Effect of Colchicine on Progression of Known Coronary Atherosclerosis in Patients with STable CoROnary Artery Disease CoMpared to Placebo (EKSTROM) Trial - Rationale and Design.

BACKGROUND: Cardiovascular disease is the major cause of mortality in the United States. Despite lifestyle modification and traditional risk factor control residual inflammatory risk remains an untreated concern. Colchicine is an oral, medication that has been used for gout, mediterranean fever and pericarditis for decades. In recent trials, colchicine has been shown to reduce major adverse cardiovascular events, however the mechanism of benefit remains unclear. The objective of the randomized, double-blind, placebo controlled EKSTROM trial is to evaluate the effects of colchicine 0.5mg/day on atherosclerotic plaque. METHODS: Eighty-four participants will be enrolled after obtaining informed consent and followed for 12 months. Eligible patients will be randomly assigned to colchicine 0.5mg/day or placebo in a 1:1 fashion as add-on to their standard of care. All participants will undergo coronary computed tomography angiography (CCTA) at baseline and at 12 months. RESULTS: As of November 2023, the study is 100% enrolled with an expected end of study by the second quarter of 2024. The primary endpoint is change in low attenuation plaque volume as measured by CCTA. Secondary endpoints include change in volume of different plaque types (including total atheroma volume, noncalcified plaque volume, dense calcified plaque volume, remodeling index), change in inflammatory markers (IL-6, IL-1ß, IL-18, hs-CRP), change in pericoronary adipose tissue attenuation, change in epicardial adipose tissue volume and attenuation and change in brachial flow mediated dilation. CONCLUSION: EKSTROM is the first randomized study to assess the effects of colchicine on plaque progression, pericoronary and epicardial fat. EKSTROM will provide important information on the mechanistic effects of colchicine on the cardiovascular system.

The prognostic impact of substantial lymphovascular space invasion in women with node negative FIGO stage I uterine carcinoma.

OBJECTIVE: Substantial lymphovascular space invasion (LVSI) is an important predictor of lymph node (LN) involvement in women with endometrial carcinoma. We studied the prognostic significance of substantial LVSI in patients with 2009-FIGO stage-I uterine endometrioid adenocarcinoma (EC) who all had pathologic negative nodal evaluation (PNNE). METHODS: Pathologic specimens were retrieved and LVSI was quantified (focal or substantial) in women with stage-I EC who had a hysterectomy and PNNE. In addition to multivariate analysis (MVA), recurrence-free (RFS), disease-specific (DSS), and overall (OS) survival was compared between women with focal vs. substantial LVSI. RESULTS: 1052 patients were identified with a median follow-up of 9.7 years. 358 women (34%) received adjuvant radiotherapy. 907 patients (86.2%) had no LVSI, 87 (8.3%) had focal, and 58 (5.5%) had substantial LVSI. Five-year RFS was 93.3% (95% CI: 91.5-95.1), 76.8% (95% CI: 67.2-87.7) and 79.1% (95% CI: 67.6-95.3) for no, focal, and substantial LVSI(p < 0.0001). There was no statistically significant difference in 5-year RFS, DSS, OS, and in the patterns of initial recurrence between women with focal vs substantial LVSI. On MVA with propensity score matching, substantial LVSI was not independently associated with any survival endpoint compared to focal LVSI, albeit both were detrimental when compared to no LVSI. Age ≥ 60 years and higher grade were predictors of worse RFS, DSS, and OS. Additionally, comorbidity burden was an independent predictor for OS. CONCLUSIONS: Our results suggest that substantial LVSI does not predict worse survival endpoints or different recurrence patterns in women with stage-I EC with PNNE when compared to focal LVSI.

Defibrillation strategies for refractory ventricular fibrillation out-of-hospital cardiac arrest: A systematic review and network meta-analysis.

