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In the present study, bacterial endophytes were obtained from weeds of potato fields. Their antagonistic activity was screened against potato storage pathogen, Pectobacterium carotovorum subsp. carotovorum (Pcc) (JX029052), in the maceration assay. An endophytic strain, PC-2B was isolated from Convolvulus arvensis L. as a dominant weed of potato fields. In vivo application of this strain led to 58.8% reduction in tuber decay. This motile strain that can produce amylase was identified as Pantoea sp. using phenotypic features and 16S rRNA sequencing. Following PC-2B treatment, 56.7% Reduction in Disease Incidence (RDI) was obtained in preventative and 52% in curative challenges under semi-practical storage trails. Anti-Pcc bioactive compounds of Pantoea sp. was extracted and identified based on H NMR and FT-IR techniques. Two peptide antibiotics including Pantocin A and B with inhibitory effect against Pcc were characterized. These results might indicate that the tested Pantoea strain could be a promising candidate to protect potato tubers against soft rot disease caused by Pcc. However, large-scale complementary trials have to be conducted to validate these results before any recommendations. [ABSTRACT FROM AUTHOR]

SBRT is a standard of care treatment for localized prostate cancer. Intra-prostatic boost (IPB) may improve biochemical control. Additionally, the prognostic impact of early PSA nadir has been described by ICECaP collaborative. In the present series, we report early PSA kinetics for patients with intermediate risk disease who received IPB treated with SBRT with and without short course of hormone therapy. From October 2018 to June 2023, 280 patients with intermediate risk prostate cancer were treated with a robotic stereotactic body radiotherapy platform with fiducial tracking. Intra-prostatic nodules were delineated using diagnostic and treatment planning MRI by the treating radiation oncologist. Patients received the standard dose of 36.25Gy to the prostate and proximal seminal vesicles with isotropic expansion margin of 5mm, except posteriorly towards the rectum, where the margin was 3mm. GTV received 40 Gy. For assessing PSA kinetics, each patient's PSA value at diagnosis and follow-up, defined as 6-12 months after completion of treatment, were considered. PSA values were retrospectively extracted from each patient's medical records and the percentage of patients with PSA values <0.1 ng/mL, <0.2 ng/mL, and <0.5 ng/mL within 6-12 months of completion of treatment was determined. Patients were compared based on the use of short term (4-6 months) hormone therapy with SBRT. Of 280 patients, 157 patients received hormone therapy and 123 did not. The median and ranges of PSA values at diagnosis for each group were 6.9 (0.8-19.5) and 6.8 (2-19.9), respectively. Of patients who received hormone therapy with SBRT and IPB, 36.9% achieved PSA<0.1ng/mL compared to 1.6% for those who did not receive hormone therapy. Respectively, 58.0% and 4.1% achieved PSA<0.2mg/mL and 86.0% and 15.4% achieved PSA<0.5ng/mL within 12 months of treatment completion. SBRT is a safe and effective treatment for patients with localized prostate cancer. To our knowledge, this report is the largest series describing early PSA kinetics for patients treated with SBRT with IPB in the context of established PSA nadirs reported by ICECaP collaborative group. Long-term follow up is needed to determine the prognostic significance of these findings. [ABSTRACT FROM AUTHOR]

SBRT is an emerging treatment for patients with RCC who are not surgical candidates. Pooled analysis of an international consortium suggests promising short term local control. In the event of local failure, other ablative methods may be used to salvage these patients. Trends in radiographic surveillance are not well characterized post SBRT. In this study we observe a common transient increase in the tumor size followed by stability or decline in patients treated with fractionated SBRT on a phase II clinical protocol. Radiographic studies of patients enrolled in a phase II clinical trial were reviewed for this report. Primary RCC tumors were treated using SBRT with two fractionation schema (48 Gy in 3 or 4 fractions) based on a 5 cm size threshold. Patients were followed with routine imaging per protocol at 3, 6, 12, 18, and 24 months post-treatment. Percent change in greatest dimension is analyzed over time and subsequently stratified by dose, baseline tumor diameter, and PTV. An increase in tumor size by 10% or greater followed by tumor shrinkage or stability was considered a transient increase. From August of 2013 to December of 2022, 40 patients were enrolled in this trial with a median age of 77.5 and follow up of 18 months. 32 patients with at least two follow up images (minimum of 6 months post-SBRT) were included in the analysis. 26 of these patients were treated with 48 Gy in 3 fractions and 6 were treated with 48 Gy in 3 fractions. Median tumor size was 38.4 cc with a median diameter of 3.5 cm. 46.9% of patients experienced a transient increase with a median increase of 19.7% (range = 63.1, IQR = 13.9%-38.6%) of the pretreatment largest dimension. 66.7% of patients with tumors ≥ 5 cm experienced a transient increase vs. 42.3% of patients with tumors < 5cm. 56.3% of patients with PTV ≥ 38.4 cc experienced a transient increase vs. 40% of patients with a PTV < 38.4cc. Patients with PTV < 38.4 cc experienced a median 19% increase compared with the PTV ≥ 38.4 cc median increase of 37.5%. Most common transient increase was observed at 3 months post treatment. Of patients evaluated with CT scans, 50% experienced a transient increase, compared with 37.5% of those evaluated with MRI scans. SBRT is a promising treatment for primary RCC, however radiographic surveillance of the disease post-treatment is not well characterized. In this study of patients enrolled in a Phase II protocol, there appears to be a transient radiographic increase in the size of primary tumors followed by stability and decline. Further investigations will guide the timing and need for salvage treatment for post- SBRT RCC. [ABSTRACT FROM AUTHOR]

