Search

IntroductionMany studies have reported the importance of the human microbiome in relationship to the overall health of its host. While recent studies have explored the microbiome’s role in various types of cancer compared to healthy patients, this pilot study is the first to investigate differences in the skin microbiome composition among pancreatic adenocarcinoma patients, individuals with other cancers, and cancer-free controls.MethodsThe study characterizes the skin microbiome’s potential associations with cancer status by analyzing skin swabs from the forehead and cheek of 58 participants using Next Generation Sequencing (NGS), differential abundance analysis, and machine learning techniques.ResultsThe study results indicated that the cancer group displayed a significantly higher mean alpha diversity compared to the control group. Additionally, a machine learning classification model achieved a mean F1 Score of 0.943 in predicting cancer status, indicating measurable differentiation in the skin microbiome between the study groups. This differentiation is supported by differential abundance methods, including ANCOM-BC and MaAsLin2.DiscussionThis pilot study suggests that skin microbiome profiling could serve as a non-invasive biomarker for cancer detection and monitoring, which warrants a larger, longitudinal study to validate these results.

Abstract Background A previous phase IB/II study of nab‐paclitaxel + cisplatin + gemcitabine (NABPLAGEM) in 25 patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC) demonstrated favorable results. This phase II study was conducted to further evaluate the safety, efficacy, and impact on quality of life (QOL) of NABPLAGEM in a multi‐center setting. Methods Participants were ≥18 years; had measurable PDAC; Karnofsky performance status of ≥70%; life expectancy ≥12 weeks;

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy in need of new therapeutic options. Using unbiased analyses of super-enhancers (SEs) as sentinels of core genes involved in cell-specific function, here we uncover a druggable SE-mediated RNA-binding protein (RBP) cascade that supports PDAC growth through enhanced mRNA translation. This cascade is driven by a SE associated with the RBP heterogeneous nuclear ribonucleoprotein F, which stabilizes protein arginine methyltransferase 1 (PRMT1) to, in turn, control the translational mediator ubiquitin-associated protein 2-like. All three of these genes and the regulatory SE are essential for PDAC growth and coordinately regulated by the Myc oncogene. In line with this, modulation of the RBP network by PRMT1 inhibition reveals a unique vulnerability in Myc-high PDAC patient organoids and markedly reduces tumor growth in male mice. Our study highlights a functional link between epigenetic regulation and mRNA translation and identifies components that comprise unexpected therapeutic targets for PDAC.

Introduction:Proinflammatory cytokines, produced as an immune response in severe acute respiratory syndrome-coronavirus 2 infection, activate the coagulation cascade as well. In this study, we investigated the difference in the clinical course of patients who had been already using anti-thrombotic therapy before coronavirus disease-2019 (COVID-19) for any reason compared to the group who had not.Methods:In this retrospective, multicenter study; patients who were hospitalized between March 11 and July 1, 2020 were divided into two main groups as who had been on anti-thrombotic therapy for any indication use previously at the time of admission or who had not been on anti-thrombotic therapy at the time of admission, and their selected clinical parameters were compared.Results:After analyzing the study population of 124 patients with a homogeneous distribution in terms of age and gender, the comparison of anti-thrombotic users and non-users showed no significant difference in hospitalization. There was a statistically significant decrease in mechanical ventilation apply rate, intensive care unit duration and mortality rate between the group using anti-thrombotic compared to the group not using it (p

