Volume Reduction Research Articles

A reduction in tumor volume exceeding 65% predicts a good histological response to neoadjuvant chemotherapy in patients with Ewing sarcoma.

No consensus exists for tumor volume response criteria in patients with Ewing sarcoma. This study aimed to identify an optimal cutoff for predicting a good histological response by analyzing tumor volume changes and tumor necrosis after neoadjuvant chemotherapy. We performed a retrospective analysis of 184 Ewing sarcoma patients, analyzing tumor volume changes before and after neoadjuvant chemotherapy. Patients were divided into two groups based on histological response: good (tumor necrosis ≥ 95%) and poor (tumor necrosis < 95%) responders. The receiver operating characteristic (ROC) area under the curve (AUC) method was used to determine the optimal thresholds for predicting the histological response. Additionally, the prognostic value of this cutoff for relapse-free survival was assessed. Out of 184 patients, 83 (45%) had tumor necrosis ≥ 95%, while 101 (55%) had tumor necrosis < 95%. ROC analysis identified the optimal cutoff for a good histological response as over 65% tumor volume reduction (AUC = 0.69; p < 0.001). Patients with volume reduction of ≥ 65% had a higher likelihood of a good histological response than those with lesser reductions (p = 0.004; odds ratio = 2.61). Multivariable analysis indicated a correlation between poor histological response and reduced relapse-free survival (hazard ratio = 2.17; p = 0.01), while tumor volume reduction itself did not impact survival. We reported that a tumor volume reduction of ≥ 65% was able to predict a good histological response in Ewing sarcoma patients. We recommend preoperative tumor volume assessment to identify patients at greater risk for poor histological response who could benefit from more intensive chemotherapy protocols or additional radiotherapy.

Evaluation of augmented infiltration based LIDs for low lying urbanizing coastal catchments: a case study of Chennai city, India

ABSTRACT The study assessed the effectiveness of infiltration-based Low Impact Development (LID) techniques and augmented infiltration LIDs (such as recharge shaft) in a coastal urban catchment in India using a semi-coupled approach between numerical models VS2DI and Storm Water Management Model (SWMM). Site specific VS2DI modelling indicated that the infiltration LIDs resulted in more saturation excess runoff due to the soil’s insufficient hydraulic conductivity and increased lateral flow. Catchment-scale modeling indicated that LIDs significantly improved water retention (p ≪ 0.05), with a 35% reduction in total runoff volume. The recharge shafts were shown to be more efficient in reducing runoff volume and peak runoff, particularly for high runoff rates (more than 22 mm/hr). The study suggests that direct recharge to the aquifer through recharge shafts could be a suitable solution to manage runoff and meet the demand for domestic water supply during times of water scarcity in coastal urban catchments.

Efficiency of labyrinth vs ogee spillways at high hydraulic heads - case study in Zambia

A new over-the-dam spillway and 3m dam raising was selected as the preferred option for resolving matters in the interest of safety for an existing dam in Zambia. The cost of supplying concrete at the dam site has the greatest effect on overall project capital costs, and thus optimising the size of the concrete spillway is critical. Both ogee and labyrinth weir designs were developed for a hydraulic head of 5m in the safety check flood. The ogee shape design was developed to achieve high efficiency and required a weir width of 81m. For labyrinth weirs, a limiting factor to the allowable head is the ratio between the water head and weir height above its foundation apron. Using published state-of-the-art research, sixty labyrinth weir configurations were tested, with varying angles, leg lengths, and number of cycles. The optimal of these configurations was chosen as the one with the minimum overall spillway width and volume of concrete. This labyrinth configuration provided a spillway width of 64.45m, and a 22% potential reduction in concrete volume compared to the ogee. The labyrinth design was taken forward for CFD modelling to prove the concept and for further development into a detailed design.

Laser interstitial thermal therapy (LITT) for pediatric low-grade glioma-case presentations and lessons learned.

The surgical treatment of brain tumors has developed over time, offering customized strategies for patients and their specific lesions. One of the most recent advances in pediatric neuro-oncological surgery is laser interstitial thermal therapy (LITT). However, its effectiveness and indications are still being evaluated. The aim of this work is to review the current literature on LITT for pediatric low-grade gliomas (pLGG) and evaluate our initial results in this context. We retrospectively reviewed our pediatric neurosurgery database for patients who received LITT treatment between November 2019 and December 2023. We collected data on the indications for LITT, technical issues during the procedure, and clinical and radiological follow-up. Three patients underwent 5 LITT procedures for pLGG. The lesion was thalamo-peduncular in one patient, cingulate in one, and deep parietal in one patient. Two patients had a previous open resection done and were diagnosed with pLGG. One patient underwent a stereotaxic biopsy during the LITT procedure that was non-diagnostic. The same patient underwent a later open resection of the tumor in the cingulate gyrus. There were no surgical complications and all patients were discharged home on the first post-operative day. The follow-up period was between 20 and 40 months. Radiological follow-up showed a progressive reduction of the tumor in patients with LGG. Laser interstitial thermal therapy is a minimally invasive treatment that shows promise in treating deep-seated pLGG in children. The treatment has demonstrated a reduction in tumor volume, and the positive results continue over time. LITT can be used as an alternative treatment for tumors located in areas that are difficult to access surgically or in cases where other standard treatment options have failed.