Background. Nordic hamstring test is a field-based test to estimate the hamstrings' injury risk. The aim of this study was to investigate the relationship between Nordic hamstring test and isokinetic dynamometry in football and track and field student athletes. Methods. Knee flexor eccentric peak torque of hamstring, optimum length, and muscle balance indices were obtained in two seated and lying positions in 22 footballs and 22 track and field student athletes. The Nordic break point angle was also measured. Results. There were significant correlations between isokinetic dynamometry indices and breakpoint angles (P=0.000). Best predictors of break point angle were muscle balance indices and eccentric hamstring peak torques in lying position (P < 0.05). Conclusions. It seems that Nordic hamstring test is related to isokinetic dynamometry. This relationship is also dependent on the hip joint positioning. These findings may have implications in the assessment of athletic performance. [ABSTRACT FROM AUTHOR]

Platinum containing sulfated zirconia (Pt-SZ/Al) catalyst was prepared by precipitation method. Characterization of the prepared catalyst was performed using XRD and SEM, and catalytic activity was studied for isomerization of nC5 at atmospheric conditions and temperatures of 180-240°C in a ow reactor. The effects of reaction temperature, H2/nC5 ratio, and WHSV were investigated. As revealed by SEM and XRD, the prepared sulfated zirconia was of nanoscale size and had predominantly tetragonal crystalline phase. n-pentane conversion increased with increasing temperature and selectivity decreased. The optimal reaction temperature was 220°C where n-pentane conversion and isopentane selectivity were 70% and 94%, respectively. The positive effect of H2/nC5 ratio was observed on nC5 conversion and iC5 selectivity in the investigated H2/nC5 ratio range. This trend of variation was related to the role of acid and metallic sites on the reaction pathway. As expected, increase in the WHSV, which reduces contact time between reactant and catalyst, decreased nC5 conversion and increased selectivity toward iC5. The RON of the product increased with increasing temperature; then, it showed slight decrease at higher temperature. The decrease in the activation energy was observed, which can be attributed to the different reaction mechanisms or different rate-determining steps. [ABSTRACT FROM AUTHOR]

Objective: Lipid oxidation and generation of free radicals are important factors contributing to the formation of atherosclerotic plaque. Bilirubin is supposed to play a protective role against atherosclerosis, coronary artery diseases (CAD) and inflammation for its strong antioxidant property. Thus, this study aims at investigating the relationship of bilirubin level with the severity and type of coronary artery stenosis (CAS) in different patient groups. Materials and Methods: In this cross-sectional study 200 consecutive patients, who underwent elective angiography in Madani Heart hospital, Tabriz, Iran, were selected and their blood samples were measured for total, direct, and indirect bilirubin level, with Diazo method using colorimetric technique. Following angiography, comparisons were made between the severity and location of CAS and therapeutic follow-up plan with total, direct, and indirect bilirubin level. Results: Of 200 studied patients, 129 (64.5%) and 71 (35.5%) subjects were male and female, respectively. The cases were classified into 5 subgroups based on angiography results as follows: 59 (29.5%) cases with normal angiography, 11 cases (5.5%) with minimal CAD, 56 cases (28%) with single vessel involvement, 35 (17.5%) cases with two vessel involvement and 39 cases (19.5%) with three vessel involvement. The mean total bilirubin level was 1.47 ± 0.8 mg/dl, 1.27 ± 0.12 mg/dl, 1.27 ± 0.06 mg/dl, 1.6 ± 0.04 mg/dl and 0.98 ± 0.05 mg/dl, respectively for the cases with above order. The mean difference in serum total bilirubin between normal angiography group and three-vessel involvement group was 0.49 mg/dl (P < .0001). There was a significant inverse relation between bilirubin level (total, direct and indirect) and number of involved vessels and involvement intensity increased as serum bilirubin level decreased. Severity of coronary arteries stenosis as well as the number of involved vessels increased as serum bilirubin level decreased. Conclusion: According to results, there was a significant inverse relation between serum bilirubin level and coronary involvement (type and intensity). Higher bilirubin serum levels played a protective role against CAD, even in the presence of other risk factors. Therefore, bilirubin level can be used as a predictor of CAD in the future.

