for thromboembolic events and major bleeding comparing specific DOAC doses with warfarin. Results We identified 32048 anticoagulation naïve frail patients (median age 80 years, 53% female) with atrial fibrillation who started anticoagulation treatment: 6747 (21.1%) patients initiated warfarin therapy, 17076 (50.3%) initiated standard dose DOAC, and 9179 (28.6%) patients with indication for dose reduction initiated reduced dose DOAC. The median CHA2DS2-VASc score was 5. The comparative effectiveness analyses showed a similar risk for thromboembolism with weighted HRs of 0.95 (95% CI 0.80-1.13) for standard dose DOAC versus warfarin, and 0.97 (95% CI 0.77-1.23) for reduced dose DOAC versus warfarin (see Table). The thromboembolic event free survival difference at one year was -0.2% for DOAC regardless of dosing when compared with warfarin. The comparative safety analyses revealed significantly lower risk of major bleeding among patients initiating standard dose (weighted HR 0.69, 95% CI 0.59-0.87) or reduced dose DOAC (weighted HR 0.67, 95% 0.55-0.81) when compared with warfarin. The risk difference of bleeding at one year for DOAC users varied between -1.3% and -3.0%, with the greatest difference for patients with high frailty level initiating reduced dose DOAC. Conclusion We observed similar risk of thromboembolism and significantly lower risk of major bleeding associated with both standard and reduced DOAC treatment regimens compared with warfarin in frail patients with atrial fibrillation in routine clinical practice.

Transdermal patches: updated review as a novel drug delivery system

Transdermal patches are a non-invasive method of drug administration. It is an adhesive patch designed to deliver a specific dose of medication through the skin and into the bloodstream throughout the body. Transdermal drug delivery has several advantages over other routes of administration, for instance, it is less invasive, patient-friendly, and has the ability to bypass first-pass metabolism and the destructive acidic environment of the stomach that occurs upon the oral ingestion of drugs. Further offering a prolonged period of regulated medication release. The preparation procedures for various transdermal patch types, including membrane matrix, drug-in-adhesive, and micro reservoir patches, are covered in this review article. The various transdermal dosage form evaluation techniques have also been studied.

Effectiveness of alpha-lipoic acid in patients with neuropathic pain associated with type I and type II diabetes mellitus: A systematic review and meta-analysis.

This systematic review explores the most current evidence regarding the mechanisms of neuropathic pain in patients with different types of diabetes and how this pain affects different functional and structural components of the neuroanatomical pain pathways. The review also seeks to provide guidelines for the best approach and treatment for patients experiencing this type of pain. The objective is to determine the effectiveness of alpha-lipoic acid (ALA) in improving functional and symptomatic outcomes in patients with diabetes mellitus type I and type II. To determine the effectiveness of alpha-lipoic acid (ALA) in improving functional and symptomatic outcomes in patients with diabetes mellitus type I and type II. We systematically search MEDLINE (via PubMed), EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, and Web of Science databases. The findings of this review show that different forms of ALA do not present statistically significant changes for any of the scales included, including total symptom score (standardized mean difference [SMD] = -3.59, confidence interval [CI] = -4.16 to -3.02, and P < .00001), neuropathy impairment score (SMD = -1.42, CI = -3.68 to 0.84, and P = .22), and neuropathy symptom checklist (SMD = -0.09, CI = -0.15 to -0.02, and P = .01). In comparison to the use of a placebo, the findings suggest that ALA does not exhibit significant differences in terms of pain reduction and different functional scales. Moreover, no specific dosages are identified to support the use of ALA for the reduction of neuropathic pain.

Menthol Dissolved in Dimethyl Sulfoxide Protects Against Epileptiform Activity Induced by Pentylenetetrazol in Male Rats.