Effect of NFX-179 MEK inhibitor on cutaneous neurofibromas in persons with neurofibromatosis type 1.

This phase 2a trial investigated the efficacy of NFX-179 Topical Gel, a metabolically labile MEK inhibitor, in the treatment of cutaneous neurofibromas (cNFs) in neurofibromatosis type 1. Forty-eight participants were randomized to four treatment arms: NFX-179 Topical Gel 0.05%, 0.15%, and 0.5% or vehicle applied once daily to five target cNFs for 28 days. Treatment with NFX-179 Topical Gel resulted in a dose-dependent reduction in p-ERK levels in cNFs at day 28, with a 47% decrease in the 0.5% NFX-179 group compared to the vehicle (P = 0.0001). No local or systemic toxicities were observed during the treatment period, and systemic concentrations of NFX-179 remained below 1 ng/ml. In addition, 20% of cNFs treated with 0.5% NFX-179 Topical Gel showed a ≥50% reduction in volume compared to 6% in the vehicle group by ruler measurement with calculated volume (P = 0.021). Thus, NFX-179 Topical Gel demonstrated significant inhibition of MEK in cNF with excellent safety and potential therapeutic benefit.

Assessing the relative effectiveness of various ultrasound-guided ablation techniques for treating benign thyroid nodules: A systematic review and network meta-analysis.

Benign thyroid nodules (BTNs) represent a prevalent clinical challenge globally, with various ultrasound-guided ablation techniques developed for their management. Despite the availability of these methods, a comprehensive evaluation to identify the most effective technique remains absent. This study endeavors to bridge this knowledge gap through a network meta-analysis (NMA), aiming to enhance the understanding of the comparative effectiveness of different ultrasound-guided ablation methods in treating BTNs. We comprehensively searched PubMed, Embase, Cochrane, Web of Science, Ovid, SCOPUS, and ProQuest for studies involving 16 ablation methods, control groups, and head-to-head trials. NMA was utilized to evaluate methods based on the percentage change in nodule volume, symptom score, and cosmetic score. This study is registered in INPLASY (registration number 202260061). Among 35 eligible studies involving 5655 patients, NMA indicated that RFA2 (radiofrequency ablation, 2 sessions) exhibited the best outcomes at 6 months for percentage change in BTN volume (SUCRA value 74.6), closely followed by RFA (SUCRA value 73.7). At 12 months, RFA was identified as the most effective (SUCRA value 81.3). Subgroup analysis showed RFA2 as the most effective for solid nodule volume reduction at 6 months (SUCRA value 75.6), and polidocanol ablation for cystic nodules (SUCRA value 66.5). Various ablation methods are effective in treating BTNs, with RFA showing notable advantages. RFA with 2 sessions is particularly optimal for solid BTNs, while polidocanol ablation stands out for cystic nodules.

Severe hypoglycemia with reduced liver volume as an indicator of end-stage malnutrition in patients with anorexia nervosa: a retrospective observational study

BackgroundHypophosphatemia due to excessive carbohydrate administration is considered the primary pathogenesis of refeeding syndrome. However, its association with liver injury and hypoglycemia, often seen in severe malnutrition before re-nutrition, remains unclear. Autophagy reportedly occurs in the liver of patients with severe malnutrition. This study aimed to clarify the pathophysiology of liver injury and hypoglycemia by focusing on liver volume.MethodsForty-eight patients with anorexia nervosa with a body mass index (BMI) of < 13 kg/m2 were included (median BMI: 10.51 kg/m2 on admission). Liver volume was measured in 36 patients who underwent abdominal computed tomography (CT), and the “estimated liver weight/ideal body weight” was used as the liver volume index. Seventeen blood test items were analyzed during the first 60 days.ResultsLiver volume significantly decreased when abdominal CTs were conducted shortly before or after hypoglycemia compared to when the scans were performed during periods without hypoglycemia. Five patients with severe hypoglycemia on days 13–18 after admission had a very low nutritional intake; of them, four showed a marked decrease in liver volume. Severe hypoglycemia was accompanied by low serum triglycerides and liver dysfunction. Patients experiencing hypoglycemia of blood glucose levels < 55 mg/dL (< 3.05 mmol/L) (32 patients; median lowest BMI: 9.45 kg/m2) exhibited significantly poorer blood findings for most of the 17 items, except serum phosphorus and potassium, than did those not experiencing hypoglycemia (16 patients; median lowest BMI: 11.2 kg/m2). All patients with a poor prognosis belonged to the hypoglycemia group. Empirically, initiating re-nutrition at 500 kcal/day (20–25 kcal/kg/day), increasing to 700–800 kcal/day after a week, and then gradually escalating can reduce serious complications following severe hypoglycemia.ConclusionsLiver volume reduction accompanied by hypoglycemia, low serum triglyceride levels, and liver dysfunction occurs when the body's stored energy sources are depleted and external nutritional intake is inadequate, suggesting that the liver was consumed as a last resort to obtain energy essential for daily survival. This pathophysiology, distinct from refeeding syndrome, indicates the terminal stage of malnutrition and is a risk factor for complications and poor prognosis. In treatment, extremely low nutrient levels should be avoided.

