Single Grade Research Articles

Safety and efficacy of short percutaneous fixation in AO3 and AO4 lumbar fractures: a single-centre experience of 35 cases.

Spinal fractures with subsequent bone fragment dislocation are among the injuries most feared by patients and physicians. The surgical strategy is tailored to the individual patient's characteristics and often consists of pedicle instrumentation with rod-screw systems. Short instrumentation has been associated with worse spinal correction and increased complications. However, recent studies have suggested similar results in terms of kyphosis correction and the maintenance of sagittal alignment compared to longer instrumentation. This single-center retrospective study was conducted between January 2018 and April 2021. We included 35 single lumbar burst fractures AO Spine grade A3 or A4 with evidence of intra-canal fragments. Patients underwent minimally invasive percutaneous posterior lumbar instrumentation with pedicle screws. Patients received short segmental fixation involving only one level above and below the fractured vertebra. An immediate postoperative computed tomography (CT) scan demonstrated a significant reduction in vertebral kyphotic deformation (11.7° ± 1.6 vs 16.7° ± 5, p<0.001) and sagittal Cobb angle (9.8° ± 1.3 vs 11.7° ± 1.5, p < 0.001). The correction was slightly reduced but remained significant at 12 months for both kyphotic (12.3° ± 1.4, p = 0.03) and sagittal Cobb (10.3° ± 0.9, p = 0.04). Upper lumbar vertebrae showed even larger correction indices compared to lower lumbar segments. No implant failure or screws pullout was seen at the last follow-up. Short spinal fixation is a safe and effective treatment of complete and incomplete burst fractures with posterior bone fragment dislocation. All included patients fared well and achieved good kyphotic correction with no perioperative or long-term complications.

High-throughput Identification of Fusarium Head Blight Resistance in Wheat Varieties Using Field Robot-Assisted Imaging and Deep Learning Techniques

Fusarium head blight (FHB) has attracted much attention in food science and agriculture for its threat to wheat yields and food safety, due to the production of mycotoxins like deoxynivalenol (DON). Breeding of wheat varieties with improved FHB resistance is essential for controlling this disease. However, identifying resistance in different materials during variety selection remains time-consuming and labor-intensive. Therefore, this paper proposed a high-throughput method for the evaluation of FHB disease symptoms. It enabled the semiautomatic acquisition of images of individual wheat ears in a field environment with the aid of a field robot. The images obtained were semantically segmented to get a single wheat ear, from which the infected spikelets (ISs) were extracted, and then the disease degree was calculated. The results showed that the accuracy value of the individual wheat ear using DeepLabV3+ reached 0.996. The accuracy value of ISs was over 0.98. The mean Accuracy of this method for identifying the resistance of varieties was 0.967, and the precision of a single severity grade reached 0.980. The results indicate that the proposed method enables the acquisition and extraction of disease phenotype and rapid identification of resistance to FHB. The study also provides a reference for accurately identifying phenotypes of wheat ears in other field environments and for selecting and breeding other fungal-toxin-resistant varieties.

Adjuvant intravesical therapy in intermediate-risk non-muscle-invasive bladder cancer.

To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.

Feasibility of interdisciplinary evaluation in non-arthritic hip pain: A randomized trial

BackgroundPhysical therapy and orthopaedic surgery are two common treatments for non-arthritic hip pain. Interdisciplinary evaluation across these disciplines may produce a more supportive treatment-planning process; however, the feasibility of such an evaluation remains unknown. Hypothesis ObjectiveTo assess the feasibility of an interdisciplinary evaluation with an orthopaedic surgeon and physical therapist for non-arthritic hip pain. Study designObservational feasibility study of a randomized controlled trial. MethodsParticipants were randomized to an interdisciplinary (surgeon + physical therapist) or standard (surgeon) evaluation in a hip preservation clinic. Recruitment rate was recorded. Retention rate was calculated for all variables of interest. Enrollment and refusal reasons were recorded as patient quotes and categorized by a single grader. Time spent in clinic was compared across groups using Mann Whitney U tests (P ≤ 0.05). Study clinicians were interviewed, and responses were categorized based on pre-determined themes. ResultsEighty-one percent of eligible patients enrolled over a 15-month recruitment period. Willingness(n = 16), urgency to resolve pain(n = 10), financial compensation(n = 1), interest in research(n = 42), physical therapy(n = 6), or multiple-provider care(n = 15) were participants’ enrollment reasons; reason was not recorded for 22 participants. Time(n = 11), preference for single-provider care(n = 6), current physical therapy treatment(n = 1), and disinterest in physical therapy(n = 7) or research(n = 2) were refusal reasons of patients who did not enroll. Retention for primary variables of interest was 100% in both groups. Participants spent, on average, 23.5 min more time in clinic for the interdisciplinary evaluation compared to the standard (P < 0.001). ConclusionsAn interdisciplinary evaluation for patients with non-arthritic hip pain that included a physical therapist and orthopaedic surgeon in a hip preservation clinic was feasible and may better inform the treatment planning process.