SBRT is a standard of care treatment for localized prostate cancer. Clinical trials have shown excellent biochemical control in patients who are treated with conventional radiation with a concomitant IPB. Dose escalation to the whole gland may lead to unacceptable toxicity, however the role of IPB to a dominant nodule using SBRT is yet to be determined. In this report, we describe urethral and bladder dosimetric parameters for patients receiving SBRT with IPB and compare them to a cohort of patients treated without IPB. From October 2018 to June 2023, 443 patients were treated with a robotic SBRT platform to the whole gland with fiducial tracking with IPB (cohort A). Nodules were delineated using diagnostic and treatment planning MRI. Patients received the standard dose of 36.25Gy to the prostate and proximal seminal vesicles with isotropic expansion margin of 5mm, except posteriorly towards the rectum (PTV) and 40 Gy to GTV. Urethra was delineated using contrast-enhanced suprapubic urethrogram. Institutional dose constraints were utilized for evaluation of treatment plans. For the comparison cohort (cohort B), 97 patients treated with the same parameters without IPB, from February 2021 to August 2022, were used. Dosimetric data was retrospectively extracted from the treatment planning software and compared between the two cohorts. Using a programming environment, Wilcoxon rank-sum test was used to test the hypothesis of an increase in median value from cohort B to cohort A. In cohort A, all patients had at least one nodule, while 70 had two, and 13 had three or more, for a total 540 nodules with a median volume of 0.73cc (0.05cc-10.1cc) and median D90% of 42.8 Gy. Prostate volume medians and ranges for cohorts A and B were 32.9cc (12.0cc-142.2cc) and 46.4cc (18.7cc - 122.8cc), respectively. Median values of dosimetric parameters are summarized in the accompanying table. No statistically significant increase in median doses from B to A were observed. When comparing nodule size and urethral dose for cohort A, no correlation was found between intra-prostatic nodule size and urethral D0.03cc (R-value = 0.08). SBRT is a safe and effective standard of care for localized prostate cancer, however questions remain regarding the role of dose escalation with extreme hypofractionation. Here we report on a large cohort of patients treated with IPB with strict adherence to institutional dose constraints. When comparing key dosimetric parameters, receiving IPB did not lead to higher doses to the urethra and bladder. Long-term follow-up and randomized protocols are needed to confirm the safety and efficacy of this approach. [ABSTRACT FROM AUTHOR]

SBRT is a standard of care treatment for localized prostate cancer. Dose escalation improves outcomes for prostate cancer and concomitant intraprostatic boost (IPB) may offer an acceptable approach for dose escalation while maintaining tolerable dose to organs at risk. In this series, we report changes in IPSS score over a 12-month period following SBRT with IPB in patients treated in at a single academic institution with routine collection of pre- and post-treatment IPSS surveys. Eighty-one patients treated from October 2018 to March 2022 received robotic stereotactic body radiotherapy with fiducial tracking and completed IPSS questionnaires. IPSS scores were evaluated for patients at three time points: pre-treatment, post-treatment, defined as 3 months after SBRT completion, and at follow-up, defined as within 12 months after SBRT completion. Patients who experienced minimally important difference (MID) in their post-treatment IPSS score comprised cohort A and those who did not comprised cohort B. Critical urethral and bladder doses were retrospectively extracted from the treatment planning software. Using a programming environment, two sided, two-sample t-tests were performed to compare dosimetric parameters between the two cohorts. Of the 81 total patients, 47 experienced MID. For cohort A, IPSS score medians and ranges were 8 (0-29), 6 (1-19), and 6.5 (0-31) for pre-treatment, post-treatment, and at 12-month follow-up, respectively. For cohort B, the medians and ranges were 5 (0-21), 12 (5-28), and 8.5 (1-32), respectively. A summary of median dosimetric parameters for each cohort is shown in the accompanying table. Max dose to (D0.03cc) to bladder was the only statistically different dosimetric parameter between the cohorts. IPB is well tolerated with minimal change in urinary quality of life metrics as measured by IPSS. Max dose to the bladder remains the only significant difference in patients who experienced MID in their quality of life. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Socially disadvantaged populations in the United States experience worse outcomes compared to the general population when diagnosed with breast cancer. One potentially vulnerable population includes patients under age 65 that qualify for Medicare due to debilitation. This group includes patients who have received social security disability insurance for at least 2 years and those who have been diagnosed with end-stage renal disease or amyotrophic lateral sclerosis; current literature suggests this population experiences worse oncologic outcomes. The National Cancer Database (NCDB) was analyzed to determine what factors among patients under the age of 65 who qualify for Medicare predict for a higher likelihood of presenting with stage IV breast cancer.Materials/methods: The NCDB was queried for breast cancer patients diagnosed from 2004-2014 who were below the age of 65 and qualified for Medicare. Patients were excluded if they presented with noninvasive disease or if their AJCC stage was unknown. Patients were excluded if any social determinants (race, income quartiles, Charlson-Deyo comorbidity score, travel distance) or hospital factors (facility type, facility location) were unknown. Pearson chi-square test was used to identify associations between categorial variables and stage. Univariate analysis of sociodemographic factors was performed. Statistically significant factors were included in a multinomial logistic regression model to determine independent covariates associated with