BACKGROUND AND OBJECTIVE: Double sequential external defibrillation (DSED) and vector-change defibrillation (VCD) have been suggested to enhance clinical outcomes for patients with ventricular fibrillation (VF) refractory of standard defibrillation (SD). Therefore, this network meta-analysis aims to evaluate the comparative efficacy of DSED, VCD, and SD for refractory VF. METHODS: A systematic review and network meta-analysis synthesizing randomized controlled trials (RCTs) and comparative observational studies retrieved from PubMed, EMBASE, WOS, SCOPUS, and Cochrane through November 15th, 2022. R software netmeta and netrank package (R version 4.2.0) and meta-insight software were used to pool dichotomous outcomes using odds ratio (OR) presented with the corresponding confidence interval (CI). Our protocol was prospectively published in PROSPERO with ID: CRD42022378533. RESULTS: We included seven studies with a total of 1632 participants. DSED was similar to SD in survival to hospital discharge (OR: 1.14 with 95% CI [0.55, 2.83]), favorable neurological outcome (modified Rankin scale ≤2 or cerebral performance category ≤2) (OR: 1.35 with 95% CI [0.46, 3.99]), and return of spontaneous circulation (ROSC) (OR: 0.81 with 95% CI [0.43; 1.5]). In addition, VCD was similar to SD in survival to hospital discharge (OR: 1.12 with 95% CI [0.27, 4.57]), favorable neurological outcome (OR: 1.01 with 95% CI [0.18, 5.75]), and ROSC (OR: 0.88 with 95% CI [0.24; 3.15]). CONCLUSION: Double sequential external defibrillation and VCD were not associated with enhanced outcomes in patients with refractory VF out-of-hospital cardiac arrest, compared to SD. However, the current evidence is still inconclusive, warranting further large-scale RCTs.

Cetuximab and anemia prevention in head and neck cancer patients undergoing radiotherapy.

BACKGROUND: Epidermal growth factor receptor (EGFR) activation is associated with increased production of interleukin 6 (IL6), which is intensified by radiotherapy (RT) induced inflammatory response. Elevated IL6 levels intensifies RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, has been associated with lower rates of anemia for locally advanced head and neck squamous cell carcinoma (HNSCC). We hypothesized that concomitant cetuximab could prevent RT-induced anemia. METHODS: We queried our institutional head and neck cancers database for non-metastatic HNSCC cases that received RT with concomitant cetuximab or RT-only between 2006 and 2018. Cetuximab was administered for some high-risk cases medically unfit for platinum agents per multidisciplinary team evaluation. We only included patients who had at least one complete blood count in the 4 months preceding and after RT. We compared the prevalence of anemia (defined as hemoglobin (Hb) below 12 g/dL in females and 13 g/dL in males) and mean Hb levels at baseline and after RT. Improvement of anemia/Hb (resolution of baseline anemia and/or an increase of baseline Hb ≥1 g/dL after RT), and overall survival (OS) in relation to anemia/Hb dynamics were also compared. RESULTS: A total of 171 patients were identified equally distributed between cetuximab-plus-RT and RT-only groups. The cetuximab-plus-RT group had more locally-advanced stage, oropharyngeal and high grade tumors (p < 0.001 for all). Baseline anemia/Hb were similar, however anemia after RT conclusion was higher in the cetuximab-plus-RT vs RT-only (63.5% vs. 44.2%; p = 0.017), with a mean Hb of 11.98 g/dL vs. 12.9 g/dL; p = 0.003, for both respectively. This contributed to significantly worse anemia/Hb improvement for cetuximab-plus-RT (18.8% vs. 37.2%; p = 0.007). This effect was maintained after adjusting for other factors in multivariate analysis. The prevalence of iron, vitamin-B12 and folate deficiencies; and chronic kidney disease, was non-different. Baseline anemia was associated with worse OS (p = 0.0052) for the whole study cohort. Nevertheless, improvement of anemia/Hb was only marginally associated with better OS (p = 0.068). CONCLUSIONS: In contrast to previous studies, cetuximab was not associated with lower rates of anemia after RT for nonmetastatic HNSCC patients compared to RT-alone. Dedicated prospective studies are needed to elucidate the effect of cetuximab on RT-induced anemia.

Bariatric surgery during COVID-19 in the UK: a British Obesity and Metabolic Surgery Society (BOMSS) survey.