Does the single tuition fee affect students' academic performance? Evidence from Indonesia

The rise in tuition fees has become a prominent issue in Indonesian education, especially as of 2024. It is still a concern whether the increase in UKT has a relationship with student achievement. This study aimed to determine the differences in student academic achievement based on the single tuition fee (UKT) category and the impact of UKT on student academic achievement. The sample in the study comprised 3643 samples of data on single tuition fees and student cumulative grade point averages from 2021 to 2023. Employing one sample test, ANOVA test, and linear regression analysis, the results showed that students across all UKT categories, from UKT 1 to UKT 6, surpassed the quality target standard GPA of 3.60 at UIN Raden Mas Said Surakarta. Second, the average GPA varied significantly across each category, indicating differing academic achievements among the UKT categories. Third, the UKT categories ranked from the highest to lowest score value are UKT Category 6, UKT Category 2, UKT Category 3, UKT Category 1, UKT Category 4, and UKT Category 5. Fourth, the study reveals that UKT does not impact the academic performance of students at UIN Raden Mas Said Surakarta, suggesting that other external factors not included in the study variables influence student academic achievement. Thus, increasing or decreasing UKT does not affect students’ academic achievement; instead, other external factors play a significant role in this.

Optimization of cut-off grades and depletion rates by means of dynamic programming

The determination of cut-off grades is critical for mine appraisal. Because of the time value of money, an optimum schedule of cut-off grades must be used instead of determination of a single cut-off grade for the life of a mine. In order to achieve the maximum net present value, a decreasing order of cut-off grades schedule must be used because of the opportunity cost. In the optimization of cut-off grades by dynamic programming, the depletion rates to be searched are actually limiting the search area. The optimum can be found from among the alternative depletion rates. Selling prices of mining products are volatile and future values cannot be known. This paper describes the use of dynamic programming in cut-off grades optimization and further extension of the method to price volatility in selling prices of mining products. The author introduces the general background of use of dynamic programming in cut-off grades optimization and the case in uncertain market conditions. Software developed in this subject handles to find the optimum sequence of cut-off grades and depletion rates for mineral deposits under market uncertainty. Dynamic programming method can be used as a means of cut-off grades optimization in this context very robustly.

A first-in-human, phase 1, dose escalation study of SGR-2921 as monotherapy in patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.

TPS6590 Background: Cell division cycle 7-related protein kinase (CDC7) is a cell cycle kinase that maintains DNA replication by phosphorylation and activation of the minichromosome maintenance protein 2 and 4 (MCMs), components of the replicative DNA helicase. Due to the CDC7's central role in maintaining replication fork integrity, chemical inhibition of CDC7 can ultimately lead to cancer cell death. SGR-2921 is an oral, small molecule inhibitor of CDC7. Preclinical studies demonstrate that SGR-2921 has potent anti-proliferative activity in AML cell lines representative of difficult to treat patient populations, agnostic of serious mutations (including those with p53 mutations), BTK resistance, and multiple prior lines of treatment. This anti-tumor activity has also been demonstrated in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) AML models. Methods: This is a phase 1, FIH, open-label, single-agent, two-arm, dose escalation study (NCT#05961839) designed to evaluate safety and tolerability and identify the recommended phase 2 dose (RP2D) of SGR-2921 as monotherapy in subjects with relapsed or refractory (R/R) AML, high risk (HR) MDS, or very high risk (VHR) MDS. The study utilizes an accelerated titration design with single patient cohorts that transitions to a 3+3 design once a single Grade 2 event is observed. This is a multicenter global study (US, Spain and France). SGR-2921 will be administered orally, once daily, utilizing a 5-day on and 9-day off dosing schedule over a 28-day cycle. A maximum of 144 patients will be enrolled into dose escalation and exploratory cohorts. To evaluate the effect of CYP3A4 inhibition on SGR-2921 exposure, subjects will be enrolled into one of two staggered, parallel study treatment arms, according to concomitant administration with (Arm B) or without (Arm A) azole antifungals that are strong CYP3A4 inhibitors. A single dose PK run-in will be required for subjects enrolled into the first 3 cohorts of each treatment arm. Subjects will be treated at increasing doses of SGR-2921 until the maximum tolerated dose (MTD) is exceeded. A RP2D will be selected from one of the tolerable dose levels. Key study inclusion criteria include: Age ≥ 18 years of age; Life expectancy ≥ 8 weeks; Confirmed diagnosis of R/R AML or HR and VHR MDS; Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Key study exclusion criteria include: Active malignancies not related to AML or MDS within two years prior to the first dose or requiring ongoing treatment; active CNS leukemia; QTcF ≥470 msec. The primary objectives are to evaluate the safety and tolerability of SGR-2921 as monotherapy and to identify the RP2D. Secondary objectives include evaluating SGR-2921 pharmacokinetics and investigating preliminary antitumor activity. Clinical trial information: NCT05961839 .