Pulsed electromagnetic fields (PEMF) as a valid tool in orthognathic surgery to reduce post-operative pain and swelling: a prospective study.

PEMF (pulsed electromagnetic fields) founds application in several medical fields to accelerate bone wounds healing and to reduce inflammation. The aim of our study was to evaluate the effectiveness of PEMF in reducing postoperative swelling and pain in patients undergoing orthognathic surgery. A prospective observational monocentric study was conducted on a sample of 30 patients undergone to orthognathic surgery in Maxillofacial Surgery Unit of University of Naples Federico II. The patients who followed these inclusion criteria were enrolled in the study: age ≥ 18 years, Class III malocclusion, Surgical procedure of Le Fort I osteotomy + Bilateral Sagittal Split Osteotomy (BSSO), Written informed consent. Patients were divided into two groups: Group SD) postoperative standard treatment with medical therapy and cryotherapy, Group SD + PEMF) postoperative standard therapy + PEMF. Each patient underwent a 3D facial scan, at one (1d) and four (4d) days after surgery to compare the swelling reduction. The pain score was assessed through VAS score and analgesics administration amount. In SD + PEMF group, the facial volume reduction between 1d and 4d scan was on average 56.2ml (6.23%), while in SD group, it was 23.6ml (2.63%). The difference between the two groups was 3.6% (p = 0.0168). VAS pain values were significantly higher in SD group compared to SD + PEMF group in the second day after surgery (P = 0.021) and in the total 4 days (P = 0.008). Our data suggest that PEMF is valid tool to promote faster postoperative swelling and pain reduction in patients undergoing orthognathic surgery.

Abstract PO1-16-04: Targeting PKMYT1 Kinase as a Therapeutic Strategy for Treatment of Triple Negative Breast Cancer with Low Molecular Weight Cyclin E (LMW-E) Expression

Abstract Purpose: Low molecular weight isoforms of cyclin E (LMW-E) have been implicated in various human cancers, including triple negative breast cancer (TNBC), and are associated with a poor prognosis. However, targeted therapies for TNBC based on biomarkers are currently lacking. This study aims to investigate LMW-E as a potential therapeutic target in TNBC and evaluate the efficacy of RP-6306, a selective inhibitor of the Protein Kinase, Membrane Associated Tyrosine/Threonine 1 (PKMYT1), in LMW-E-positive breast tumors. Experimental Design: Immunohistochemical (IHC) analysis was performed on pre-treatment tumor specimens from TNBC patients (n=36) to assess the correlation between LMW-E expression, CDK1 phosphorylation at Threonine 14 (pT14), and pathologic complete response to neoadjuvant chemotherapy. LMW-E inducible human mammary epithelial cells (hMEC) and breast cancer cell lines were used to investigate the regulatory effect of LMW-E on PKMYT1, the kinase responsible for CDK1 phosphorylation at T14, and the response to RP-6306, a first in-class and selective inhibitor of PKMYT1. Patient-derived xenograft (PDX) models and transgenic mouse mammary tumor virus (MMTV) models of TNBC expressing human LMW-E (hLMW-E) were also utilized to assess LMW-E as a biomarker for predicting response to RP-6306. Results. Analysis of TNBC tumor biopsies revealed a significant positive correlation between LMW-E expression and CDK1 pT14, and both biomarkers were associated with a lack of pathological complete response to neoadjuvant chemotherapy. In vitro results using LMW-E inducible hMECs and breast cancer cell lines demonstrated that LMW-E up-regulates PKMYT1 and CDK1 pT14, acting as a PKMYT1 binding protein and enhancing PKMYT1 protein stability. High LMW-E protein levels predicted a favorable response to RP-6306, resulting in the accumulation of sub-G1 and polyploid cells, decreased tolerance to replication stress, increased DNA damage, chromosomal breakage, and apoptosis. In vivo treatment of TNBC PDX models and hLMW-E transgenic tumors with RP-6306 resulted in a significant reduction in tumor volume only in mice harboring high LMW-E tumors, while low cyclin E models showed no response. Immunohistochemical analysis confirmed increased γ-H2AX and decreased CDK1-pT14 and Ki67 levels, indicating the efficacy of RP-6306 in both PDX and transgenic models. Conclusion: This study highlights the regulatory axis from LMW-E to PKMYT1 and its predictive value for pathological complete response in TNBC patients receiving neoadjuvant chemotherapy. The selective PKMYT1 kinase inhibitor RP-6306 consistently induced DNA damage and inhibited tumor growth in in vitro and in vivo pre-clinical breast tumor models. Co-expression of LMW-E and CDK1-pT14 in TNBC can be used to stratify patients whose tumors are likely to respond to RP-6306, emphasizing its therapeutic significance. Citation Format: Mi Li, Amriti Lulla, Cansu Karakas, Spiridon Tsavaschidis, Yan Wang, Tuyen Nguyun, Tuyen Bui, Gary Marshall, Kelly Hunt, Khandan Keyomarsi. Targeting PKMYT1 Kinase as a Therapeutic Strategy for Treatment of Triple Negative Breast Cancer with Low Molecular Weight Cyclin E (LMW-E) Expression [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 PO1-16-04.