Abstract The FLT3 inhibitor gilteritinib has clinical activity in patients with FLT3‐mutated (FLT3mut+) relapsed/refractory (R/R) acute myeloid leukemia (AML). The impact of FLT3 mutation clearance and the achievement of composite complete remission (CRc) and complete remission/complete remission with partial hematologic recovery (CR/CRh) on overall survival (OS) in patients with FLT3mut+ R/R AML treated with single‐agent gilteritinib in a phase 1/2 trial were evaluated. Using next‐generation sequencing, a FLT3‐ITD variant allele frequency of ≤10−4 was used to define FLT3‐ITD clearance in patients with no morphologic leukemia (ie, CRc). A total of 108 patients with FLT3‐ITD‐positive (FLT3‐ITD+) R/R AML were analyzed; 95 of these patients had received ≥80‐mg/day gilteritinib. Ten of the 95 patients had FLT3‐ITD clearance; eight of these 10 patients achieved CRc and were considered negative for measurable residual disease. There was a trend toward longer OS in patients who attained CRc with FLT3‐ITD clearance (131.4 weeks) versus those who achieved CRc and did not have FLT3‐ITD clearance (n = 41; 43.3 weeks; HR = 0.416; p = 0.066). Among patients treated with ≥80‐mg/day gilteritinib who achieved CR/CRh (n = 24), seven had FLT3‐ITD clearance. Among patients who received 120‐mg/day gilteritinib, those who achieved CR/CRh had a longer median OS (70.6 weeks) and higher 52‐week survival probability (66.7%) than patients who did not achieve CR/CRh (n = 71; median OS, 41.7 weeks; 52‐week survival probability, 20.2%). Overall, these data suggest that gilteritinib can induce deep molecular responses in patients with FLT3‐ITD+ R/R AML, and in the setting of CRc or CR/CRh, these responses may be associated with prolonged survival.

PurposeThere is a major shortage of reliable early detection methods for pancreatic cancer in high-risk groups. The focus of this preliminary study was to use Time Intensity-Density Curve (TIDC) and Marley Equation analyses, in conjunction with 3D volumetric and perfusion imaging to demonstrate their potential as imaging biomarkers to assist in the early detection of Pancreatic Ductal Adenocarcinoma (PDAC).Experimental DesignsA quantitative retrospective and prospective study was done by analyzing multi-phase Computed Tomography (CT) images of 28 patients undergoing treatment at different stages of pancreatic adenocarcinoma using advanced 3D imaging software to identify the perfusion and radio density of tumors.ResultsTIDC and the Marley Equation proved useful in quantifying tumor aggressiveness. Perfusion delays in the venous phase can be linked to Vascular Endothelial Growth Factor (VEGF)-related activity which represents the active part of the tumor. 3D volume analysis of the multiphase CT scan of the patient showed clear changes in arterial and venous perfusion indicating the aggressive state of the tumor.ConclusionTIDC and 3D volumetric analysis can play a significant role in defining the response of the tumor to treatment and identifying early-stage aggressiveness.

Objectives:Vagal nerve stimulator is an effective treatment option for the medical treatment of the resistant-epilepsies. Surgical complication risks, as well as device-dependent risks, are also present. In this study, we aimed to draw attention to lead fractures from device-dependent complications.Methods:Between March 2005 and March 2015, patients who had vagal nerve stimulator implantation were screened in our clinic, and patients with lead fractures were included in this study.Results:Vagal nerve stimulator implants were implanted to over 170 patients in our clinic, and 11 of them were found to have lead fractures. They were all taken to revision surgery.Conclusion:Although lead fractures are not common, they form 11% of the device-dependent complications. High seizure severity, frequent frequency, long seizures and trauma may cause lead fractures.