This research aims to investigate the protective action of menthol dissolved in dimethyl sulfoxide (DMSO) on experimental epileptiform activity induced by the intraperitoneal (IP) injection of pentylenetetrazol (PTZ) in male rats. Thirty adult male Wistar rats weighing 200-250 g were randomly assigned to five equal groups. The control animals received normal saline (200 μL) and the rest four cohorts were considered as treatment. Menthol was dissolved in DMSO and intraperitoneally injected at the doses of 100, 200, and 400 mg/kg into the first, second, and third groups (M100, M200, and M400 V=200 μL), respectively. The fourth treatment was injected with the solvent (200 μL). The animals were anesthetized, then underwent cranial surgery and a recording electrode was implanted in the stratum radiatum of the hippocampal carbonic anhydrase 1 (CA1) region (AP=-2.76 mm, ML=-1.4 mm and DV=3 mm). The seizure activity was induced by PTZ (IP) and assessed by counting and measuring amplitudes of the spikes for 10 minutes using the eTrace program. Menthol was observed to significantly reduce the activity level of PTZ-induced epileptiform activity, as well as exert a protective and inhibitory action on proconvulsant effect of DMSO in a dose-dependent manner. Menthol can potentially be used as an adjuvant to prevent seizure activity. Dimethyl sulfoxide (DMSO) induces proconvulsant effects, significantly increasing spike counts.Menthol 100 mg/kg also stimulates seizure activity, leading to a substantial spike count increase.Menthol 200 and 400 mg/kg exhibit inhibitory effects, decreasing seizure activity and spike counts. In this study, we explored the potential protective effects of menthol, dissolved in dimethyl sulfoxide (DMSO), on experimentally induced epileptiform activity in male rats. Our research involved thirty adult male Wistar rats, divided into five groups. While the control group received normal saline, the remaining four groups were treated with different doses of menthol in DMSO. The rats underwent surgery, and electrodes were implanted in the hippocampal region for recording. Using pentylenetetrazol (PTZ) to induce seizure activity, we observed that menthol, administered at varying doses, significantly reduced the level of epileptiform activity triggered by PTZ. Notably, menthol also demonstrated a protective and inhibitory effect on the proconvulsant action of DMSO, and this effect was dose-dependent. In simpler terms, our findings suggest that menthol has the potential to be used as an additional treatment to prevent seizure activity. This means that incorporating menthol, especially at specific doses, may offer a protective influence against epileptic events. This research sheds light on a promising avenue for potential therapeutic interventions, emphasizing the importance of further exploration of menthol's role in epilepsy prevention. Ultimately, our study opens the door to considering menthol as a valuable component in the development of strategies to mitigate the impact of seizures.

Yenilebilir yılan pancarı (Arum maculatum) yumru tozu enkapsülasyonu

Cuckoopint (Arum maculatum), an edible wild plant species, grows in Asia, Europe, and North Africa. The aerial parts of the plant are consumed as food. The plant's tubers are used in traditional folk medicine to treat gastrointestinal disorders. When consumed fresh, the plant's tubers have a toxic effect, and the dried form is safe if it does not exceed a certain amount. Tuber powders can also have a poisonous effect when taken in excessive amounts accidentally and unconsciously. In this study, it was investigated whether it is possible to prepare the powder obtained by drying the tubers of the edible wild plant A. maculatum by encapsulating it with chitosan, an edible, biocompatible, mucoadhesive polysaccharide, in specific doses. A. maculatum-chitosan microcapsules were prepared with A. maculatum tuber powder and chitosan. The effects of medium parameters such as pH, temperature, and ionic strength on the microcapsules' structural integrity and release properties were investigated. Encapsulation of tuber powders prepared in specific formulations into microcapsules can help prevent accidental overdose by the public. Commercial storage, transport, and marketing of cuckoopint tuber powder may be possible through encapsulation.

Detailed review on Bevacizumab and its target therapies

The review in this article focuses on bevacizumab, an agent widely used in a variety of treatment strategies. It provides an overview of the pharmacokinetics and pharmacodynamics of bevacizumab, with a focus on intravenous administration and available specific dose strengths. This article discusses treatment strategies with bevacizumab and emphasizes the importance of understanding its pharmacokinetic properties to optimize its efficacy. In addition, this review covers a wide range of side effects associated with bevacizumab, including cardiovascular, gastrointestinal, hematological, immune, musculoskeletal, nervous, renal, respiratory, and other side effects. The importance of close monitoring and prompt management of adverse events is emphasized to ensure patient safety and optimize patient outcomes. Overall, this literature review provides valuable insight into the use of bevacizumab and helps health professionals make informed decisions regarding dosing, monitoring, and management of side effects.