Mechanical Properties of an Ultrahard In Situ Amorphous Steel Matrix Composite

We report compression tests on micropillars manufactured from bulk specimens of partially devitrified SAM2×5 (Fe49.7Cr17.7Mn1.9Mo7.4W1.6B15.2C3.8Si2.4). Yield strength values of ≈6 GPa are obtained. Such a high strength can be attributed to the higher glass transition temperature (883 K) of this material, which impedes the multiplication of shear bands under loading, and to the presence of hard crystalline domains that result from devitrification of the amorphous powders during powder consolidation. The Vickers hardness of the specimens is found to be strongly correlated to the processing temperature and, hence to the volume of crystalline phases present in the specimens. As the processing temperature is increased, there is a reduction in free volume from the structural relaxation process in the amorphous alloy, leading to the eventual nucleation of crystalline phases of BCC Fe, Cr2B, Cr21.30Fe1.7C6, or Fe23B2C4, during the densification process. These results shed light on the relationship between nanocrystalline domains and the mechanical behavior of Fe‐based amorphous/crystalline composites.

Abstract PO4-17-06: Real World Data: A single institute experience with neoadjuvant endocrine therapy for ER+ breast cancer — clinical response rates, clinical predictors of response and long-term outcomes following breast conserving surgery

Abstract Background: Neoadjuvant endocrine therapy (NET) in postmenopausal women (PMW) with large or locally advanced oestrogen receptor (ER)-rich breast cancer allows more women to be treated by breast-conserving surgery (BCS). A comprehensive analysis of the factors affecting clinical response to NET and the long-term safety of this strategy has been studied. Patients: A retrospective cohort was studied of 435 PMW (median age: 77 years; range: 50-98) with ER-positive breast cancer treated with NET (aromatase inhibition) (median duration: 6.8 months; range 3-43 months), between 2001-15. Clinical response was monitored throughout NET treatment with periodic 3D ultrasound measurements of the primary tumour. All patients went on to have surgery, 55% had adjuvant radiotherapy and all had adjuvant ET for at least 5 years. All patients had routine follow-up (median follow-up 12.3 years). To-date, this represents the largest cohort of patients treated with &amp;gt;3 months NET. Results: Clinical response to NET was excellent, with only 3.2% of tumours progressing on-treatment based on RECIST 1.1 criteria. Mean percentage reduction in tumour on NET was 71%. Response rate (partial/complete response) was 59% and response continued until 12 months and then levelled off. Following NET, over 92% of patients were suitable for BCS and 61% achieved clinical TNM down-staging. Multivariate analysis revealed that only ER level (response highest in patients with Allred scores 7 and 8), and percentage change in tumour volume by 6 weeks were significant predictors of overall clinical response to NET. Clinical response to NET was not associated with node status or tumour grade. BCS following NET had a local disease control rate of 89% (95%CI±0.06) at 10 years, but actuarial local recurrence at 10 years was only 7% in those having radiotherapy compared with 30% in the group who did not receive radiotherapy (P&amp;lt; 0.0001). In addition, the overall recurrence rate (P=0.028) was improved by radiotherapy irrespective of nodal status. Radiotherapy did not improve overall breast cancer-specific survival (BCSS). Systemic recurrence and BCSS was higher with greater nodal involvement. Most patients in this study died of other causes (14-year crude all-cause mortality was 71%). Conclusion: NET followed by BCS is an effective strategy in PMW with ER-rich breast cancer. Excellent clinical response rates are seen even in women with node-positive or high-grade disease. Less than 5% showed evidence of progression. Early response to NET predicts for long-term tumour volume reduction and NET can achieve continued tumour shrinkage for up to 1 year. NET followed by BCS appears a safe treatment approach and offers good long-term outcomes when BCS is followed by adjuvant radiotherapy. Citation Format: Arran K Turnbull, Carlos Martinez-Perez, Charlene Kay, Rebecca Swan, Lorna Renshaw, J Michael Dixon. Real World Data: A single institute experience with neoadjuvant endocrine therapy for ER+ breast cancer — clinical response rates, clinical predictors of response and long-term outcomes following breast conserving surgery [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 PO4-17-06.