BACKGROUND: After the declaration of COVID-19 as a pandemic last March 2020, several adjustments in surgical services were implemented. Plans are now being formulated for restarting bariatric surgery. The aim of this survey is to capture the practice during the pandemic and the readiness to restart to provide a framework to deal with the backlog of bariatric cases. METHOD: A survey was delivered to consultant surgeon members of the British Obesity and Metabolic Surgery Society and non-bariatric surgery consultant members of the Association of Upper GI Surgeons. RESULTS: The survey elicited a response rate of 40% (n = 66) among bariatric surgeons and 15.5% (n = 34) between non-bariatric surgeons. The average question response rate was 93% (88-100%). Most of the elective bariatric surgeries and clinics were cancelled early after declaration of the pandemic. Remote technologies for patient education evolved and were used heavily during the pandemic. The average cancelled elective bariatric surgery operations per week was 9. Nearly a quarter of responders reported performing emergency bariatric surgery during the pandemic. Most of the bariatric surgeons reported being ready to restart the service within 1-2 months. Responders recommended using private sector beds to increase NHS capacity and using the link between obesity and poor COVID-19 outcomes to push for prioritisation of bariatric patients. CONCLUSION: This survey is an attempt to understand the impact of COVID-19 on UK bariatric service and the preparedness to restart. It expressed the bariatric surgery consultants' view of prioritisation of bariatric patients on clinical basis rather than the first-come-first-served basis.

Photoluminescent and photochromic smart window from recycled polyester reinforced with cellulose nanocrystals.

Smart windows with long-persistent phosphorescence, ultraviolet (UV) light protection, high transparency, and high rigidity were developed by easily immobilizing varying ratios of lanthanide-activated aluminate phosphor nanoscale particles within a composite of recycled polyester/cellulose nanocrystals (RPET/CNC). Cellulose nanocrystals were prepared from rice straw waste. Cellulose nanocrystals were used at low concentration as both crosslinker and drier to improve both transparency and hardness. The phosphor nanoscale particles must be distributed into the recycled polyester/cellulose nanocrystals composite bulk without agglomeration to produce transparent RPET/CNC substrates. Photoluminescence characteristics were also studied using spectroscopic profiles of excitation/emission and decay/lifetime. The hardness efficiency was also examined. This transparent recycled polyester waste/cellulose nanocrystals nanocomposite smart window has been shown to change colour under UV light to strong green and to greenish-yellow when it is dark, as proved by Commission Internationale de l'éclairage (CIE) laboratory colour parameters. It was found that the afterglow RPET/CNC smart window had phosphorescence intensities of 428, 493, and 523 nm upon excitation at 368 nm. There was evidence of improved UV shielding, photostability, and hydrophobic activity. In the presence of a low phosphor ratio, the luminescent RPET/CNC substrates showed quick and reversible fluorescence photochromic activity when exposed to UV radiation.

Magnetic resonance imaging of severe idiopathic club foot treated with one-week accelerated Ponseti (OWAP) technique.

PURPOSE: This study aims to evaluate changes in tarsal bones relationship after the use of one week accelerated Ponseti method in the treatment of severe idiopathic clubfoot using MRI. We hypothesize that one-week accelerated Ponseti is at least as effective as standard techniques in achieving the desirable MRI parameters. METHODS: This is a prospective study of 8 children with severe idiopathic clubfeet (Pirani 6) (4 unilateral and 4 bilateral) treated before the age of three months with one-week accelerated Ponseti technique, as described in a former study with minimum 2-year follow-up. The 8 corrected feet were compared with the 4 unilateral normal feet at clinical and radiological levels using a Pirani scoring system and an MRI, respectively. RESULTS: Clinical results showed that Pirani score was 1.1 in the last follow up in comparison to Pirani 6 pretreatment (p < 0.05). MRI results indicated that the malleocalcaneal angle, axial malleocalcaneal index, coronal tibiocalcaneal angle, sagittal talocalcaneal angle, and talar head neck calcaneal rotation showed statistical difference between the two groups (p < 0.05). Sagittal malleocalcaneal index, sagittal tibiocalcaneal angle, talar head neck rotation related to talar body, and posterior calcaneal rotation showed no statistical difference between normal feet and clubfeet after correction (p value >0.05). CONCLUSION: One-week accelerated Ponseti technique showed to be as effective and safe as other treatment methods through clinical and MRI follow up data. MRI role was to confirm the efficiency of this innovative accelerated technique, but not used as a routine follow up.

COVID-19 IgG/IgM antibody testing in Los Angeles County, California.