Is human perception reliable? Toward illumination robust food freshness prediction from food appearance — Taking lettuce freshness evaluation as an example

Machine vision-based food quality evaluation systems have achieved great attention in industry and academia in recent years because of their high-throughput and non-invasive properties. In practice, the environmental illumination conditions variations would cause visual evaluation bias for both human and machine perceptions. Compared to other existing studies which take sample images and human visual grading under fixed illumination conditions, this study first investigated the environmental illumination effects on the performance of visual-based food grading for both humans and machines. Taking lettuce samples as an example, an image dataset that considered the environmental illumination variations was first established. This dataset encompasses human visual grading scores obtained from sensory panels as well. In contrast to current studies that utilize a single grader or L*a*b* color features to assess sample freshness, our study reveals a substantial impact of environmental illumination on both human perception (p<0.0001) and L*a*b* color features (p<0.0001). In order to enhance the performance of machine vision-based freshness prediction, multitask learning protocols were incorporated into the proposed new network architectures. This allowed the simultaneous prediction of both sample freshness and illumination conditions. In comparison to commonly used generic convolutional neural network models and vision transformer models, the newly proposed model exhibited superior freshness prediction performance. It minimized the prediction error by 20.36%, outperforming the generic ResNet model. This research represents the first quantitative study addressing human and machine perceptions under varied illumination conditions for food quality evaluation. The findings are anticipated to play a pivotal role in expediting the integration of machine vision applications into food engineering practices.

Abstract PS05-06: Outcomes of Surveillance using Contrast Enhanced Mammography in Women with a Personal History of Breast Cancer

Abstract Background Women with a personal history of breast cancer (PHBC) have a high rate of subsequent breast malignancy. Annual mammography with selective ultrasound has been the standard method of surveillance after breast cancer for many years, aiming for early detection, treatment and improved survival. In surveillance populations, interval cancers, which can account for ~30% of subsequent breast cancers, are more likely to be larger, hormone receptor negative and lymph node positive than cancers detected by surveillance (Lee et al, Radiology 2021). Interval cancer rates of 3.6 per 1000 mammographic screens have been reported previously in women with PHBC (Houssami et al, JAMA 2011). For women with PHBC a more sensitive surveillance approach may be justified, noting mammography has lower program sensitivity in PHBC surveillance than in screening. Magnetic resonance imaging (MRI) is used selectively but with resource and access limitations. Contrast enhanced mammography (CEM) offers a more sensitive modality than conventional mammography with specificity comparable to MRI, but its utility for surveillance is uncertain. Methods Retrospective study of 1,190 women with PHBC who commenced annual CEM surveillance in an Australian hospital setting between June 2016 and December 2022 (Elder et al, Breast Cancer Res Treat 2023) combining outcomes of initial CEM and any subsequent surveillance imaging over that period, including incident surveillance-detected cancers and interval cancers (cancers diagnosed in the year following a negative surveillance episode), recalls for assessment, the contribution of contrast to recall, and pathology and treatment details for cancer diagnoses. Outcomes were reported using descriptive statistics and hazards modelling. Results There were 3,784 episodes for analysis: 1,190 first CEM surveillance episodes, and 2,594 subsequent surveillance episodes of which &amp;gt;90% were contrast based imaging. 79% of women had at least three annual rounds of surveillance imaging. 186 cases from the total 3784 surveillance episodes were recalled for assessment (recall rate 4.9%). 72 (39%) recalled cases identified malignant lesions (true positives (TP)), with 50 invasive cancers and 22 cases of DCIS. 114 (61%) recalled cases were false positives (FP). 51% of cases were only recalled due to contrast and 35% of these were TP. Invasive cancers were predominantly stage 1 (64%) or stage 2 (32%) and most were grade 2 (44%) or grade 3 (47%). The median invasive cancer size was 16mm (IQR 9-25mm). 62% of invasive cancers were hormone receptor positive HER2 negative, and 24% were triple negative. The median DCIS size was 19mm (IQR 10-26mm) with only a single low grade case. 40% of invasive cancers and 59% of DCIS were recalled due to contrast. Comparison of tumour features indicates similarities between contrast-directed recalls and other diagnoses; conclusive findings would require a larger sample. Five interval cancers were identified, of which three were asymptomatic and detected on surveillance imaging scheduled early for other reasons. Thus, the rate of symptomatic interval cancers was 0.8 per 1000 screens (program sensitivity 96.0%). Surveillance-detected cancer rates differed significantly by index cancer subtype (χ2=11.9, p=0.0026), with highest rates for women with triple negative index cancers. Incidence cancer rates were higher among the 6.9% of women with moderate or marked BPE at first CEM surveillance episode (χ2=8.8, p=0.032), but did not differ significantly by age group (χ2=5.2, p=0.39) nor breast density (χ2=4.7, p=0.19). Conclusions Routine use of CEM in annual surveillance of women with PHBC led to 1.85-fold increase in the detection of clinically significant malignant lesions, with lower interval cancer rates than previous published series of women with PHBC. CEM appears to increase the sensitivity of surveillance programs for women with PHBC, improving on imaging without contrast. Citation Format: Julia Matheson, Carolyn Nickson, Kenneth Elder, Allan Park, Allison Rose, Bruce Mann. Outcomes of Surveillance using Contrast Enhanced Mammography in Women with a Personal History of Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-06.