Abstract PS05-07: Early prediction of response to Neoadjuvant Immunotherapy in Triple Negative Breast Cancer (TNBC) with DCE-MRI

Abstract Purpose: Neoadjuvant immunotherapy (NIT) in combination with neoadjuvant chemotherapy (NCT) was recently approved for treatment of TNBC patients with increased rates of pathologic complete response (pCR) compared to NCT alone. The aim of this study was to evaluate if dynamic contrast-enhanced (DCE)-MRI performed after 2 and/or 4 cycles of NIT + NCT, can predict which patients will achieve pCR, potentially triaging them to continuation of NIT+NCT or, when appropriate, to de-escalation trials. Alternatively, identified chemoresistant tumors who are unlikely to achieve pCR may be directed to other treatment strategies, including novel targeted trials, and avoid the unnecessary toxicity of NIT. Methods and Materials: Preliminary analysis included 64 patients from prospective IRB-approved study (NCT02276443) with stage I-III TNBC who underwent DCE-MRI at baseline (BL), after 2 cycles (C2), and 4 cycles (C4) of NIT combined with standard of care NCT (Paclitaxel +/- carboplatin). Tumor volumes were calculated using 3 axis measurements of the index lesion at the DCE MRI and percent tumor volume reduction (TVR) between BL, C2, and C4 was calculated. pCR was assessed at surgery after completion of neoadjuvant treatment. Correlation between pCR and TVR was evaluated using ROC analysis. Results: 59% (38/64) of TNBC patients achieved pCR after NIT+NCT. DCE-MRI after 2 cycles of NIT+NCT was able to predict pCR with an AUC of 0.71 (95% CI: 0.57-0.84). TVR &amp;gt;90% at C2 predicted pCR with PPV 86%, and TVR &amp;lt; 35% predicted chemoresistance with NPV 100%. Following 4 cycles of treatment DCE-MRI was able to predict pCR with an AUC of 0.81 (95% CI: 0.69-0.92). TVR &amp;gt;95% at C4 was predictive of chemosensitivity with PPV 82%, while TVR &amp;lt; 75% was predictive of chemoresistance with NPV 100%. Conclusions: DCE-MRI volumetric changes early during NIT + NCT were able to predict pCR status of TNBC patients as either excellent responders or nonresponders, triaging them to SOC neoadjuvant therapy with option for de-escalation trials, or targeted therapies, respectively. These preliminary results will be validated in the larger cohort after completion of the ongoing prospective clinical trial. Citation Format: Gaiane Rauch, Mary Guirguis, Miral Patel, Rosalind Candelaria, Rania Mohamed, Tanya Moseley, H. T. Carisa Le-Petross, Jessica Leung, Gary Whitman, Deanna Lane, Marion Scoggins, Frances Perez, Jia Sun, Sanaz Pashapoor, Zhan Xu, Jason White, Peng Wei, Brandy Reed, Jong Bum Son, Ken-Pin Hwang, Bikash Panthi, Anil Korkut, Lei Huo, Kelly Hunt, Alyson Clayborn, Jennifer Litton, Vicente Valero, Debu Tripathy, Clinton Yam, Wei Yang, Jingfei Ma, Beatriz Adrada. Early prediction of response to Neoadjuvant Immunotherapy in Triple Negative Breast Cancer (TNBC) with DCE-MRI [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 PS05-07.