Evidence suggests that asymptomatic and mild SARS-CoV-2 infections comprise > 95% of all cases. Developing a test that indicates past infection and possible immunity against the virus is important. We administered 244 antibody tests to three groups of high-risk population. The test consisted of an IgG component and an IgM component. The overall IgM/IgG positivity for patients with none, mild, moderate, and severe symptoms were 21.1%, 21.8%, 14.2%, and 26.9%, respectively. Those with moderate or severe symptoms were no more or less likely to have positive antibody tests than those with no or mild symptoms.

Charlson Comorbidity score influence on prostate cancer survival and radiation-related toxicity.

INTRODUCTION: In addition to survival endpoints, we explored the impact of Charlson Comorbidity-Index (CCI) on the acute and late toxicities in men with localized prostate cancer who received dose-escalated definitive radiotherapy (RT). MATERIALS AND METHODS: CCI scores at diagnosis and survival outcomes were identified for men with intermediate/high-risk prostate cancer treated with RT (1/2007-12/2012). Study-cohort was accordingly grouped into no, mild and severe comorbidity (CCI-0, 1 or 2+). CCI-groups were compared for demographics, prognostic-factors; and RT-related toxicities based on RTOG/CTCAE criteria. Kaplan-Meier curves and Uni/multivariate (MVA) analyses were used to examine the influence of CCI-group on overall (OS), disease-specific (DSS) and biochemical-relapse free (BRFS) survival. RESULTS: We included 257 patients with median age 73 years (48-85), 53% African-American and 67% had intermediate-risk. Median prostate RT-dose was 76 Gy; and 47% received androgen-deprivation therapy. CCI-0,1,2+ groups encompassed 76 (30%), 54 (21%) and 127 (49%) patients, respectively and were well-balanced. Ten and 15-years OS were significantly different (76% versus 46% versus 55% for 10-years OS and 53% versus 31% versus 14% for 15-years OS for CCI-0 versus CCI-1[HR:2.25; CI[1.31-3.87]] versus CCI-2+[HR:2.73; CI[1.73-4.31]]; p < 0.001. CCI-0 had better DSS than CCI-2+ (HR:2.23; CI[1.06-4.68]; p = 0.03) and BRFS was similar (p = 0.99). Late G2/3 RT-toxicities were more common in CCI-2+ (47%) than CCI-1 (44%) and CCI-0 (29%), p = 0.032; with non-different acute-toxicities (p = 0.62). On MVA, increased CCI was deterministic for OS (HR:3.65; CI [1.71:7.79]; p < 0.001) and was only marginal for DSS (HR:2.55; CI [0.98-6.6]; p = 0.05) with no impact on BRFS (p > 0.05). CONCLUSIONS: Higher CCI is a significant predictor for late RT-related side-effects and shorter OS in men with localized prostate cancer. Baseline comorbidities should be considered during initial counseling and follow up visits.

The predictive value of the platelet volume parameters in evaluation of varicocelectomy outcome in infertile patients.

The aim of this study was to evaluate the role of platelet count (PLT) and platelet volume indices (PVI) such as mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) as a clinical biomarker in 64 infertile males with varicocele and 45 controls. In addition, semen parameters, serum total testosterone, FSH and testicular volume were measured before and at 6 months after varicocelectomy. The mean PLT, MPV, PDW and PCT were 231 ± 42 × 103/µl, 9.6 ± 1.8 fl, 16.2 ± 2.5 fl and 0.18% in the patient group respectively. When the patient and control groups were compared, there was a significant increase in mean MPV, PDW and PCT (p < .0001), while platelet count was lower in patients than control group, but with no significant relationship. MPV had a significant negative correlation with total testosterone (p < .03). No significant correlations were found between PVI and testicular volume. After follow-up of 37.1 ± 1.9 months, a significant negative correlation was found between the preoperative MPV and varicocelectomy outcome in terms of semen values (p < .007). So, the increase in MPV and low total testosterone in men with varicocele may be a feature of high risk of infertility.

Incorporating sensitive cardiac substructure sparing into radiation therapy planning.