Intraoperative radiotherapy in breast cancer: Alterations to the tumor microenvironment and subsequent biological outcomes (Review).

Intraoperative radiotherapy (IORT) is a precise, single high‑dose irradiation directly targeting the tumor bed during surgery. In comparison with traditional external beam RT, it minimizes damage to other normal tissues, ensures an adequate dose to the tumor bed and results in improved cosmetic outcomes and quality of life. Furthermore, IORT offers a shorter treatment duration, lower economic costs and therapeutic efficacy comparable with traditional RT. However, its relatively higher local recurrence rate limits its further clinical applications. Identifying effective radiosensitizing drugs and rational RT protocols will improve its advantages. Furthermore, IORT may not only damage DNA to directly kill breast tumor cells but also alter the tumor microenvironment (TME) to exert a sustained antitumor effect. Specific doses of IORT may exert anti‑angiogenic effects, and consequently antitumor effects, by impacting post‑radiation peripheral blood levels of vascular endothelial growth factor and delta‑like 4. IORT may also modify the postoperative wound fluid composition to continuously inhibit tumor growth, e.g. by reducing components such as microRNA (miR)‑21, miR‑221, miR‑115, oncostatin M, TNF‑β, IL‑6 and IL‑8, and by elevating levels of components such as miR‑223, to inhibit the ability of postoperative wound fluid to induce proliferation, invasion and migration of residual cancer cells. IORT can also modify cancer cell glucose metabolism to inhibit the proliferation of residual tumor cells. In addition, IORT can induce a bystander effect, eliminating the postoperative wound fluid‑induced epithelial‑mesenchymal transition and tumor stem cell phenotype. Insights gained at the molecular level may provide new directions for identifying novel therapeutic targets and approaches. A more comprehensive understanding of the effects of IORT on the breast cancer (BC) TME may further its clinical application. Hence, the present article reviews the primary effects of IORT on BC and its impact on the TME, aiming to offer fresh research perspectives for relevant professionals.

Experimental study of dosimetric properties of thermoluminescent powder TLD-100

The creation of a scientifically substantiated quality assurance system for dosimetry and the optimization of medical exposure of the population of Ukraine during diagnostic and therapeutic procedures (and the possibility of dosimetric control and monitoring of emergency situations) falls within the field of the application of ionizing radiation sources (IRs). Trends in modern medicine in most countries, including Ukraine, prove a continued increase in the share of medical exposure. The main requirements and recommendations for the use of IRs for medical purposes while ensuring the radiation safety requirements for patients are provided in the documents of such International Organizations as the International Commission on Radiological Protection (ICRP), the International Atomic Energy Agency (IAEA), the World Health Organization (WHO) and the European Commission (EC).&#x0D; One of the key factors to ensure the quality of radiation therapy is metrological and dosimetric support. To enhance the effectiveness of radiation treatment and reduce the number of complications in the future, it is necessary to irradiate the local target within the patient’s body with a dose error of no more than 5%. Control of the radiation output of the therapeutic device, i.e., the calibration of the therapeutic beam used in the treatment process, is an essential element of radiation therapy.&#x0D; Radiation protection programmes are based on checking the accuracy of the calibration of remote radiotherapy devices using thermoluminescent dosimeters (TLDs) – small plastic capsules filled with thermoluminescent powder that are sent by post to radiology centres for exposure to a specific dose in a water phantom.&#x0D; Radiation therapy in Ukraine is primarily conducted using cobalt machines, X-ray therapy devices and linear accelerators.&#x0D; The results of the study include the examination of the dependency of measurement results on various exposure parameters using the automatic reader PCL-3, the determination of dosimetric characteristics of the thermoluminescent powder TLD-100, and the development of a calibration method for thermoluminescent dosimeters under standard irradiation conditions on a remote gamma therapy device.&#x0D; Therefore, the accuracy of beam calibration using TLD dosimeters has been studied, which will enable to timely detect errors in clinical dosimetry and reduce the number of cases of radiation-related complications for patients during their treatment.