RESISTANCE TRAINING PRESCRIPTION FOR ATHLETES DURING PERIODS OF PLANNED DE-LOADING: A SURVEY OF STRENGTH AND CONDITIONING COACHES

INTRODUCTION &amp; AIMS Implementing resistance training (RT) for athletes may be difficult during some training-phases due to competing demands. However, it is currently unknown how strength and conditioning coaches prescribe RT during periods of planned de-loading. Therefore, we aimed to investigate the RT prescription practices of coaches during four common de-loading periods (taper, competitive season, tournament, travel). METHODS An anonymous online survey was shared globally to coaches, with data analysed from 204 responders (current level of athlete coached: world class n=68, elite/international n=62, highly-trained n=64, trained n=10). Coaches only provided answers about prescription for de-loading periods which they reported encountering. Where a coach indicated not prescribing RT for specific de-loading periods, they provided information on any barriers preventing RT prescription. RESULTS Weekly RT prescription across all de-load periods was typically reported as: 1-2 sessions, 30-60 min, 1-3 sets, 1-6 repetitions. Most coaches reported decreasing volume during all periods (taper: 89.1%, competitive season: 70.4%, tournament: 84.1%, travel: 74.6%), with the most common reduction in RT volume reported as 0-25%. Most coaches also decreased intensity during a taper (52.9%), tournament (54.8%) and travel (53.6%), with a 0-25% reduction most common. ‘Lack of equipment and facilities’ and ‘scheduling/time’ were common barriers cited to RT prescription during the competitive season (100% for scheduling/time), tournament (55.6% and 50.0%), and travel (57.3% and 60.0%). During a taper, ‘recovery’ was the most reported reason (41.7%). CONCLUSION During planned de-loading periods, both training volume and intensity are generally decreased by coaches compared to periods of normal training. The similarity of barriers to RT prescription during de-load periods suggests the experiences of coaches are not influenced by the phase. To address barriers experienced by some coaches, researchers should examine the use of alternative RT strategies for periods of planned de-loading to maintain training stimulus.

Assessment of Masseter Volume and Postoperative Stability After Orthognathic Surgery in Patients With Skeletal Class III Malocclusion With Facial Asymmetry.

This study aimed to evaluate the effect of orthognathic surgery on masseter volume in patients with skeletal Class III malocclusion with facial asymmetry and the effect of masseter volume on stability in orthognathic surgery. This research studied 16 patients with Class III malocclusion with facial asymmetry who received combined orthodontic-orthognathic treatment and underwent craniofacial computed tomography (CT) before (T0), 2 weeks after (T1), and 6 months after (T2) surgery. Three-dimensional (3D) CT images were retrospectively analyzed, using 3D volume reconstruction to obtain the masseter volume and examine the impact of the masseter volume on stability in orthognathic surgery. A statistically significant difference (P < 0.05) in the volume of the masseter was found up to 6 months after orthognathic surgery compared with the preoperative period, and the reduction in the masticatory muscle volume on the lengthened side is greater than on the shortened side (P < 0.05). The volume of both masseters differed according to facial asymmetry, and the difference was significantly reduced after orthognathic surgery (P < 0.05). During the period time (T1-T2), cephalometric maxillary marker points were not significantly different (P > 0.05), and mandibular marker points were significantly anteriorly shifted (P < 0.05). There was an association between the masseter volume and anterior shift of point B (R > 0.5, P < 0.05), the upward and anterior shifts of the gonion point differed between the lengthened and shortened sides (P < 0.05). The size of the masseter becomes smaller 6 months after orthognathic surgery, and orthognathic surgery improves both bone and soft tissue symmetry. A larger sagittal relapse of mandibular setback occurred in patients with greater masseter volume. Considering these alterations may be helpful in planning orthognathic surgery.

STATE OF ECONOMIC SECURITY AND DIRECTIONS OF RESTORATION SOCIO-ECONOMIC DEVELOPMENT AND FOOD SECURITY IN THE CONDITIONS OF WAR

The purpose of the article is to determine the state of economic security, ways to ensure its level, and ways to restore socio-economic development under the cumulative impact of threats. In order to realize this goal, an expert assessment of the components of economic security provided and the need to take into account the component of military-economic security indicated. It indicated that the task of neutralizing threats to military and economic security opens up new windows of opportunity, in particular opportunities in ensuring socio-economic development. Prerequisites for the use of opportunity windows are defined. The dynamic nature of threats of war that require institutional measures for permanent monitoring of dynamic threats, their operational analytical assessment and the introduction of tactics to neutralize threats and reduce their long-term negative impact, are indicated. An analysis of the state economic security provided, directions for improving this state by components of economic security indicated. The main factors on which the well-being of the country's population depends are determined, the effects of crises on the indicators of the levels of income and expenditure of the population analyzed, and the drivers of the deterioration of well-being are established. It noted that the deterioration of the socio-economic situation of households led to the narrowing of the domestic market, which had a negative impact on the functioning of SMEs. It indicated that this created a negative inverse multiplier effect on the well-being of the population. The negative effects of the crisis, which led to a reduction in production volumes in the agricultural sector, were identified. It indicated that this significantly limited the ability of the branch to fulfil food security tasks. Proposed ways to reduce the negative impact of war on agricultural production to ensure food security.  The directions and recommendations for economic and food security and restoring socio-economic development are specified.