PURPOSE: Rising evidence suggests that cardiac substructures are highly radiosensitive. However, they are not routinely considered in treatment planning as they are not readily visualized on treatment planning CTs (TPCTs). This work integrated the soft tissue contrast provided by low-field MRIs acquired on an MR-linac via image registration to further enable cardiac substructure sparing on TPCTs. METHODS: Sixteen upper thoracic patients treated at various breathing states (7 end-exhalation, 7 end-inhalation, 2 free-breathing) on a 0.35T MR-linac were retrospectively evaluated. A hybrid MR/CT atlas and a deep learning three-dimensional (3D) U-Net propagated 13 substructures to TPCTs. Radiation oncologists revised contours using registered MRIs. Clinical treatment plans were re-optimized and evaluated for beam arrangement modifications to reduce substructure doses. Dosimetric assessment included mean and maximum (0.03cc) dose, left ventricular volume receiving 5Gy (LV-V5), and other clinical endpoints. As metrics of plan complexity, total MU and treatment time were evaluated between approaches. RESULTS: Cardiac sparing plans reduced the mean heart dose (mean reduction 0.7 ± 0.6, range 0.1 to 2.5 Gy). Re-optimized plans reduced left anterior descending artery (LADA) mean and LADA0.03cc (0.0-63.9% and 0.0 to 17.3 Gy, respectively). LV0.03cc was reduced by >1.5 Gy for 10 patients while 6 cases had large reductions (>7%) in LV-V5. Left atrial mean dose was equivalent/reduced in all sparing plans (mean reduction 0.9 ± 1.2 Gy). The left main coronary artery was better spared in all cases for mean dose and D0.03cc . One patient exhibited >10 Gy reduction in D0.03cc to four substructures. There was no statistical difference in treatment time and MU, or clinical endpoints to the planning target volume, lung, esophagus, or spinal cord after re-optimization. Four patients benefited from new beam arrangements, leading to further dose reductions. CONCLUSIONS: By introducing 0.35T MRIs acquired on an MR-linac to verify cardiac substructure segmentations for CT-based treatment planning, an opportunity was presented for more effective sparing with limited increase in plan complexity. Validation in a larger cohort with appropriate margins offers potential to reduce radiation-related cardiotoxicities.

Catalytic domain of deubiquitinylase USP48 directs interaction with Rel homology domain of nuclear factor kappaB transcription factor RelA.

The activity and close regulation of nuclear factor kappaB (NF-κB) transcription factors is critical for a variety of cellular processes including inflammation, immunity, differentiation and cell survival. Thus, dysregulation of the NF-κB system could lead to serious diseases, e.g. uncoordinated growth of the normal tissue during the development of cancer. Transcriptional activity of the NF-κB factor RelA is regulated by a number of mechanisms which comprise ubiquitinylation by a multimeric ubiquitin ligase containing Elongins B and C, cullin-2 (Cul2) and suppressor of cytokine signaling 1 (SOCS1), but also USP48-dependent deubiquitinylation. Further, USP48 promotes cell survival and antagonizes also other E3 ligase functions which are involved in genome stability and DNA repair. The regulation of RelA by USP48 has been investigated in detail, but the domains of USP48 and RelA for direct interaction are not known. In this study we report that USP48 interacts physically with RelA in the nucleus. Further, we show by overexpression of truncated proteins that the catalytic USP domain of USP48 interacts with the N-terminal region of the Rel homology domain (RHD) of RelA. This study provides first evidence that the USP domain of USP48 is important for the physical association with substrate proteins, and a suitable target for small molecule inhibitors for therapeutic intervention strategies.

Assessment of the Correlation Between Preoperative and Immediate Postoperative Gastric Volume and Weight Loss After Sleeve Gastrectomy Using Computed Tomography Volumetry.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has achieved excellent results in treatment of morbid obesity. The present study aimed to evaluate the impact of the preoperative gastric volume, volume of the remaining gastric pouch, and volume of the resected stomach on weight loss after LSG. METHODS: Patients with morbid obesity who underwent LSG were investigated by CT volumetry before and 1 week after LSG to measure the volume of the stomach before and after the procedure, and the volume of the resected stomach was also calculated. The percentage of excess weight loss (EWL) and decrease in body mass index (BMI) at 6 months postoperatively were measured and correlated with preoperative and postoperative gastric volumes. RESULTS: Forty-seven patients (44 females) were included to the study. A significant decrease in the gastric volume and BMI after LSG was noted. Preoperative gastric volume was positively correlated with preoperative BMI (r = 0.723, p < 0.00001) but not correlated with %EWL at 6 months. The volume of the remaining gastric pouch was positively correlated with BMI at 6 months postoperatively (r = 0.597, p < 0.00001) and negatively correlated with %EWL (r = -0.7495, p < 0.00001). The correlation between the size of resected stomach and %EWL was statistically insignificant, yet the mean percentage of the resected stomach was directly correlated to %EWL. CONCLUSION: The preoperative volume of the stomach was positively correlated with baseline BMI, but not correlated with %EWL. The size of the remaining gastric pouch and the percentage of the resected stomach had significant impact on %EWL after LSG.