Analytical computation of stress intensity factor for multi-physics problems

This work presents a methodology for the analytical calculation of the stress intensity factor when the stress distribution on the crack surfaces is non-homogeneous. At first, a polynomial function is used to express the non-homogenous stress distribution. Subsequently, the principle of superposition of effects is applied, and the stress intensity factor is computed by multiplying each polynomial term by its respective geometric factor. Finite element fracture model is used to compute the geometric factor of the single polynomial grade. To explain the method, a spherical body is considered, with central and superficial cracks. Each geometric factor depends on a normalized geometrical parameter (the ratio between the crack length and sphere radius). The proposed methodology is applied to determine the stress intensity factor in the case of a crack driving force caused by diffusive fields, such as the concentration gradient in particles of electrodes active material in lithium-ion batteries. The methodology allows to speed up the fracture computation, then it is used to give electrode design guidelines to limit the fracture likeliness and mechanical degradation in lithium-ion batteries, as well as it is the basis for the development of algorithms assessing the capacity loss and the remaining useful life of lithium-ion batteries in real-time.

Classification of postoperative complications in plastic and reconstructive surgery: a systematic review

"Introduction: Postoperative complications are an integral aspect of the surgical audit, being a surrogate marker of surgical quality. Despite demonstrated efficacy in most specialties, there is scarce validation of current systems in plastic and reconstructive surgery, let alone a system unique to the specialty. This review aims to establish the efficacy of current systems in plastic and reconstructive surgery and formulate a classification unique to our specialty. Methods: A PUBMED literature search was performed in January 2023 encompassing all available literature. Search terms included ‘classification’, ‘grading’, ‘postoperative complications’ and ‘adverse events’. Further additions through bibliographic linkage generated a total of 363 articles. Results: Twenty-four papers were related to PRS. Sixteen used current systems to describe postoperative complications, whereas eight papers used a system designed uniquely for PRS. The downfall of conventional systems is the simplicity of return to the operating theatre, constituting a single grade in the Clavien-Dindo Classification. Return to theatre has a broad scope for heterogeneity in plastic and reconstructive surgery, particularly in reconstructive patients. A modification of the Clavien-Dindo Classification is proposed. Conclusion: There is limited efficacy of current classification systems for postoperative complications in plastic and reconstructive surgery nor a well-validated system unique to the specialty. A modified system with a detailed emphasis on return to the theatre will be of value to plastic and reconstructive surgery and ideally correlate with important outcomes. This will be validated in a retrospective review of the complication audit from the developing institution."

The effects of an IV fluid bolus on mitral annular velocity and the assessment of diastolic function: a prospective non-randomized study

BackgroundAbnormal diastolic function is an independent predictor of adverse postoperative outcomes. Mitral annular tissue Doppler velocity (e’) is a key parameter for assessing diastolic function. The purpose of this study was to confirm that an acute increase in preload did not significantly impact the intraoperative measurement of e’ and secondarily evaluate the impact of this acute intravascular volume increase on the clinical assessment of diastolic function using a previously described simplified algorithm.MethodsThis was a prospective, non-randomized study in adult patients undergoing elective cardiac surgeries requiring transesophageal echocardiographic monitoring, arterial pressure and Swan-Ganz catheter placements as part of the surgical procedure. Following baseline echocardiographic and hemodynamic measurements, 500 ml of crystalloid solution was infused over 10 min. Hemodynamic and echocardiographic measurements were repeated 5 min after fluid administration.ResultsComplete data sets were available from 84 of the 100 patients who were enrolled in this study. There was no significant change in the values of e’. The average baseline was 7.8 ± 2.0 cm/s (95%CI: 7.4, 8.2) and 8.1 ± 2.4 (95%CI: 7.6, 8.6) following the fluid bolus (p = 0.10). All hemodynamic variables associated with increased intravascular volume (central venous pressure, pulmonary arterial pressures and stroke volume variation) changed significantly. The overall distribution of diastolic function grades did not change following fluid administration (p = 0.69). However, there were many individual patient differences. When using this simplified algorithm, functional grading changed in 35 patients. Thirty of these 35 changes were only a single grade shift. 22 patients had worse functional grading after fluid administration while 13 had improved grading. Nine patients with normal diastolic function at baseline demonstrated diastolic dysfunction after fluid administration while 6 patients with baseline dysfunction normalized following the fluid bolus.ConclusionWe confirmed that e’ is a robust measurement that is reproducible in the intraoperative setting despite variable vascular volume loading conditions, however, the clinical assessment of diastolic function was still altered in 42% of the patients following an intravenous fluid bolus.

Solubility evaluation of palm-based Mono-diacylglycerols (MDAGs) in food grade solvent (hexane, ethanol, acetone, water) using QSPR model approach

Mono-diacylglycerols (MDAGs) are emulsifiers widely used in the food industry. MDAGs based on refined bleached deodorized palm stearin (RBDPS) have not been widely developed. MDAGs have been synthesized using glicerolysis between RBDPS and glycerols. Due to their low solubility in food-grade solvents (hexane, ethanol, acetone, and water), it has been difficult to purify or fractionate MDAGs only by a simple method. This research attempted to develop a model of MDAGs solubility in food-grade solvents and understand the parameters that influence the solubility of MDAGs in food-grade solvents. The process used a combination of experimental data collection and quantitative structure–property relationship (QSPR) models. The QSPR model for MDAGs solubility in a single and binary solvent demonstrated that the descriptors of Δ dipole moment (Δµ), E HOMO, E LUMO, electronic energy, gap energy HOMO-LUMO (ΔE1, ΔE2) softness (S), electrophilicity index (ω), and electron transfer (ΔN) have a significant impact in determining the solubility of MDAGs. Both the single and the binary solvents solubility models can give satisfactory prediction results: the square of the correlation coefficient (R2pred) was 0.933 and 0.948, and the root-mean-square error (RMSE) was 0.075 and 0.031, respectively, for the whole data set. In addition, this paper provided a new and effective method for predicting the solubility of MDAGs in single and binary food-grade solvent systems.