Immunotherapy in the Management of Sinonasal Mucosal Melanoma: A Systematic Review.

The aim of this work is to comprehensively review and synthesize the literature related to sinonasal mucosal melanoma (SNMM) treatment with immunotherapy, including potentially targetable genetic mutations, survival outcomes, and adverse events. Embase, Cochrane, Scopus, and Web of Science. The study protocol was designed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Databases were searched from inception through May 23, 2023. A total of 42 studies met inclusion criteria. Twenty-four of the included studies reported genetic mutations for a combined 787 patients with SNMM. 8.1% (95% confidence interval, CI: 7.6-8.6), 18.9% (95% CI: 18.1-19.8), and 8.5% (95% CI: 8.1-9.0) of reported patients were positive for BRAF, NRAS, and KIT mutations, respectively. The presence of brisk tumor-infiltrating lymphocytes was associated with improved recurrence-free survival and overall survival (OS). Six studies reported a combined 5-year OS after adjuvant immunotherapy treatment of 42.6% (95% CI: 39.4-45.8). Thirteen studies encompassing 117 patients reported adjuvant or salvage immune checkpoint inhibitor (ICI) immunotherapy response rates: 40.2% (95% CI: 36.8-43.6) had a positive response (tumor volume reduction or resolution). Eleven studies reported direct comparisons between SNMM patients treated with or without immunotherapy; the majority (7/11) reported survival benefit for their entire cohort or select subgroups of SNMM patients. With the transition to modern ICIs, there is a stronger trend toward survival improvement with adjuvant ICI. Tumors with Ki67 <40% may respond better to ICI's. ICI therapy can be an effective in select SNMM patients, especially those with advanced/metastatic disease.

Carbon Reduction Impact from Synchronising PrescriptionS (CRISPS): A pilot study

Abstract Introduction Synchronising the dates of patients’ repeat prescriptions can reduce monthly community pharmacy visits or home deliveries, which may improve patients’ adherence to medicines.[1] It should also reduce carbon dioxide (CO2) emissions associated with avoidable travel, but previous research does not appear to have determined the potential size of this reduction. This pilot study therefore attempted to do so using routinely collected data. Aim To estimate potential carbon savings from synchronising repeat medicines for a sample of patients from one community pharmacy. Methods All patients who had prescriptions dispensed four times per month or more from a single medium-sized (approximately 2,500 items dispensed per month) urban community pharmacy in England were identified from the pharmacy’s home delivery application. The threshold of four deliveries per month was selected to increase the likelihood of this frequency being due to asynchronised prescriptions. Data were collected (August 2023) for deliveries in June 2023 as there were no public holidays or events to affect prescription ordering. Data included patients’ postcode, delivery dates, and using the Patient Medication Record, the pharmacist collecting the data determined acute or one-off prescription items, that neither the patients nor the repeat medicines were new, and where deliveries were made to supply medicines owing. The pharmacy was selected because it efficiently managed stock to minimise items owing. The distance that would have been travelled was calculated as if the medicines had been collected from the pharmacy as a dedicated journey to and from the patient’s home address instead of being delivered. The saving in miles and CO2 emitted for different vehicle types was modelled by assuming that for each patient, all deliveries that were not for acute items or medicines owing could have been reduced to a single delivery if prescriptions had been synchronised. UK Government conversion factors were used to calculate CO2 emissions.[2] Results Data were collected for 59 patients, of whom 7 patients had 8 deliveries, 4 had 7 deliveries, 6 had 6 deliveries, 16 had 5 deliveries and 26 had 4 deliveries. The total number of deliveries to these patients was 269 but would have been 80 deliveries if the repeat prescriptions had been synchronised (70% reduction). The distance travelled would have been reduced from 842 miles to 241 miles (71% reduction). This would have resulted in a 71% reduction in CO2 emissions, although the reduction in volume in kilograms of CO2 emitted would have varied (by an estimated 137 Kg CO2 or 51%) depending on whether e.g., a small diesel car was used or a large petrol car (reduction of 133kg versus 270 kg CO2). An average diesel car was estimated to have reduced CO2 emissions by 163 kg. Conclusion The findings demonstrate that potential carbon savings from medicines synchronisation can be modelled from routinely collected data, but with limited accuracy, especially as patients receiving home deliveries may not be representative of all pharmacy users. Challenges remain in how to measure actual carbon savings of prescription synchronisation and overcoming barriers to widespread implementation of clinically appropriate synchronisation.