Effect of St. John's Wort (Hypericum perforatum L.) on Male Sexual and Reproductive Health: A Narrative Review.

Hypericum species are widely acknowledged for their biological attributes, with notable attention being paid to Hypericum perforatum, commonly known as St. John's wort (SJW) within the Hypericum section of the Hypericaceae family. This species is among the most thoroughly investigated herbal medicines, particularly in terms of its application in the management of mild to moderate depression. SJW is used to treat depression, menopausal symptoms, attention-deficit hyperactivity disorder (ADHD), somatic symptom disorder, obsessive-compulsive disorder, and skin conditions, such as wounds and muscle pain. However, the usefulness and effectiveness of SJW for male sexual and reproductive health (SRH) are not well known. To assess the current evidence in the literature on the effect of SJW on male SRH. This narrative review followed a predetermined protocol and used MEDLINE and PubMed to identify articles published in English on the effects of SJW on male SRH. The search used various keywords, such as "Hypericum Perforatum", "St. John's Wort", and terms related to sexual and reproductive health issues. Articles published between the inception of the database and August 2023 were included. We identified 12 articles published from 1999 to 2019, the majority of which were experimental and conducted on animals. These studies demonstrate variability in terms of design, sample size, type of SJW extract used, the dosage administered, and duration of treatment. Studies have indicated potential sexual dysfunction (SD) due to SJW, which includes reduced libido, delayed ejaculation, delayed orgasm, and erectile dysfunction. Additionally, reproductive toxicity has been suggested, as evidenced by spermicidal effects through the inhibition of sperm motility, abnormal spermatozoa, chromosomal aberrations, and DNA denaturation. Furthermore, some studies have reported potential adverse events during maternal exposure, inhibition of fertilization, and disruption of reproductive parameters. Our review suggests that the safety and efficacy of SJW in the treatment of human SRH remain unclear. Further comprehensive, well-designed studies with larger samples, longer exposure periods, and specific dosages are needed to clarify SJW's effects of SJW. Therefore, consultation with healthcare professionals before using herbal remedies or supplements is crucial.

Uncertainties associated with direct thyroid measurements using an NaI(Tl) survey meter: the effect of anatomical differences among individuals.

Photon detectors utilised for direct thyroid measurements to determine the radioiodine content in the thyroid are normally calibrated using a phantom that mimics the human neck, including the thyroid. However, such measurements are necessarily subject to uncertainty because of the difference between the phantom and the real human subject and also the morphological differences among individuals. In this study, personal voxel phantoms were created from magnetic resonance images of the necks of 24 adult volunteers (15 males and 9 females), and numerical simulations using these phantoms were performed to examine the variation in a conversion factor (131I kBq in the thyroid per μSvh-1) for a conventional NaI(Tl) survey meter among the individuals and also to confirm the suitability of reference Japanese voxel phantoms as a calibration standard for such measurements. As a result, it was found that the conversion factor obtained from the reference Japanese male (female) phantom was 1.29 (1.18) times larger than the average conversion factor for the male (female) subjects, suggesting that the conversion factors of the reference Japanese adult male and female phantoms would generally overestimate the 131I thyroidal contents and that the thyroid volume would be one of the factors influencing the conversion factor. This study also revealed a wide difference in the thyroid volume among individuals, which would be of concern when performing specific dose assessments for heavily exposed persons.

Dose planning study of proton versus photon radiotherapy for head and neck squamous cell carcinoma of unknown primary in the primary and recurrent setting