stage IV presentation.Results: 56,964 patients met study criteria. Based on P values (P < 0.05) and strength of odds ratios, the following variables were included in the final model: race, income, comorbidity score, travel distance, facility type, and facility location. All covariates except facility location and distance were significant predictors of metastatic disease presentation. Race was a significant predictor, with white patients less likely to have stage IV presentation (OR 0.73, P < 0.001) compared to black patients. Individuals earning < $38,000 annually were significantly more likely to present at stage IV (OR 1.15, P < 0.001). Patients who traveled shorter distances to treatment facility had non-significantly higher odds of presenting at stage IV (OR 1.37, P = 0.608). Higher comorbidity score was a significant predictor of Stage IV disease at presentation.Conclusion: Multiple sociodemographic factors were powerful predictors of a stage IV breast cancer presentation in this select population of patients under 65 years old who qualify for Medicare due to debilitation. A deeper understanding of these factors can help identify patients at high risk of a metastatic cancer presentation in order to provide screening and preventative services at an earlier stage in this vulnerable population. [ABSTRACT FROM AUTHOR]

Cancer control outcomes are significantly worse in obese prostate cancer patients. Over the past decade, stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for localized prostate cancer. Accurate delivery of external beam radiation could be adversely affected by increased pelvic adipose tissue and result in worse biochemical control. Data reporting on the efficacy of SBRT stratified by BMI is limited. This single-institution study sought to evaluate oncologic outcomes following SBRT for prostate cancer in men based on BMI. A retrospective chart review was performed on all patients with localized prostate cancer treated with SBRT at a single institution between 2006 to 2021. Treatment was delivered using robotic SBRT with doses of 35-36.25 Gy in 5 fractions, per institutional protocol. Biochemical recurrence was defined by the Phoenix definition (PSA rise ≥ 2 ng/mL above nadir). Multiple regression Cox proportional hazard analysis was performed. 1306 patients were identified, with a mean follow-up of 47 months. The patients were elderly (Median age = 70 years) and overweight (Median BMI = 27.6 kg/m2). The majority were low to intermediate risk (88%) according to the D'Amico classification. Median pre-treatment PSA was 7.4 ng/mL. 23.7% received neoadjuvant ADT. BMI (kg/m2) was calculated prior to initiation of treatment and patients were stratified as thus: BMI < 25, 25 – 29.9, 30 – 34.9, ≥ 35. There was no statistically significant difference between pre-treatment PSA or Gleason's score between BMI groups. A multiple regression Cox proportional hazard analysis was performed, with BMI < 25 set as the reference. There was no statistically significant difference in biochemical disease-free survival, distant metastasis-free survival, or disease-specific survival between BMI subgroups. In the general population, cancer control following prostate SBRT is equivalent to other standard radiation options. In this analysis, increased BMI did not portend worse oncologic outcomes following SBRT when analyzing bDFS, DMFS, or DSS. Thus, in the opinion of the authors, obesity should not be considered a contraindication to prostate SBRT. [ABSTRACT FROM AUTHOR]

Outcomes following accelerated partial breast irradiation in select women with early-stage breast cancer are comparable to whole breast irradiation. ASBRT is an attractive treatment option, but mature toxicity outcomes are limited. Toxicity risk with SBRT has been associated with a consecutive daily schedule in other organs. In the present study, we explore the association of treatment schedule and fat necrosis. Early-stage breast cancer patients (Stage 0 and I) were treated per an institutional protocol. A minimum of 4 gold fiducials were implanted around the lumpectomy cavity for target delineation and tracking. The clinical treatment volume (CTV) was defined as lumpectomy cavity with a uniform 0-10 mm expansion confined to breast tissue. The planning treatment volume (PTV), defined as the CTV with a 0-2 mm uniform expansion, was prescribed 30 Gy in 5 fractions. Breast examination and mammography were completed per routine institutional practice. A patient was deemed to have fat necrosis when breast examination identified a tumor bed mass with distinctive mammographic characteristics. Twenty women were treated over a 7-year period extending from September 2008 to September 2015 and followed for a minimum of 6 years. The median CTV expansion was 5 mm (range, 0-10), median PTV was 62.5 cm3 (range 15-142), median PTV/breast volume ratio was 8.3% (range 4.1-25.6), median prescription isodose line was 83% (range 75-87) and median treatment duration was 7 days (range 5-13). Seven patients were treated on 5 consecutive days (i.e., Monday through Friday). At a median follow up of 8 years (range, 6-12 years), 5 women developed fat necrosis. All 4 symptomatic patients had been treated on consecutive days and the symptomatic fat necrosis was diagnosed at a median follow-up of 5.9 years (range, 4.8-7.4). Cox regression analysis identified consecutive daily treatments as a predictor of symptomatic fat necrosis (OR: 26.8, p value =0.05). Our mature findings demonstrate an association between Monday through Friday treatment and symptomatic fat necrosis. Fortunately, our research also suggests that symptomatic fat necrosis is curtailed by merely extending the treatment duration beyond 5 days. Accordingly, we believe that the Fast-Forward trial investigators should reevaluate their current assertion that 26 Gy whole breast irradiation delivered in 5 consecutive daily fractions over 5 or 7 days is a new standard treatment option. Only the yet to be completed 10-year analysis of this large prospective study will ultimately determine if delivering 5 large consecutive daily adjuvant breast radiation treatments is associated with symptomatic fat necrosis and if adding 2 additional days to the treatment course effectively curtails this adverse side-effect. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Following definitive treatment for localized prostate cancer a subset of men will unfortunately develop recurrent disease. Newer PET agents have demonstrated that most early recurrences occur in the abdominopelvic nodal basins. The optimal treatment strategy for this patient population is unknown but likely includes a combination of systemic therapy, surgery and/or radiation therapy. For radiation therapy, the optimal treatment volume, fractionation schedule and dose remain unanswered questions. We report early outcomes for patients treated with involved field SBRT for nodal oligo-recurrent prostate cancer.Materials/methods: Between January 2018 and January 2020, 21 patients with nodal oligo-recurrent prostate cancer treated with involved field SBRT at a single academic institution were eligible for inclusion in this analysis. Detection of recurrence was ascertained by imaging including: Axumin PET/CT (66%) or MRI/CT (34%) following a PSA rise. All patients were treated with five-fraction involved field SBRT to a dose of 27.5-30 Gy. The treatment volume for involved field was defined as the nodal basin containing the gross nodal disease as well as the immediately adjacent nodal basins. Oligo-recurrence was defined as any volume of disease that could be safely treated within an involved field. Acute and late toxicity data was defined as any treatment related toxicity occurring ≤ 90 days and > 90 days following treatment, respectively. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4.0. PSA response was defined as any decrease in the PSA following treatment. Local recurrence was defined as any new or growing lesion within the treatment field following treatment. Local control was calculated using the Kaplan-Meier method.Results: The median pre-salvage PSA was 7.2 ng/ml. The median follow-up for all patients was 25 months (11 - 36 months). The most common acute side effect was grade 1 diarrhea (n = 7, 33%). Acute grade 2 GI toxicity occurred in 14% of patients (n = 3). Two patients had late low grade pelvic pain and 1 patient had late grade 2 lower extremity limb edema. There were no late grade 2+ GI side effects. No grade 3+ side effects occurred at any time following treatment. 88% of patients had a PSA response following treatment. The local control at 1 and 2 years was 100% and 94%, respectively.Conclusion: With the widespread adoption of novel PET agents the group of patients with oligo-recurrent nodal disease is likely to increase significantly. The optimal combination of local and systemic therapy in this patient population is the subject of ongoing clinical investigation. With a favorable toxicity profile, high rates of local control and PSA response, involved field SBRT represents a feasible as well as convenient local therapy treatment option for an elderly patient population. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Definitive chemoradiation is standard-of-care treatment for locally advanced inoperable non-small cell lung cancer (NSCLC). However, some patients refuse radiation therapy (RT) and this information is captured in the National Cancer Database (NCDB). We sought to examine factors associated with patient refusal of RT recommended for clinical stage III NSCLC and to evaluate subsequent outcomes compared to standard treatment.Materials/methods: The NCDB (2004-2015) was queried for clinical stage III NSCLC patients who were recommended definitive chemoradiation. We then selected cases in which RT was given or was recommended but refused "by the patient, patient's family member or guardian." We excluded patients with: unknown treatment modality/sequence, those who did not undergo RT for unknown reasons, and those initially not recommended RT. Survival of patients who received RT vs. those who refused RT was compared using log rank test in Kaplan Meier curves. Univariate and multivariate Cox regression were performed to identify predictors of refusal of RT and relationships between each covariate and survival.Results: We identified 147,314 patients recommended RT for clinical stage III NSCLC. 141,668 patients underwent definitive treatment with RT and 5,646 (3.8%) refused the recommended RT. On multivariate analysis, older age, female sex, lack of insurance or Medicare/Medicaid insurance, lower income, and higher comorbidity score all significantly predicted refusal of RT. 11.5% (n = 649) of the patients who refused RT were treated with chemotherapy alone. Median survival was significantly worse for patients who refused RT versus those who received RT (5.7 months vs 14.7 months, P < 0.0001) and refusal of RT was predictive of death (HR 1.63, P < 0.0001). 18.2% of patients who received RT were treated to a palliative dose, defined as ≤ 4500 cGY. < 1% of all patients received immunotherapy, and this was associated with improved median survival as well, 14 vs. 20.1 months (P < 0.0001).Conclusion: While the vast majority of locally advanced NSCLC patients are amenable to proceeding with standard treatment, refusal of RT when recommended comes at the cost of inferior survival in this unadjusted cohort from a large hospital-based national database. Sociodemographic factors appear to be associated with refusal of standard of care treatment. These should be further explored to eliminate disparities in the treatment of inoperable but potentially curable NSCLC. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Postoperative radiation (PORT) is recommended by consensus guidelines for incompletely resected stage II-III non-small cell lung cancer (NSCLC) to optimize local control. Prior data across disease sites has suggested disparities exist in receipt of beneficial adjuvant therapies based on sociodemographic barriers including geography. We sought to explore if receipt of PORT in margin positive locally advanced NSCLC was related to travel distance from the treating facility.Materials/methods: We identified patients with pathologic stage II-III NSCLC within the National Cancer Data Base who underwent treatment with upfront surgery (lobectomy or pneumonectomy) found to have microscopic (R1) or macroscopic (R2) residual tumor. Only patients coded as receiving adjuvant external-beam PORT (50-74 Gy) or no radiation were included. Multivariable logistic regression was utilized to determine factors associated with PORT receipt. Cox regression was used to identify predictors of survival.Results: We identified 7,270 pathologic stage II-III NSCLC patients who underwent R1/R2 resections from 2004-2015; of these, 36% received PORT. Median overall survival in these patients was significantly improved with the addition of PORT, from 22.3 months to 32.8 months and this persisted when stratified by distance traveled (see table 1). Of the patients who did not receive PORT, 43.4% did receive adjuvant chemotherapy and < 1% received immunotherapy. Reason for why PORT was not given was largely unknown, but stated reasons included: contraindicated due to risk factors (3.6%) and patient refusal (4.2%). In contrast, 79.1% of PORT patients also received chemotherapy. Half of PORT patients resided within 10 miles of treatment facility. Progressively father travel distance was associated with decreased likelihood of PORT (OR 0.89, P = 0.002). Other factors associated with decreased PORT receipt included older age and decreased level of education. On Cox regression, higher co-morbidity score was predictive of death, while receipt of PORT was protective (HR 0.87, P < 0.001).Conclusion: For NSCLC patients with margin positive disease after surgery, increasing distance was associated with decreased likelihood of receiving PORT, despite being routinely recommended in this setting and proven survival benefit irrespective of geography in our patient cohort. Decreased likelihood to receive PORT with increasing travel distance suggests location may play a role in the decision to undergo PORT for these patients with adverse pathology. [ABSTRACT FROM AUTHOR]

Left atrium longitudinal strain (LAS) with speckle tracking method has been proposed as a non-invasive method for the assessment of left ventricular filling pressure and diastolic dysfunction. This study aimed to investigate left atrial strain compared to invasively measured left ventricular filling pressure. All Patients candidates for coronary angiography were consecutively recruited. LAS measured by transthoracic echocardiography. Left ventricular end-diastolic pressure (LVEDP) pressure was invasively measured. Current echocardiographic modalities for diastolic function evaluated. A total of 125 people were included. 45 patients had preserved ejection fraction (EF ≥ 50%) and 85 patients had reduced EF (EF < 50%) and compared two groups. LVEDP was significantly higher in reduced EF compared to preserved EF (p-value < 0.001). LA-reservoir and LA-booster strains were significantly lower in patients with reduced EF compared to preserved EF (p-value = 0.008, mean Reservoir = 16.4% ± 6.4, mean Reservoir = 19.5% ± 5.6, respectively) and (p-value = 0.009, mean Booster = 9.09% ± 4.0, mean Booster =11. 9% ± 4.3, respectively). LA 4ch-reservoir strain <14.4%, and LA 2ch-reservoir strain <14.1% were related to LVEDP≥20 mmHg (sensitivity 63.5% and specificity 75%) (sensitivity 77.9% and specificity of 60%) respectively. LAS is significantly lower in patients with elevated LVEDP (≥ 20mmHg). LAS is significantly lower in patients with reduced EF. Both LA-reservoir and LA-booster strains have a significant relation to predicting LVFP but LA-reservoir strain is more accurate. The mean LA-reservoir strain less than 12.4% is associated with LVEDP ≥ 20mmHg., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Macrophage-based cell therapies have shown modest success in clinical trials, which can be attributed to their phenotypic plasticity, where transplanted macrophages get reprogrammed towards a pro-tumor phenotype. In most tumor types, including melanoma, the balance between antitumor M1-like and tumor-promoting M2-like macrophages is critical in defining the local immune response with a higher M1/M2 ratio favoring antitumor immunity. Therefore, designing novel strategies to increase the M1/M2 ratio in the TME has high clinical significance and benefits macrophage-based cell therapies., Methods: In this study, we reprogrammed antitumor and proinflammatory macrophages ex-vivo with HDAC6 inhibitors (HDAC6i). We administered the reprogrammed macrophages intratumorally as an adoptive cell therapy (ACT) in the syngeneic SM1 murine melanoma model and patient-derived xenograft bearing NSG-SGM3 humanized mouse models. We phenotyped the tumor-infiltrated immune cells by flow cytometry and histological analysis of tumor sections for macrophage markers. We performed bulk RNA-seq profiling of murine bone marrow-derived macrophages treated with vehicle or HDAC6i and single-cell RNA-seq profiling of SM1 tumor-infiltrated immune cells to determine the effect of intratumor macrophage ACT on the tumor microenvironment (TME). We further analyzed the single-cell data to identify key cell-cell interactions and trajectory analysis to determine the fate of tumor-associated macrophages post-ACT., Results: Macrophage ACT resulted in diminished tumor growth in both mouse models. We also demonstrated that HDAC6 inhibition in macrophages suppressed the polarization toward tumor-promoting phenotype by attenuating STAT3-mediated M2 reprogramming. Two weeks post-transplantation, ACT macrophages were viable, and inhibition of HDAC6 rendered intratumor transplanted M1 macrophages resistant to repolarization towards protumor M2 phenotype in-vivo. Further characterization of tumors by flow cytometry, single-cell transcriptomics, and single-cell secretome analyses revealed a significant enrichment of antitumor M1-like macrophages, resulting in increased M1/M2 ratio and infiltration of CD8 effector T-cells. Computational analysis of single-cell RNA-seq data for cell-cell interactions and trajectory analyses indicated activation of monocytes and T-cells in the TME., Conclusions: In summary, for the first time, we demonstrated the potential of reprogramming macrophages ex-vivo with HDAC6 inhibitors as a viable macrophage cell therapy to treat solid tumors., (© 2024. The Author(s).)