Impact of CT reconstruction algorithm on auto-segmentation performance.

Model-based iterative reconstruction (MBIR) reduces CT imaging dose while maintaining image quality. However, MBIR reduces noise while preserving edges which may impact intensity-based tasks such as auto-segmentation. This work evaluates the sensitivity of an auto-contouring prostate atlas across multiple MBIR reconstruction protocols and benchmarks the results against filtered back projection (FBP). Images were created from raw projection data for 11 prostate cancer cases using FBP and nine different MBIR reconstructions (3 protocols/3 noise reduction levels) yielding 10 reconstructions/patient. Five bony structures, bladder, rectum, prostate, and seminal vesicles (SVs) were segmented using an auto-segmentation pipeline that renders 3D binary masks for analysis. Performance was evaluated for volume percent difference (VPD) and Dice similarity coefficient (DSC), using FBP as the gold standard. Nonparametric Friedman tests plus post hoc all pairwise comparisons were employed to test for significant differences (P < 0.05) for soft tissue organs and protocol/level combinations. A physician performed qualitative grading of 396 MBIR contours across the prostate, bladder, SVs, and rectum in comparison to FBP using a six-point scale. MBIR contours agreed with FBP for bony anatomy (DSC ≥ 0.98), bladder (DSC ≥ 0.94, VPD < 8.5%), and prostate (DSC = 0.94 ± 0.03, VPD = 4.50 ± 4.77% (range: 0.07-26.39%). Increased variability was observed for rectum (VPD = 7.50 ± 7.56% and DSC = 0.90 ± 0.08) and SVs (VPD and DSC of 8.23 ± 9.86% range (0.00-35.80%) and 0.87 ± 0.11, respectively). Over the all protocol/level comparisons, a significant difference was observed for the prostate VPD between BSPL1 and BSTL2 (adjusted P-value = 0.039). Nevertheless, 300 of 396 (75.8%) of the four soft tissue structures using MBIR were graded as equivalent or better than FBP, suggesting that MBIR offered potential improvements in auto-segmentation performance when compared to FBP. Future work may involve tuning organ-specific MBIR parameters to further improve auto-segmentation performance. Running title: Impact of CT Reconstruction Algorithm on Auto-segmentation Performance.

Coronary calcification in adults with Turner syndrome.

PurposeAdults with Turner syndrome (TS) have an increased predisposition to ischemic heart disease. The quantitative relationship between coronary atherosclerosis and TS has yet to be established.MethodsA total of 128 females (62 with TS) participated in this prospective study. Coronary computed tomography angiography was performed to measure coronary calcified plaque burden, and prevalent noncalcified plaque burden. Regression analysis was used to study the effects of TS and traditional cardiovascular disease risk factors on coronary plaque burden.ResultsAdults with TS were 63% more likely to have coronary calcifications than controls (odds ratio 1.63, 95% confidence interval: 1.02, 2.61, P = 0.04), with an age cutoff of 51.7 years for a probability of >50% for the presence of coronary calcifications, when compared to 55.7 years in female controls. The average age of TS patients with calcified plaques was significantly lower than that of controls with calcified plaques (51.5 ± 8.9 years vs. 60.5 ± 7.0 years, P < 0.001). Age increased the likelihood of coronary calcifications by 13% per year (odds ratio 1.13, confidence interval 95%: 1.07-1.19, P < 0.001).ConclusionThis study demonstrates a higher prevalence and earlier onset of calcified coronary plaques in TS. These findings have important implications for cardiovascular risk assessment and the management of patients with TS.

Rheological determinants for simultaneous staging of hepatic fibrosis and inflammation in patients with chronic liver disease.