Background: We conducted a first-in-human dose-escalation study with the oral FASN inhibitor TVB-2640 to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), as monotherapy and with a taxane. Methods: This completed open-label outpatient study was conducted at 11 sites in the United States and United Kingdom. Patients with previously-treated advanced metastatic solid tumors and adequate performance status and organ function were eligible. TVB-2640 was administered orally daily until PD. Dose escalation initially followed an accelerated titration design that switched to a standard 3 + 3 design after Grade 2 toxicity occurred. Disease-specific cohorts were enrolled at the MTD. Statistical analyses were primarily descriptive. Safety analyses were performed on patients who received at least 1 dose of study drug. (Clinicaltrials.gov identifier NCT02223247) Findings: The study was conducted from 21 November 2013 to 07 February 2017. Overall, 136 patients received TVB-2640, 76 as monotherapy (weight-based doses of 60 mg/m2 to 240 mg/m2 and flat doses of 200 and 250 mg) and 60 in combination, (weight-based doses of 60 mg/m2 to 100 mg/m2 and flat dose of 200 mg) (55 paclitaxel, 5 docetaxel). DLTs with TVB-2640 were reversible skin and ocular effects. The MTD/RP2D was 100 mg/m2. The most common TEAEs (n,%) with TVB-2640 monotherapy were alopecia (46; 61%), PPE syndrome (35; 46%), fatigue (28; 37%), decreased appetite (20; 26%), and dry skin (17; 22%), and with TVB-2640+paclitaxel were fatigue (29 ; 53%), alopecia (25; 46%), PPE syndrome (25; 46%), nausea (22; 40%), and peripheral neuropathy (20; 36%). One fatal case of drug-related pneumonitis occurred with TVB-2640+paclitaxel; no other treatment-related deaths occurred. Target engagement (FASN inhibition) and inhibition of lipogenesis were demonstrated with TVB-2640. The disease control rate (DCR) with TVB-2640 monotherapy was 42%; no patient treated with monotherapy had a complete or partial response (CR or PR). In combination with paclitaxel, the PR rate was 11% and the DCR was 70%. Responses were seen across multiple tumor types, including in patients with KRASMUT NSCLC, ovarian, and breast cancer. Interpretation: TVB-2640 demonstrated potent FASN inhibition and a predictable and manageable safety profile, primarily characterized by non-serious, reversible adverse events affecting skin and eyes. Further investigation of TVB-2640 in patients with solid tumors, particularly in KRASMUT lung, ovarian, and breast cancer, is warranted. Funding: This trial was funded by 3-V Biosciences, Inc. (now known as Sagimet Biosciences Inc.).

Background We assessed the safety, efficacy, and pharmacokinetics of the transforming growth factor beta (TGFβ) receptor inhibitor galunisertib co-administered with the anti-programmed death-ligand 1 (PD-L1) antibody durvalumab in recurrent/refractory metastatic pancreatic cancer previously treated with ≤2 systemic regimens.Methods This was a two-part, single-arm, multinational, phase Ib study. In a dose-finding phase, escalating oral doses of galunisertib were co-administered on days 1–14 with fixed-dose intravenous durvalumab 1500 mg on day 1 every 4 weeks (Q4W), followed by an expansion cohort phase.Results The galunisertib recommended phase II dose (RP2D) when co-administered with durvalumab 1500 mg Q4W was 150 mg two times per day. No dose-limiting toxicities were recorded. Among 32 patients treated with galunisertib RP2D, 1 patient had partial response, 7 had stable disease, 15 had objective progressive disease, and 9 were not evaluable. Disease control rate was 25.0%. Median overall survival and progression-free survival were 5.72 months (95% CI: 4.01 to 8.38) and 1.87 months (95% CI: 1.58 to 3.09), respectively. Pharmacokinetic profiles for combination therapy were comparable to those published for each drug. There was no association between potential biomarkers and treatment outcomes.Conclusion Galunisertib 150 mg two times per day co-administered with durvalumab 1500 mg Q4W was tolerable. Clinical activity was limited. Studying this combination in patients in an earlier line of treatment or selected for predictive biomarkers of TGFβ inhibition might be a more suitable approach.Trial registration number ClinicalTrials.gov identifier: NCT02734160.

Abstract: Internal tandem duplications in fms-like tyrosine kinase 3 (FLT3-ITDs) are common in acute myeloid leukemia (AML) and confer a poor prognosis. A sensitive and specific assay for the detection of minimal residual disease (MRD) in FLT3-ITD mutated AML could guide therapy decisions. Existing assays for MRD in FLT3-ITD AML have not been particularly useful because of limited sensitivity. We developed a sensitive and specific MRD assay for FLT3-ITD mutations using next-generation sequencing. The initial validation of this assay was performed by spiking fixed amounts of mutant DNA into wild-type DNA to establish a sensitivity of detection equivalent to ≥1 FLT3-ITD–containing cell in 10 000, with a minimum input of 100 000 cell equivalents of DNA. We subsequently validated the assay in bone marrow samples from patients with FLT3-ITD AML in remission. Finally, we analyzed bone marrow samples from 80 patients with FLT3-ITD relapsed/refractory AML participating in a trial of a novel FLT3 inhibitor, gilteritinib, and demonstrated a relationship between the mutation burden, as detected by the assay, and overall survival. This novel MRD assay is specific and 2 orders of magnitude more sensitive than currently available polymerase chain reaction– or next-generation sequencing–based FLT3-ITD assays. The assay is being prospectively validated in ongoing randomized clinical trials.