Introduction: Arteriovenous malformations (AVMs) can be treated with observation, surgery, embolization, stereotactic radiosurgery (SRS), or a combination of therapies. SRS has been used for AVMs that pose a high risk of surgery, such as in deep or eloquent anatomic locations. Smaller AVMs, <3 cm, have been shown to have higher rates of complete obliteration after SRS. For AVMs that are a larger size, embolization prior to SRS has been used to reduce the size of the AVM nidus. In this study we analyzed embolization prior to SRS to reduce nidal volume and describe imaging techniques to target for SRS post embolization., Methods: We retrospectively reviewed all patients at a single academic institution treated with embolization prior to SRS for treatment of AVMs. We then used contrast enhanced magnetic resonance imaging (MRI) to contour AVM volumes based on pre-embolization imaging and compared to post-embolization imaging. Planned AVM volume prior to embolization was then compared to actual treated AVM volume., Results: We identified 11 patients treated with embolization prior to SRS from 2011-2023. Median AVM nidal volume prior to embolization was 7.69 mL and post embolization was 3.61 ML (P < 0.01). There was a 45.5% obliteration rate at follow up in our series, with 2 minor complications related to radiosurgery., Conclusions: In our cohort, embolization prior to SRS resulted in a statistically significant reduction in AVM nidal volume. Therefore, embolization prior to SRS can result in dose reduction at time of SRS treatment allowing for decreased risk of SRS complications without higher embolization complication rates., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for prostate cancer. SBRT requires high accuracy to reduce treatment margins. Metal hip prostheses create artifacts that distort pelvic imaging and potentially decrease the accuracy of target/organ at risk (OAR) identification and radiation dose calculations. Data on the safety and efficacy of SBRT after hip replacement is limited. This single-institution study sought to evaluate the safety and local control following SBRT for prostate cancer in men with hip replacements., Methods: 23 patients treated with localized prostate cancer and a history of pre-treatment hip replacement, treated with SBRT from 2007 to 2017 at MedStar Georgetown University Hospital were included in this retrospective analysis. Treatment was administered with the CyberKnife ® (Accuray Incorporated, Sunnyvale, CA) at doses of 35 Gy or 36.25 Gy in 5 fractions. The targets and OARs were identified and contoured by a single experienced Radiation Oncologist (SPC). The adequacy of the CT and T2W MRI images for treatment planning was assessed with a three-point scale (good, adequate, or suboptimal). During treatment planning, care was taken to avoid treatment beams that directly traversed the hip prosthesis. Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Local recurrence was confirmed by magnetic resonance imaging and/or prostate biopsy., Results: The median follow-up was seven years. The patients were elderly (median age = 71 years) with a high rate of comorbidities (Charlson Comorbidity Index > 2 in 25%). Four patients had bilateral hip replacements. The majority of patients were low to intermediate risk per the D'Amico classification. Around 13% received upfront ADT. In total, 13 patients were treated with 35 Gy, and 10 were treated with 36.25 Gy. The rates of late > Grade 3 GU toxicity and > Grade 2 GI toxicity were 8.6% and 4.3%, respectively. There were no Grade 4 or 5 toxicities. Six patients (26%) developed a local recurrence at a median time of 7.5 years. Of these six patients, four had unilateral hip replacements and two had bilateral. Three underwent salvage cryotherapy and three received salvage ADT., Conclusions:  In the general population, high-grade toxicities and local recurrences are uncommon following prostate SBRT. However, in this cohort of patients with prior hip replacements, prostate SBRT had higher than expected rates of late toxicity and local recurrence. In the opinion of the authors, such patients should be counseled regarding an elevated risk of late toxicity and local recurrence with prostate SBRT. With its ultrasound guidance, brachytherapy would have the advantage of circumventing the need for MRI/CT-based imaging and thus may represent a preferable radiation alternative in this patient population. If these patients are treated with SBRT, they should be monitored closely for local recurrence so early salvage can be performed. We hope that recent advances in metal artifact reduction techniques and dose-calculation algorithms will improve future outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Georgetown University Institutional Review Board issued approval 2009-510. Approval from the MedStar Georgetown University Institutional Review Board was obtained for retrospective review of prospectively collected data in our institutional database (IRB#: 2009-510). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This work was supported by the James and Theodore Pedas Family Foundation. Additionally, SP Collins serves as a clinical consultant to Accuray Inc. The Department of Radiation Medicine at Medstar Georgetown University Hospital recieves a grant from Accuray to support a research coordinator. The other authors declare they have no competing interests. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shah et al.)