Background Patients with head and neck squamous cell carcinoma of unknown primary (HNCUP) are often treated with extensive radiotherapy (RT). Frequently, the bilateral nodal clinical target volume (nCTV) and the volumes of suspected mucosal primary sites (mCTV) of the pharynx and larynx is irradiated. This treatment is effective but toxic. New data suggest that omission of the contralateral nCTV and mCTV, results in few recurrences. The present study explores photon versus proton therapy, in the primary and recurrent setting. Material and methods An analysis of twelve patients previously treated for HNCUP was performed. A fictitious recurrence was defined in patients treated for unilateral disease. Independently a volumetric arc photon plan and an intensity-modulated proton plan was made for all cases and scenarios. Results Compared to the standard bilateral treatment this study shows that limiting the target to unilateral nCTV leads to a significant decrease in dysphagia of 18% and 17% and xerostomia of 4.0% and 5% for photon and protons, respectively. Comparing photon RT directly to proton RT shows a small and often insignificant gain, using protons for both bilateral and unilateral targets. Focusing on re-irradiation, benefits from using protons in both the primary setting and at re-irradiation were limited. However, using protons for re-irradiation only leads to a decrease in the tissue volume receiving a specific dose outside the target overlapping region, e.g., V90Gymean was 31, 25, and 22 cm3 for photons-photons, photons-protons, and protons-protons, respectively. For V100Gy of the ipsilateral carotid artery, no differences were observed. Conclusion Omitting contralateral nCTV irradiation and mCTV irradiation will significantly reduce toxicity. The accumulated high dose volumes can be minimised using protons for re-irradiation. However, the use of protons for primary treatment provides limited benefit in most patients.

Novel nasal formulation of xylometazoline with hyaluronic acid: In vitro ciliary beat frequency study

Acute viral rhinosinusitis (viral ARS), or commonly referred to as the “common cold”, is caused by respiratory viruses that cause disruption of the airway epithelial barrier and mucociliary dysfunction. Treatment of ARS is mainly symptomatic, with xylometazoline, a direct-acting α-adrenoceptor agonist, commonly used as a nasal decongestant. Unfortunately, this treatment does not resolve the epithelial dysfunction observed in ARS, and its use might negatively impact the nasal mucosa causing issues such as dryness, stinging, burning, rebound congestion, as well as atrophy. In light of this, a novel nasal spray formulation containing both xylometazoline and hyaluronic acid (HA) was developed to provide a more effective and safer treatment for viral ARS. HA is a natural polysaccharide known to hydrate and moisturise the upper respiratory tract, maintain the integrity of the nasal mucosa, and promote mucociliary clearance and wound healing. To investigate the potential of this combination, this study was conducted using the nasal MucilAirTMin vitro model and high-speed phase-contrast microscopy to examine the effect of xylometazoline and HA on ciliary function by measuring ciliary beat frequency and their cytotoxicity by morphological, histological and ultrastructural analysis. This research is the first to assess the effects of a specific dose and molecular weight of HA as an active pharmaceutical ingredient in nasal spray formulations. The combination of a fast-acting decongestant and an additional active agent targeting nasal epithelial dysfunction has the potential to provide an improved, reliable and safe treatment for viral ARS, and may serve as the basis for future clinical studies.

Influence of the dose of ketamine used on schizophrenia-like symptoms in mice: A correlation study with TH, GAD67, and PPAR-γ

Schizophrenia is a chronic, debilitating mental illness that has not yet been completely understood. In this study, we aimed to investigate the effects of different doses of ketamine, a non-competitive NMDA receptor antagonist, on the positive- and negative-like symptoms of schizophrenia. We also explored whether these effects are related to changes in the immunoreactivity of GAD67, TH, and PPAR-γ in brain structures. To conduct the study, male mice received ketamine (20–40 mg/kg) or its vehicle (0.9 % NaCl) intraperitoneally for 14 consecutive days. We quantified stereotyped behavior, the time of immobility in the forced swimming test (FST), and locomotor activity after 7 or 14 days. In addition, we performed ex vivo analysis of the immunoreactivity of GAD, TH, and PPAR-γ, in brain tissues after 14 days. The results showed that ketamine administration for 14 days increased the grooming time in the nose region at all tested doses. It also increased immobility in the FST at 30 mg/kg doses and decreased the number of rearing cycles during stereotyped behavior at 40 mg/kg. These behavioral effects were not associated with changes in locomotor activity. We did not observe any significant alterations regarding the immunoreactivity of brain proteins. However, we found that GAD and TH were positively correlated with the number of rearing during the stereotyped behavior at doses of 20 and 30 mg/kg ketamine, respectively. GAD was positively correlated with the number of rearing in the open field test at a dose of 20 mg/kg. TH was inversely correlated with immobility time in the FST at a dose of 30 mg/kg. PPAR-γ was inversely correlated with the number of bouts of stereotyped behavior at a dose of 40 mg/kg of ketamine. In conclusion, the behavioral alterations induced by ketamine in positive-like symptoms were reproduced with all doses tested and appear to depend on the modulatory effects of TH, GAD, and PPAR-γ. Conversely, negative-like symptoms were associated with a specific dose of ketamine.