The purpose of this study is to investigate the use of fundamental rheological parameters as quantified by MR elastography (MRE) to measure liver fibrosis and inflammation simultaneously in humans. MRE was performed on 45 patients at 3 T using a vibration frequency of 56 Hz. Fibrosis and inflammation scores were obtained from liver biopsies. Biomechanical properties were quantified in terms of complex shear modulus G* as well as shear wave phase velocity c and shear wave attenuation α. A rheological fractional derivative order model was used to investigate the linear dependence of the free model parameters (dispersion slope y, intrinsic speed c0 , and intrinsic relaxation time τ) on histopathology. Leave-one-out cross-validation was then utilized to demonstrate the effectiveness of the model. The intrinsic speed c0 increases with hepatic fibrosis, while an increased relaxation time τ is reflective of more inflammation of the liver parenchyma. The dispersion slope y does not depend either on fibrosis or on inflammation. The proposed rheological model, given this specific parameterization, establishes the functional dependences of biomechanical parameters on histological fibrosis and inflammation. The leave-one-out cross-validation demonstrates that the model allows identification, from the MRE measurements, of the histology scores when grouped into low-/high-grade fibrosis and low-/high-grade inflammation with significance levels of P = 0.0004 (fibrosis) and P = 0.035 (inflammation). The functional dependences of intrinsic speed and relaxation time on fibrosis and inflammation, respectively, shed new light onto the impact hepatic pathological changes on liver tissue biomechanics in humans. The dispersion slope y appears to represent a structural parameter of liver parenchyma not impacted by the severity of fibrosis/inflammation present in this patient cohort. This specific parametrization of the well-established rheological fractional order model is valuable for the clinical assessment of both fibrosis and inflammation scores, going beyond the capability of the plain shear modulus measurement commonly used for MRE.

What Is the Optimal Adjuvant Treatment Sequence for Node-Positive Endometrial Cancer? Results of a National Cancer Database Analysis.

OBJECTIVE: The optimal sequence of administering chemotherapy (CT) and radiation treatment (RT) in women with node-positive endometrial carcinoma (EC) remains controversial. We used the National Cancer Database to evaluate overall survival (OS) in women with advanced EC receiving different sequences of adjuvant therapy. METHODS: The National Cancer Database was queried for female adults with International Federation of Gynecology and Obstetrics 2009 stage IIIC1 to IIIC2 EC diagnosed from 2004 to 2012 treated with hysterectomy and adjuvant CT and RT. Overall survival was compared between sequential treatment (CT followed by RT) and concurrent treatment (CT and RT within 4 weeks). χ tests assessed differences by sequence and various clinical variables. Log-rank test and Cox proportional hazards models evaluated OS. Risk factors related to OS were identified by univariate and multivariate analyses. RESULTS: Of 1826 patients, 67% (1218) received sequential treatment and 33% (608) received concurrent treatment. The median follow-up was 49.2 months. The sequential treatment group had a better 5-year OS (67% [95% confidence interval = 64%-70%]) than the concurrent treatment group (62% [95% confidence interval = 57%-66%]) (P = 0.004). On multivariate analysis, the strongest predictors of worse OS were increasing age (hazard ratio [HR] = 1.04 [1.02-1.06], P = 0.0003), type 2 versus type 1 EC (HR = 1.60 [1.06-2.43], P = 0.03), grade 3 versus 1 (HR = 2.64 [1.23-5.67], P = 0.01), residual disease or positive margin versus negative margin (HR = 2.25 [1.43-3.56], P = 0.0005), and concurrent versus sequential treatment (HR = 1.67 [1.15-2.40], P = 0.006). CONCLUSIONS: This study suggests that upfront CT followed by RT may be a better treatment sequence for adjuvant therapy in women with advanced EC.

Predictors of myocardial functional recovery following successful reperfusion of acute ST elevation myocardial infarction.