A comparison of visual and direct assessments of lumbar spine posture

BackgroundPosture is assessed clinically and used to guide treatment of low back pain. Collectively, the relevance of posture and clinical postural assessments have come under scrutiny. This study aimed to determine (a) the intra-rater and inter-rater reliability of visual assessments of lumbar lordosis, and (b) the agreement between visual and direct postural assessments. MethodsTen physiotherapists visually assessed the lumbar lordosis from 3D scans of 50 asymptomatic participants, and 15 duplicates, using a grading scale of deviations (range: 0 = normal to 3 = severe). Lumbar lordosis angle was directly assessed using the Vitus Smart 3D whole body scanner. Cohen's Kappa was used to determine the intra-rater and inter-rater reliability of visual assessments, with polyserial correlation (ps) used to determine the agreement between visual and direct assessments. ResultsOverall, 93% and 83% of all intra-rater and inter-rater differences in visual assessments were within a single grade point, respectively. The intra-rater and inter-rater reliability of visual assessments was moderate (κ (95%CI): 0.56 (0.45, 0.67)) and slight (κ (95%CI): 0.13 (0.08, 0.19)), respectively. The agreement between visual and direct assessments was moderate (ps = −0.41, p = 0.04). ConclusionVisual assessments of lumbar posture demonstrated moderate repeatability and agreement with quantitative assessments. While agreement between assessors was slight, 83% of the visual ratings were within a single grade point, suggesting greater coherence among clinicians than our statistics suggested. As with any clinical assessments involving uncertainty, postural assessment should not solely guide treatment.

Late Toxicity of Prostate Ultrahypofractionated Radiation Therapy Compared With Moderate Hypofractionation in a Randomized Trial

PurposeWe report late toxicity, quality of life (QOL) and urinary symptom score with prostate cancer radiotherapy in a randomized trial comparing moderate hypofractionation (MHF) and ultrahypofrationation (UHF) Methods and MaterialsPatients with intermediate and high risk prostate cancer were randomized to either Arm 1 (70Gy/28 fractions) or Arm 2 (36.25Gy/5 weekly fractions). Late toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) and Radiation Therapy Oncology Group/Subjective, Objective, Management, Analytic (RTOG/SOMA) scales. QOL was assessed with the Expanded Prostate Inventory Composite-26 Short Form (EPIC-26) and urinary function with the International Prostate Symptom Score (IPSS). ResultsEighty participants were randomized. Two from Arm 1 withdrew, leaving 36 patients in Arm 1 and 42 in Arm 2. There were no significant differences in baseline characteristics, except for worse IPSS in Arm 2. No difference was observed in freedom from grade 3 or worse toxicity between treatments (p=0.921), with only a single grade 3 event in each arm. There was no significant difference in freedom from grade 2 or worse toxicity (p=0.280). No difference was observed in freedom from grade 2 or worse genitorurinary toxicity, with cumulative probabilities of 69.0% and 87.0% at 5-years for Arms 1 and 2, respectively (0.132). No difference was observed in freedom from grade 2 or worse gastrointestinal toxicity, with cumulative probabilities of 74.0% in Arm 1 and 80.0% in Arm 2 (p=0.430). There were no significant differences in EPIC-26 QOL between arms. ConclusionUHF, delivered weekly, is well tolerated with no significant differences in freedom from late toxicity compared to MHF.

CAN ACUPUNCTURE BE A PART OF THE TREATMENT FOR BREAST CANCER-RELATED LYMPHEDEMA? A SYSTEMATIC REVIEW OF THE SAFETY AND PROPOSED MODEL FOR CARE

Acupuncture is a potential therapy for breast cancer-related lymphedema (BCRL). Despite a recent meta-analysis on efficacy, data on acupuncture safety in BCRL are lacking. Current clinical guidelines recommend avoiding needling in the upper extremity affected by lymph node dissection. We undertook a systematic review focusing on acupuncture safety and treatment protocols in clinical trials for BCRL. Literature searches were conducted in PubMed, Ovid, CINAHL, and Cochrane library. Eight clinical trials on acupuncture for BCRL were analyzed. The Standards of Acupuncture intervention (STRICTA 2010) and Cochrane risk of bias (RoB2 2019) were applied to assess methods for acupuncture interventions within Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Quantity and severity of adverse events (AE) were reviewed. A total of 189 subjects participated in 8 clinical trials with 2965 acupuncture treatments. No serious adverse events (SAE) were reported regardless of treatment laterality or protocol, with only a single grade 2 skin infection in 2,965 total treatments (.034%), including 1,165 bilateral and 225 ipsilateral treatments. Our comprehensive review of clinical trials of acupuncture for BCRL demonstrated no significant adverse events in 2,965 treatments, including 1,390 in the affected limb. An approach for routine integration of acupuncture into BCRL maintenance therapy is proposed.