Does in vitro fertilization affect the hearing levels of women?

This study aimed to determine whether there is a relationship between changes in blood estrogen levels and hearing threshold levels in women undergoing in vitro fertilization (IVF). Sixty patients with normal otoscopic examination findings and scheduled for IVF treatment were included in the study. All patients underwent pure tone audiometry, tympanogram tests, and otoacoustic emission measurements (TEOAE) during IVF treatment, and estrogen levels were measured simultaneously. The patients were divided into three groups based on estrogen levels during IVF. The patients' audiological test results at the beginning and end of treatment (the 12th day) were compared between the groups. There was an increase in hearing levels on the 12th day of treatment compared to the beginning of treatment in all the study groups. This increase was significant between Group 1 and Group 2 and between Group 1 and Group 3 (p<0.05). The best hearing in audiometry was determined in the patients in Group 2. While a significant increase was observed in TEOAE (otoacoustic emission) measurements in Groups 1 and 2, a significant decrease was determined in Group 3 (p<0.05). Middle ear pressure and compliance measurements on the tympanogram tests were significantly lower in Group 3 compared to Groups 1 and 2 (p<0.05). During IVF treatment, as the estrogen level increases, it causes an increase in the level of hearing, but this increase does not continue after specific doses.

Pregnant Human Myometrial 1-41 Cell Viability Test on Vitamin D Administration

Background: Preterm labor is one of the universal causes of perinatal mortality worldwide. One of the causes of preterm labor is uterine muscle integrity problems. Some mechanistic studies show insight into vitamin D activity’s possible role in the injured muscle. This study aimed to determine whether vitamin D can increase muscle cell viability.Methods: This experimental research used human smooth muscle uterine myometrium cell line PHM1-41. The cells were cultured for 24 hours in hypoxia condition, then incubated with several doses of vitamin D. The PHM1-41 cell viability was measured using spectrophotometry.Results: The result showed that the minimum level of muscle cell viability after vitamin D incubation was with 300nM administration, and the maximum level was after 10nM (88.57%+4.48 and 96.21%+2.13 respectively).Conclusions: Vitamin D at a specific dose could improve cell availability. The optimal dose to improve cell viability was 10nM.

Tungsten-based polymer composite, a new lead-free material for efficient shielding of coupled neutron-gamma radiation fields: A FLUKA simulation study

Abstract Metal-based polymer composites, a new category of advanced materials, are advantageous for effective protection of radiation field. Recent report of fabrication of tungsten (W)-Poly methyl methacrylate (PMMA) composite microcellular foams with enhanced mechanical strength properties opens up the possibility of its use in radiation attenuation. Objective of this theoretical study is to assess the efficacy of W-based polymer composite, a new lead-free shielding material for attenuating coupled neutron-gamma radiations. Current paper utilizes open-source Monte Carlo code FLUKA to evaluate shielding efficiency of PMMA composites reinforced with varying concentration W particles. Study shows that, adding even 20 vol% of W particles can significantly improve radiation shielding ability of PMMA. Performance of analogous composition Pb-based polymer composite is also examined to demonstrate its inadequacy in radiation protection compared to W-based composite. Study reveals an interesting fact that for any shield dimension, total radiation dose follows an initial descending trend with increase in heavy metal (W/Pb) proportion up to certain optimum value where dose becomes minimum, beyond that dose increases. Optimum heavy metal concentrations are found to be 70 vol% and 30 vol% for W and Pb respectively, with minimum dose for Pb shield being two orders of higher magnitude. Study is further extended to investigate shielding efficiency of conventional double-layer laminates employing W and PMMA in both high-Z/low-Z and low-Z/high-Z configurations as well as optimum concentration of W-PMMA composite and PMMA. It is shown that among all the potential designs, newly introduced composite-based double-layer shield performs best in terms of volumetric dose while single-layer optimized composite shield offers least specific dose.