Background: Although active surveillance is the preferred management for low-risk prostate cancer (PCa), some men remain at risk of overtreatment with definitive local therapy. We hypothesized that baseline characteristics may be associated with overtreatment and represent a potential source of health disparities. We therefore examined the associations of patient and disease characteristics with the surgical overtreatment of low-risk PCa., Methods: We identified men aged 45-75 years with cT1 cN0 cM0 prostate adenocarcinoma with biopsy Gleason score 6 and PSA < 10 ng/ml from 2010-2016 in the National Cancer Database (NCDB) and who underwent radical prostatectomy (RP). We evaluated the associations of baseline characteristics with clinically insignificant PCa (iPCa) at RP (i.e., "overtreatment"), defined as organ-confined (i.e., pT2) Gleason 3 + 3 disease, using multivariable logistic regression., Results: We identified 36,088 men with low-risk PCa who underwent RP. The unadjusted rate of iPCa decreased during the study period, from 54.7% in 2010 to 40.0% in 2016. In multivariable analyses adjusting for baseline characteristics, older age (OR 0.98, 95% CI 0.97-0.98), later year of diagnosis (OR 0.62, 95% CI 0.57-0.67 for 2016 vs. 2010), Black race (OR 0.85, 95% CI 0.79-0.91), treatment at an academic/research program (OR 0.82, 95% CI 0.73-0.91), higher PSA (OR 0.91, 95% CI 0.90-0.92), and higher number of positive biopsy cores (OR 0.87, 95% CI 0.86-0.88) were independently associated with a lower risk of overtreatment (iPCa) at RP. Conversely, a greater number of biopsy cores sampled (OR 1.01, 95% CI 1.01-1.02) was independently associated with an increased risk of overtreatment (iPCa) at RP., Conclusions: We observed an ~27% reduction in rates of overtreatment of men with low-risk PCa over the study period. Several patient, disease, and structural characteristics are associated with detection of iPCa at RP and can inform the management of men with low-risk PCa to reduce potential overtreatment., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Androgen deprivation therapy (ADT) improves local cancer control in unfavorable localized prostate cancer treated with radiotherapy. ADT is known to cause hormonally related symptoms that resolve with testosterone recovery. Hot flashes are particularly burdensome. This study sought to evaluate the timeline of hot flashes following short-course ADT and stereotactic body radiotherapy (SBRT) as well as its relationship with testosterone recovery., Methods: Institutional IRB approval was obtained for this retrospective review of prospectively collected data (IRB#: 2009-510). ADT was initiated three months prior to the start of SBRT. Hot flashes were self-reported via question 13a of the Expanded Prostate Index Composite (EPIC)-26 prior to ADT initiation, the first day of robotic SBRT, and at each follow-up (one, three, six, nine, 12, 18, 24, and 36 months). The responses were grouped into three relevant categories (no problem, very small-small problem, and moderate-big problem). Scores were transformed to a 0-100 scale with higher scores reflecting less bother. Testosterone levels were measured at each follow-up., Results: From 2007 to 2010, 122 localized prostate cancer patients (nine low-, 64 intermediate-, and 49 high-risk according to the D'Amico classification) at a median age of 72 years (range 54.5-88.3) were treated with short course ADT (three to six months) and SBRT (35-36.25 Gy) at Georgetown University Hospital. Thirty-two percent were Black and 27% were obese. Seventy-seven percent of patients received three months of ADT. At baseline, 2% of men experienced hot flashes that were a "moderate to big problem" and that proportion peaked at the start of SBRT (45%) before returning to baseline (2%) nine months post-SBRT with a cumulative incidence of 52.4%. The median baseline EPIC-26 hot flash score of 94 declined to 50 at the start of SBRT but this returned to baseline (92) by six months post SBRT. These changes were both statistically and clinically significant (MID = 9.5083, p<0.01). Testosterone recovery (> 230 ng/dL) occurred in approximately 70% of patients by 12 months post SBRT. Resolution of hot flashes correlated with testosterone recovery., Conclusion: Bothersome hot flashes occur in greater than 50% of men treated with neoadjuvant ADT. Resolution of hot flashes occurs in the majority of patients within one year after treatment. Reassurance of the temporary nature of hot flashes may assist in reducing patient anxiety. Measuring testosterone levels at follow-up visits may allow for anticipatory counseling that may limit the associated bother., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Shah et al.)

Objective: Hypertensive disorders during pregnancy are a significant cause of maternal and perinatal mortality and morbidity worldwide. White coat hypertension (WCH) is a hypertensive disease characterized by an increased clinic blood pressure but normal home or workplace blood pressure. Due to variable prevalence, a subset of women with WCH may be incorrectly diagnosed with chronic hypertension, highlighting the need for accurate diagnosis. Little is known about the role of WCH in pregnancy, but a meta-analysis aims to determine whether WCH increases the likelihood of developing preeclampsia., Methods: A systematic review and meta-analysis was conducted to determine whether there is an association between WCH and the incidence of preeclampsia in pregnant women. The search included PubMed, Embase, and Scopus databases until February 2023, using PRISMA guidelines. Pregnant women with apparent office hypertension throughout pregnancy who underwent 24-hour ambulatory blood pressure monitoring or home blood pressure monitoring were included. Meta-analysis was performed using RevMan., Results: This study included 12 studies with a total of 4,672 pregnant women and found that women with WCH have a higher risk of developing preeclampsia compared to normotensive women (RR: 2.29, 95% CI [1.18,4.43], P = 0.01). However, when compared with pregnant women with gestational hypertension or chronic hypertension, women with WCH had a significantly lower risk of developing preeclampsia ((RR: 0.39, [0.20,0.80], p=0.009) and (RR: 0.41, [0.27,0.62], P<0.001), respectively)., Conclusion: The study recommends incorporating 24-hour ABPM into clinical practice to differentiate between chronic hypertension and WCH in early pregnancy and focus on special management for those who need it. The findings may guide future research on ABPM's role in diagnosing WCH and its effects on pregnancy outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)