A First-in-Human, Phase 1, Dose Escalation Study of Sgr-2921 As Monotherapy in Subjects with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Background Cell division cycle 7-related protein kinase (CDC7), or DBF4-dependent CDC7 kinase (DDK), is a cell cycle kinase that maintains DNA replication by phosphorylation and activation of the minichromosome maintenance protein 2 and 4 (MCMs), components of the replicative DNA helicase. Due to the central role of CDC7 in maintenance of the replication fork integrity, chemical inhibition of CDC7 kinase can ultimately lead to cancer cell death. SGR-2921 is an oral, small molecule inhibitor of CDC7. Preclinical studies demonstrate that, among all cell lines tested, SGR-2921 has the most potent anti-proliferative activity in AML. Potent antitumor activity has also been demonstrated in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) AML models. This antitumor response is observed in animal models representative of difficult to treat patient populations and appears to be agnostic of serious mutations (including those with p53 mutations and FLT3 mutations), BTK resistance, and multiple prior lines of treatment. Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or high-risk (HR) or very high-risk (VHR) myelodysplastic syndrome (MDS) have low response rates and poor overall survival. Considering the potent preclinical activity of SGR-2921 in AML and MDS models, coupled with the high unmet medical need in this population, SGR-2921 is being evaluated in patients with R/R AML and HR/VHR MDS. Study Design and Methods This is a phase 1, FIH, open-label, single-agent, two-arm, dose escalation study (NCT#05961839) designed to evaluate safety and tolerability and identify the recommended phase 2 dose (RP2D) of SGR-2921 as monotherapy in subjects with R/R AML, HR MDS, or VHR MDS. The study utilizes a hybrid accelerated titration design with single patient cohorts that transitions to a 3+3 design once a single Grade 2 event or DLT is observed. This is a multicenter global study (US, Spain and France) with an estimated study recruitment start date in October, 2023. SGR-2921 will be administered orally, once daily, utilizing a 5-day on and 9-day off dosing schedule over a 28-day cycle. Up to a maximum of 144 patients will be enrolled in the dose escalation and exploratory cohort phase of the study. To evaluate the effect of CYP3A4 inhibition on SGR-2921 exposure, subjects will be enrolled into one of two staggered, parallel study treatment arms, according to concomitant administration with (Arm B) or without (Arm A) azole antifungals that are strong CYP3A4 inhibitors at time of first dose. Safety and tolerability must be demonstrated in treatment Arm A, at the first two dose levels before initiating treatment Arm B. A single dose PK run-in will be required for subjects enrolled into the first 3 cohorts of each treatment arm. Subjects will be treated at increasing doses of study drug until all dose levels have been investigated or any dose level is found to exceed the maximum tolerated dose (MTD). A RP2D will be selected from one of the tolerable dose levels which will not exceed the MTD (see Figure 1 for study design). Key study inclusion criteria include: Age ≥ 18 years of age; Life expectancy ≥ 8 weeks; Confirmed diagnosis of R/R AML or HR and VHR MDS; Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Key study exclusion criteria include: Active malignancies not related to AML or MDS within two years prior to the first dose or requiring ongoing treatment; Clinical evidence of central nervous system (CNS) or pulmonary leukostasis; ≥ Grade 3 disseminated intravascular coagulation, or active CNS leukemia; QT interval corrected for heart rate per Fridericia's formula ≥470 msec during screening ECG. The study primary objectives are to evaluate the safety and tolerability of SGR-2921 as monotherapy and identify RP2D including MTD. Secondary objectives include evaluating the pharmacokinetics (PK) of SGR-2921 and investigating preliminary antitumor activity (composite complete remission rate, objective response rate, duration of response, etc.).

Comparison of screw placement guided by O-arm navigation and ultrasound volume navigation in minimally invasive transforaminal lumbar interbody fusion

To compare the effectiveness of O-arm navigation and ultrasound volume navigation (UVN) in guiding screw placement during minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) surgery. Sixty patients who underwent MIS-TLIF surgery for lumbar disc herniation between June 2022 and June 2023 and met the selection criteria were included in the study. They were randomly assigned to group A (screw placement guided by UVN during MIS-TLIF) or group B (screw placement guided by O-arm navigation during MIS-TLIF), with 30 cases in each group. There was no significant difference in baseline data, including gender, age, body mass index, and surgical segment, between the two groups ( P>0.05). Intraoperative data, including average single screw placement time, total radiation dose, and average single screw effective radiation dose, were recorded and calculated. Postoperatively, X-ray film and CT scans were performed at 10 days to evaluate screw placement accuracy and assess facet joint violation. Pearson correlation and Spearman correlation analyses were used to observe the relationship between the studied parameters (average single screw placement time and screw placement accuracy grading) and BMI. The average single screw placement time in group B was significantly shorter than that in group A, and the total radiation dose of single segment and multi-segment and the average single screw effective radiation dose in group B were significantly higher than those in group A ( P<0.05). There was no significant difference in the total radiation dose between single segment and multiple segments in group B ( P>0.05), while the total radiation dose of multiple segments was significantly higher than that of single segment in group A ( P<0.05). No significant difference was found in the accuracy of screw implantation between the two groups ( P>0.05). In both groups, the grade 1 and grade 2 screws broke through the outer wall of the pedicle, and no screw broke through the inner wall of the pedicle. There was no significant difference in the rate of facet joint violation between the two groups ( P>0.05). In group A, both the average single screw placement time and screw placement accuracy grading were positively correlated with BMI ( r=0.677, P<0.001; r=0.222, P=0.012), while in group B, neither of them was correlated with BMI ( r=0.224, P=0.233; r=0.034, P=0.697). UVN-guided screw placement in MIS-TLIF surgery demonstrates comparable efficiency, visualization, and accuracy to O-arm navigation, while significantly reducing radiation exposure. However, it may be influenced by factors such as obesity, which poses certain limitations.