Association of Left Ventricular Myocardium Dose Exposure with Heart Failure in Lung Cancer Radiotherapy

The volume of left anterior descending (LAD) coronary artery dose receiving 15 Gy (LAD V15 Gy) has been associated with major adverse cardiac events (MACE; a composite endpoint of unstable angina, heart failure hospitalization/urgent visit, myocardial infarction, coronary revascularization, and cardiac death) and mortality in patients with locally advanced non-small cell lung cancer (LA-NSCLC) following radiotherapy (RT). With growing evidence supporting specific cardiac substructure dose exposure with distinct pathophysiologic cardiac endpoints, our objective was to assess whether RT dose to the left ventricular myocardium (LVM) was associated with the specific cardiac endpoints of heart failure (HF) vs. overall MACE. Retrospective analysis of 701 patients with LA-NSCLC treated with RT between 2003 and 2014. LAD was segmented manually, while LVM (excluding blood pool) was segmented using an open-source deep learning-based automated algorithm (TotalSegmentator; Wasserthal et al, 2022) and dosimetric parameters (mean, max, and VX Gy in 5 Gy increments) collected. HF was defined as any grade ≥3 Common Terminology Criteria for Adverse Event (CTCAE) HF or cardiomyopathy. Receiver operating curve and cut-point analyses estimating HF were performed. Fine and Gray and Cox regressions, adjusting for preexisting cardiovascular (CV) risk factors and other prognostic factors, were calculated. Of 701 patients, the median age was 65 years (interquartile range [IQR], 57-73), 51% were men. At a median follow up of 20 months (IQR, 8-45) following RT, there were 64 HF events. The median time to HF was 20 months (IQR, 9-43), with a 2-year cumulative incidence of 5.2%. The optimal cut-point for the LVM dose variable with the highest C-index predicting HF was LVM V10 Gy ≥10% (.58). By LVM V10 Gy cut point ≥10% vs <10%, the 2-year HF cumulative incidence was 7.2% vs 4.0% (p = .005). Adjusting for baseline CV risk, there was an increased risk of HF with LVM V10 Gy ≥10% (vs. <10%) (subdistribution hazard ratio [SHR] 2.81; 95% confidence interval [CI], 1.02-7.70; p = .045), but not LAD V15 Gy ≥10% (p>.3). Conversely, adjusting for baseline CV risk, there was an increased risk of MACE with LAD V15 Gy ≥10% (SHR = 19.70; 95% CI = 2.57-151.35; p = 0.004), but not LVM V10 Gy ≥10% (p>0.3). On all-cause mortality analysis, adjusting for CV and other prognostic factors, LAD V15 Gy ≥10% (HR = 1.4; 95% CI = 1.02-1.80; p = 0.036), but not LVM ≥10% (p>0.5), remained significantly associated with mortality. Left ventricular myocardium V10 ≥10%, is associated with the specific endpoint of HF, but not overall MACE, while LAD V15 ≥10% remained strongly associated with MACE and all-cause mortality, but not HF. These findings underscore the need to study the interaction between RT dose to specific substructures (i.e., myocardium) and pathophysiologically relevant cardiac endpoints (i.e., HF).