Efficacy of Phlogenzyme® in men following transurethral laser enucleation of prostate hyperplasia: results of a randomized trial

Introduction. The most advanced and effective method of surgical treatment for benign prostatic hyperplasia (BPH) is transurethral laser enucleation of the prostate (tLEP). Recently, there has been a growing interest in exploring new approaches to reduce the risk of complications following tLEP.Objective. To evaluate the efficacy of using Phlogenzym® as part of a comprehensive treatment plan for patients following tLEP to reduce dysuria (urinary discomfort), leukocyturia (white blood cells in urine), and prevent infectious and fibrosis-related complications.Materials &amp; methods. An open-label, randomized trial enrolled 105 patients undergoing tLEP. The patients were randomly assigned to two groups: the study group (n=50) received standard postoperative care in combination with Phlogenzym® for 30 days, while the control group (n=55) received standard care (α1-adrenergic blocker for 28 days) only. uring the follow-up period, which lasted for 1, 3, and 6 months postoperatively, complaints were evaluated using the IPSS-QoL, and IIEF-5 questionnaires, as well as indicators of urinalysis and urine culture, prostate volume measurements, residual urine volume, and uroflowmetry data.Results. Among all patients, the median preoperative values for prostate volume, IPSS, QoL score, and median peak urine flow rate were 90 cc, 18 points, 5 points, and 7.9 mL/s, respectively, with no significant differences between the groups. One month after surgery, in the study group, there was a more significant decrease in prostate volume (57% vs. 41%), although this difference was not statistically significant (p &gt; 0.05). At the 6-month follow-up, bacteriuria was less common in the study group (42% vs. 67%), and there was a consistent trend toward a reduction in the incidence of fibrous complications, although these differences were not statistically significant either (p &gt; 0.05). No adverse events occurred during the follow-up period.Conclusion. Our experience suggests that the use of Phlogenzym® is safe during the postoperative period following tLEP surgery. The use of this drug leads to a reduction in prostate volume postoperatively and significantly reduces the bacteriuria by the six-month follow-up. Additionally, there is a persistent positive trend towards reducing the overall incidence of fibrotic complications in the surgical site. The results achieved and the absence of significant side effects characterize Phlogenzym® as having a favorable clinical profile.

Inhibition of asparagine synthetase effectively retards polycystic kidney disease progression.

Polycystic kidney disease (PKD) is a genetic disorder characterized by bilateral cyst formation. We showed that PKD cells and kidneys display metabolic alterations, including the Warburg effect and glutaminolysis, sustained in vitro by the enzyme asparagine synthetase (ASNS). Here, we used antisense oligonucleotides (ASO) against Asns in orthologous and slowly progressive PKD murine models and show that treatment leads to a drastic reduction of total kidney volume (measured by MRI) and a prominent rescue of renal function in the mouse. Mechanistically, the upregulation of an ATF4-ASNS axis in PKD is driven by the amino acid response (AAR) branch of the integrated stress response (ISR). Metabolic profiling of PKD or control kidneys treated with Asns-ASO or Scr-ASO revealed major changes in the mutants, several of which are rescued by Asns silencing in vivo. Indeed, ASNS drives glutamine-dependent de novo pyrimidine synthesis and proliferation in cystic epithelia. Notably, while several metabolic pathways were completely corrected by Asns-ASO, glycolysis was only partially restored. Accordingly, combining the glycolytic inhibitor 2DG with Asns-ASO further improved efficacy. Our studies identify a new therapeutic target and novel metabolic vulnerabilities in PKD.

On the accuracy of saturation estimation from electrical measurements of soils with high swelling clay content

AbstractElectrical conductivity models have been widely used to estimate water content and petrophysical properties of soils in hydrogeophysical studies. However, these models are typically only valid for soils with non‐expandable matrices because they were originally developed for clean sandstone reservoir rocks. Soils containing swelling clays are characterized by matrices that expand/contract upon gaining/losing water. In this laboratory study, we demonstrate that soil matrix changes affect saturation estimation using Archie's laws. A sample of a soil containing a swelling clay was fully saturated with a potassium chloride solution, then left to dry evaporatively at room temperature for 8 days. The complex resistivity of the soil, along with its weight and volume shrinkage, were measured daily during the drying period, and the surface conductivity was calculated based on previous empirical findings. Over the course of the study, the simultaneous evaporation yielded a 33% decrease in volume and caused a nonlinear reduction in saturation with decreasing water content. Accounting for surface conductivity and correcting for saturation using the calculated volume reduction resulted in a power‐law relationship with high R2 values between resistivity and saturation along with reasonable saturation exponents. On the contrary, neglecting either surface conductivity or shrinkage caused similar underestimations of saturation exponents. These results indicate that the application of Archie's second law to soils with swelling clays leads to erroneous predictions of resistivity if saturation values are not corrected for changes in the volume of the soil and surface conductivity is neglected.