Vactosertib, a Novel TGFb Type I Receptor Kinase Inhibitor, Improves T-Cell Fitness:a Single-Arm, Phase 1b Trial in Relapsed/Refractory Multiple Myeloma

The prognosis for Multiple Myeloma (MM) patients (pts) has improved substantially over the past two decades with the success of immunomodulatory drugs (IMiDs), monoclonal antibodies, chimeric antigen receptor (CAR) T-cells and bispecific T-cell engagers (BiTEs) that broke the circulus vitiosus of tumor-induced immunosuppression to reengage the immune system. Functional blockade of the transforming growth factor-beta (TGF) signaling pathway improves the efficacy of cytotoxic and immune therapies, therefore we investigator the impact of TGF-inhibition in an steroid free regimn. Methods: We conducted a phase 1b study to determine the safety, efficacy, and maximal tolerated dose (200 mg po bid) of the potent, orally-available TGF type I receptor kinase inhibitor vactosertib in relapsed and/or refractory multiple myeloma (RRMM) pts who had received -2 lines of chemoimmunotherapy in combination with standard dosage of Pomalidomide without any corticosteroids. Results: Twenty one pts were enrolled in the phase 1b dose escalation cohort and received vactosertib plus pomalidomide as indicated (Fig. 1A). Pts' characteristics are described in Table 1The summary of grade 1-4 adverse events is shown (Table 2). A single grade 4 elevated bilirubin (5%) and a single grade 4 elevated lipase (5%) were observed as well as four grade 4 events of decreased neutrophils (19%). Four pts demonstrated a PR, two had a MR, nine had SD and four had disease progression (Fig. 1B). The median time to response for all pts and the responders eight weeks and median duration of response was ~12 weeks. The best overall response for individual pts to treatment is shown (Fig. 1C). Clinical activity was observed across all four dose levels (Table 3). To probe the tumor intrinsic anti-myeloma activity of vactosertib, we first determined the relative effect of vactosertib compared to the IMiDs pomalidomide and lenalidomide (Fig. 2A, B). The effect of vactosertib was greater than that observed with either lenalidomide or pomalidomide. MMCLs and patient CD138 + cells were then treated with vactosertib in combination with pomalidomide, and importantly, vactosertib with pomalidomide synergistically reduced myeloma viability (Fig. 3A). We next probed the systemic, tumor extrinsic effects of vactosertib by analyzing cytokines immune and tumor cells present within patient BM samples. (Fig. 4A). (Fig. 4B). Therefore, we explored the immunophenotype of CD8 + T-cells isolated from patient BM prior to and at the EOT. The relative percentage of T-cells that expressed the immunosuppressive markers programmed cell death-1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), B and T lymphocyte attenuator (BTLA), and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) was reduced following treatment relative to their expression prior to treatment (Fig. 4C). Results indicated that vactosertib and pomalidomide treatment in vivo reduced PD-1, TIM3, BTLA and CTLA-4 expression on patient CD8 + T-cells. Next, CD8 + T-cells were isolated from patient peripheral blood and cultured in the presence of TGF-1, vactosertib, pomalidomide, or vactosertib plus pomalidomide (Fig. 5B). Treatment of patient CD8 + T-cells with vactosertib decreased PD-1 expression up to 40% and decreased TIM3 expression up to 65%. Pomalidomide alone did not significantly reduce PD-1, TIM3, BTLA, or LAG-3 on patient CD8 + T-cells. Vactosertib and pomalidomide also reduced TIM3 levels on CD8 + T-cells from most pts. (Fig. 5C, D). (Fig. 5 G, H). Results indicated that vactosertib or pomalidomide did not increase CD138 + cell death (Fig. 5I). Conclusion: Vactosertib combined with pomalidomide was well-tolerated at all doses, had a manageable adverse event profile and induced durable responses with 80% progression-free survival (PFS-6) at 6 months, Vactosertib reduced TGF- in patient bone marrow and suppressed PD-1 expression on CD8 + T-cells and lead to reduction of PD-L1/PD-L2 expression on CD138 + cells and enhanced autologous T-cell cytotoxicity. Taken together, our results support the safety and efficacy of vactosertib to treat RRMM and revealed that vactosertib modulates the T-cell immunophenotype and reinvigorates T-cell fitness.