Safety of Radiation Therapy for Treatment of Malignancy in Patients with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) has been considered a relative contraindication to radiation therapy (RT) due to the potential greater risk of RT-induced toxicities, however, there is limited toxicity data using modern RT techniques. This study aims to assess toxicity outcomes in patients with IBD treated with abdominal or pelvic RT. After institutional review board approval, patients with IBD who received RT to the abdomen or pelvis were filtered from an institutional research repository and their electronic medical records were reviewed. Acute toxicity was defined as that occurring within 3 months of RT. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Univariable Cox proportional hazards regression was used to assess rates of grade ≥2 toxicity-free survival. We identified 62 patients with median age of 69 years (interquartile range [IQR] 62-77) who received RT from 2006-2022. Median follow up was 15 months (IQR 4-33). Most patients were male (42; 68%) and had a diagnosis of ulcerative colitis (44; 71%). The most common primary malignancy was colorectal/anal (26; 42%). Intensity-modulated RT (IMRT) was most frequently used (38; 61%) followed by 3-dimensional conformal RT (3D-CRT) (12; 19%) and stereotactic body RT (SBRT)/brachytherapy (12; 19%). For IMRT/3D-CRT, median dose delivered was 50 Gy (IQR 49-59) in 25 fractions (IQR 25-30), and median maximum dose (Dmax) to bowel was 48 Gy (IQR 43-52); whereas for SBRT/brachytherapy, the median dose was 32 Gy (IQR 27-40) in 3 fractions (IQR 2-5) and median bowel Dmax was 32 Gy (IQR 20-37). The median biologically effective dose delivered with an assumed alpha/beta ratio of 10 (BED10) across all RT modalities was 63 Gy (IQR 60-72). After initiation of RT, 31 patients (50%) and 14 patients (23%) experienced grade ≥2 acute and late toxicity, respectively. Thirteen patients (21%) and 7 patients (11%) experienced grade 3 acute and late toxicity, respectively. No patients experienced grade >3 toxicity. Acute toxicity resulted in interruption to RT for 5 patients (8%), 2 of which did not resume RT. Four patients (6%) required adjustment to chemotherapy or IBD medication dosage as a result of their acute toxicity. Median time from RT start to acute toxicity onset was 41 days (IQR 32-46), whereas median time to onset of late toxicity was 9 months (IQR 5-15). The most common acute and late toxicities were diarrhea (21; 34%) and bowel obstruction/perforation/fistula (4; 6%), respectively. Rates of grade ≥2 toxicity-free survival overtime were not significantly associated with IBD status (active vs quiescent), delivered BED10, or bowel Dmax BED3. In patients with IBD treated with abdominal or pelvic RT for malignancy, RT was feasible with acceptable rates of toxicity and active versus quiescent IBD status did not impact toxicity outcomes. Future research is needed to elucidate specific dose constraints when treating patients with IBD.

Comparison of Plan Quality Metrics after Left Anterior Descending Coronary Artery Sparing in VMAT Esophageal Radiotherapy

Cardiotoxicity is a significant late effect of esophageal radiotherapy (RT). Mean heart dose has been implicated with major adverse cardiac events (MACE) and emerging evidence increases MACE association with left anterior descending (LAD) coronary artery specific dose. This retrospective planning study investigates the dosimetric impact of including the LAD as an OAR-sparing objective for VMAT-based plan optimization in patients previously treated for esophageal cancers. A retrospective cohort was identified of patients who underwent neoadjuvant RT for esophageal cancers between 2017-2020 without intentional LAD sparing. Treatment planning was performed using Eclipse™ treatment planning system. Doses were calculated using Acuros® XB algorithm or anisotropic analytical algorithm with a 2-2.5mm calculation grid. For each patient, the LAD was delineated and the treated VMAT plan was re-optimized to reduce the dose to the LAD receiving 15 Gy to less than 10%, when possible. Re-plans were performed such that 95% of the PTV received the prescription dose. Institutional constraints were used to minimize the dose to the heart, lung, and spinal cord (Table 1). A paired t-test was used to compare the dose between the original VMAT plan used for treatment (Esophagus Original) against those re-optimized (Esophagus + LAD), with significance of p<0.05. A total of 19 patients were identified. Of those treated, 12 of 19 original plans (63%) exceeded the LAD constraint (V15<10%) with a mean V15 Gy of 47.1%. Plan re-optimization accounting for the LAD allowed for 66.7% (9/12) of cases to meet LAD V15 constraints. Aside from increased sparing of the mean heart dose, there were no statistically significant impacts on target coverage and OAR doses otherwise, including to that of the lung and spinal cord (Table 1). Accounting for LAD dose in treatment planning may help reduce future MACE risks. LAD dose can be significantly reduced without compromising PTV coverage or having significant effects on other OAR dose sparing.