BACKGROUND: Following acute ST elevation myocardial infarction (STEMI), restoration of large-vessel patency does not mean complete perfusion recovery. Little is known regarding the predictors of successful myocardial reperfusion for the STEMI patients undergoing pharmacologic and mechanical reperfusion strategies. AIM OF THE WORK: The aim of this clinical study was to find out the predictors of myocardial functional recovery following reperfusion of acute STEMI, represented by 3-month global longitudinal strain (GLS) value assessed by speckle tracking echocardiography. MATERIAL/METHODS: The study population included 400 patients presented with first acute STEMI with successful reperfusion by thrombolysis (group I) or primary percutaneous coronary intervention (PPCI) (group II). Electrocardiography (ECG) at baseline and 90 minutes after coronary reperfusion was performed with assessment of ST resolution. Basal and 3-month follow-up echocardiography was performed with assessment of ejection fraction (EF), myocardial performance index (MPI), systolic myocardial excursion (S'), and GLS. RESULTS: There was nonsignificant difference between patients of both groups regarding age (P = 0.422) and gender (P = 0.272). Also, there was a nonsignificant difference between both groups regarding the risk factors of coronary artery disease like hypertension (P = 0.511), diabetes mellitus (P = 0.332), and smoking (P = 0.381). But there was significant statistical difference between both groups regarding dyslipidemia (P = 0.012). Ninety-minute ST resolution was significantly higher in PPCI group (P = 0.042). Moreover, PPCI group had significant improvement of EF (P = 0.013) during follow-up, and highly significant improvement of MPI, S' and GLS (P Ë‚ 0.001) compared to the basal echocardiographic study. The percentage of change (∆) of each of the echocardiographic parameter was compared between both groups and revealed statistically significant improvement regarding EF, highly significant improvement of MPI, S' and GLS in favor of PPCI arm (group II). Multivariate regression analysis demonstrated that pain to reperfusion time, MI territory, ST resolution, and basal GLS value are the most important predictors for LV functional recovery. CONCLUSION: The study found pain to reperfusion time, MI territory, ST resolution, basal GLS value are the most important predictors of myocardial functional recovery. Regular follow-up with echocardiography for STEMI patients with different reperfusion strategies has informative impact on long-term clinical outcome. Also the study confirmed that PPCI is better than thrombolysis not only in restoring epicardial coronary flow but also in restoring microvascular and tissue perfusion assuring better myocardial functional recovery and better long-term clinical outcomes.

Does Age-Adjusted Charlson Comorbidity Score Impact Survival Endpoints in Women with Federation of Gynecology and Obstetrics-Stage III Endometrial Cancer?

OBJECTIVES: We sought to evaluate the impact of age-adjusted Charlson comorbidity index (AACCI) score on survival endpoints for women with advanced stage endometrial carcinoma (EC). METHODS AND MATERIALS: We identified 238 women with stage III EC. AACCI score was calculated and 3 groups were created accordingly; group 1 with a score of 0-2, group 2 with score 3-4, and group 3 with score ≥5. Significant predictors of recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were analyzed. RESULTS: Median follow-up was 54 months and median age was 65 years. Stage IIIC was the most common stage (69%). The 3 groups were well-balanced except for less utilization of adjuvant chemotherapy in group 3 (p = 0.01). Five-year OS was significantly lower in group 3 compared to groups 1 and 2 (23 vs. 65 and 51%, respectively). Similarly, 5-year RFS was 54, 41, and 33% and DSS was 65, 54, and 35% for groups 1, 2, and 3 respectively. On multivariate analyses, AACCI group 3, cervical stromal involvement, positive peritoneal cytology, and higher tumor grade were predictors for shorter OS. Cervical stromal involvement and higher grade were independent predictors for worse RFS and DSS. Additionally, positive cytology, lymphovascular space invasion, and stage IIIC2 were significantly detrimental for RFS. CONCLUSIONS: Our study suggests that comorbidity burden is a strong predictor of worse OS in women with stage III EC. Women with higher AACCI are less likely to receive adjuvant chemotherapy. Comorbidity score can significantly impact survival endpoints for women with advanced EC.

Hilfer-Katugampola fractional stochastic differential inclusions with Clarke sub-differential.

The objective of this paper is to investigate the existence of mild solutions and optimal controls for a class of stochastic Hilfer-Katugampola fractional differential inclusions (SHKFDIs) with non-instantaneous impulsive (NIIs) that is strengthened by Brownian motion (BM) and the Clarke sub-differential. First, we establish a new set of sufficient conditions for the existence of mild solutions of the aforementioned fractional systems by using stochastic analysis, the Clarke sub-differential's characteristics, and the multi-valued fixed point theorem. Subsequently, by employing Balder's theorem, the existence of optimal control pairs for the considered system is investigated. Eventually, an example is provided to validate the obtained results.