Efficacy and Safety of Fedratinib in Patients with Myelofibrosis Previously Treated with Ruxolitinib: Results from the Phase 3 Randomized FREEDOM2 Study

Introduction Patients (pts) with myelofibrosis (MF) treated with the Janus kinase inhibitor (JAKi) ruxolitinib (RUX) show spleen volume reduction (SVR) and symptom reduction. However, most develop RUX intolerance or relapsed/refractory (R/R) disease and survival rates after RUX discontinuation are poor. Fedratinib (FEDR) delivered SVR and symptom reduction in the JAKARTA2 and FREEDOM studies (C Harrison et al. Am J Hematol 2020; V Gupta et al. Blood 2022). FREEDOM2 (NCT03952039) was a phase 3, open-label, randomized study to evaluate the safety and efficacy of FEDR compared with best available therapy (BAT) in pts with MF previously treated with RUX. Methods Pts aged ≥ 18 years with primary, post-polycythemia vera, or post-essential thrombocythemia MF with Dynamic International Prognostic Scoring System (DIPSS) score ≥ intermediate-2, splenomegaly (≥ 450 cm 3), platelets ≥ 50 x 10 9/L, peripheral blood myeloblasts &amp;lt; 5%, and normal baseline thiamine, R/R or intolerant to RUX, were randomized 2:1 to FEDR 400 mg/day or BAT in 28-day cycles, with stratification by spleen size, platelet count, and RUX R/R vs intolerant. Crossover to FEDR was permitted for progressive disease or after cycle 6 (EOC6) response assessment. Pts were treated until intolerance or lack of efficacy and followed-up every 3 months until death, withdrawal of consent, or study closure. The primary endpoint was SVR ≥ 35% (SVR35) at EOC6; secondary endpoints included symptom response (≥ 50% reduction in total symptom score measured by Myelofibrosis Symptom Assessment Form), SVR ≥ 25% (SVR25), durability of SVR and symptom response, and safety. Results Overall, 201 pts were initially randomized and treated, 134 and 67 pts in the FEDR and BAT arms, respectively; subsequently, 46 (68.7%) pts from the BAT arm crossed over to FEDR. Median (interquartile range) age was 70 (64-74) years, 52.2% were male, and most had primary MF (54.7%) and intermediate-2 DIPSS risk (76.1%). Assessed by aggregated group, most pts in the BAT arm received RUX (70.1%), hydroxyurea (10.4%), or RUX plus hydroxyurea (7.5%). At the data cutoff of December 27, 2022 (median follow-up, 15 months), pts receiving FEDR had significantly higher rates of SVR35 at EOC6 compared with BAT (35.8% vs 6.0%; P &amp;lt; 0.0001), as well as superior SVR25 at EOC6 and SVR35 during the full treatment course ( Table, Figure). SVR35 benefit with FEDR was observed across subgroups. The FEDR arm also showed higher rates of symptom response at EOC6 compared with BAT (34.1% vs 16.9%; P = 0.0033; Table). Median treatment duration was 43 weeks of FEDR and 24.7 weeks of BAT. During the first 6 cycles in the safety population: 70 (52.2%) pts on FEDR and 20 (29.9%) pts on BAT had dose interruption/reduction; median time to first reduction/interruption was 44.0 days for FEDR and 56.5 days for BAT. Treatment-emergent adverse events (TEAEs) leading to permanent treatment discontinuation occurred in 13 (9.7%) and 4 (6.0%) pts in the FEDR and BAT arms, respectively, during the first 6 cycles. During the first 6 cycles, 132 (98.5%) pts on FEDR and 65 (97.0%) pts on BAT had ≥ 1 TEAE; treatment-related AEs (TRAEs) occurred in 109 (81.3%) and 23 (34.3%) pts in the FEDR and BAT arms, respectively. The most frequently occurring TRAEs with FEDR were diarrhea (38.1% FEDR vs 0.0% BAT) and nausea (32.1% FEDR vs 1.5% BAT); most cases were grade 1/2. Grade 3/4 TRAEs occurred in 52 (38.8%) pts in FEDR and 8 (11.9%) pts in BAT arms, most frequently thrombocytopenia (11.9% FEDR vs 3.0% BAT) and anemia (9.0% FEDR vs 9.0% BAT). In the FEDR arm, 22 (16.4%) pts had thiamine levels below normal range, compared with 2 (3.0%) pts receiving BAT; most cases occurred prior to the study amendment of prophylactic thiamine supplementation. There was a single grade 1 case of suspected Wernicke's encephalopathy in the FEDR arm during cycle 3, which resolved fully 24 hours after thiamine supplementation (0 cases in BAT arm). Two pts each in FEDR and BAT arms had TRAEs of infection. Conclusions In this phase 3 randomized study in pts with MF and prior RUX treatment, FEDR demonstrated superior SVR and symptom response rates compared with BAT. Most pts on BAT received RUX, highlighting a clinical need for an alternative JAKi. Differences in AE and discontinuation rates in the first 6 cycles are consistent with other studies comparing JAKi with BAT. AE mitigation strategies were effective and no new safety concerns for FEDR were identified. Study support Bristol Myers Squibb