In this report, we describe a patient with a subvalvular membrane on the left ventricular outflow tract. Discrete subvalvular membrane is a cause of left ventricular outflow tract narrowing. Multidetector computerised tomography can demonstrate the anatomical three-dimensional view of this region and guide for surgery. [ABSTRACT FROM AUTHOR]

Abstract Background ASP3026 is a second-generation anaplastic lymphoma kinase (ALK) inhibitor that has potent in vitro activity against crizotinib-resistant ALK-positive tumors. This open-label, multicenter, first-in-human phase I study ( NCT01284192 ) assessed the safety, pharmacokinetic profile, and antitumor activity of ASP3026. Methods Advanced solid tumor patients received oral ASP3026 in 3 + 3 dose-escalation cohorts at doses of 25–800 mg once daily in 28-day cycles. The endpoints were to identify the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the pharmacokinetic profile of ASP3026. A phase Ib expansion cohort enrolled patients with metastatic, crizotinib-resistant ALK-positive solid tumors at the RP2D, and response was evaluated by RECIST 1.1. Results The dose-escalation cohort enrolled 33 patients, including three crizotinib-resistant, ALK-positive patients, and the dose-expansion cohort enrolled another 13 crizotinib-resistant, ALK-positive non-small cell lung cancer (NSCLC) patients. ASP3026 demonstrated both linear pharmacokinetics and dose-proportional exposure for area under the plasma concentration–time curve and maximum concentration observed with a median terminal half-life of 35 h, supporting the daily dosing. Grade 3 rash and elevated transaminase concentrations were dose-limiting toxicities observed at 800 mg; hence, 525 mg daily was the MTD and RP2D. The most common treatment-related adverse events were nausea (38 %), fatigue (35 %), and vomiting (35 %). Among the 16 patients with crizotinib-resistant ALK-positive tumors (15 NSCLC, 1 neuroblastoma), eight patients achieved partial response (overall response rate 50 %; 95 % confidence interval 25–75 %) and seven patients (44 %) achieved stable disease. Conclusions ASP3026 was well tolerated and had therapeutic activity in patients with crizotinib-resistant ALK-positive advanced tumors. Trial registration ClinTrials.gov: NCT01284192

Introduction: The effect of pump flow type on perfusion in coronary surgery using cardiopulmonary bypass (CPB) is discussed. We aimed to evaluate the effect of pump flow type on cognitive functions with neurocognitive function tests., Methods: One hundred patients who underwent isolated coronary artery bypass surgery between November 2020 and July 2021 were divided into two equa groups. Groups were formed according to pump flow type pulsatile (Group 1) and non-pulsatile (Group 2). Clock drawing test (CDT) and standardized mini mental test (SMMT) were performed on the patients in both groups in the preoperative period, on the 1st preoperative day, and on the day before discharge. Neurocognitive effects were compared with all follow-up parameters., Results: There was no difference between the groups in terms of demographic data and in terms of neurocognitive tests performed before the operation. SMMT on postoperative day 1 (Group I: 27.64 ± 1.05; Group II: 24.44 ± 1.64; P=0.001) and CDT (Group I: 5.4 ± 0.54; Group II: 4 .66 ± 0.52; P=0.001), and SMMT on the day before discharge (Group I: 27.92 ± 1.16; Group II: 24.66 ± 1.22; P=0.001) and CDT (Group I: 5 It was calculated as .66 ± 0.48; Group II: 5.44 ± 0.5; P=0.001). The duration of intensive care and hospitalization were higher in the non-pulsatile group., Conclusion: We think that the type of pump flow used in coronary artery bypass surgery using CPB is effective in terms of neurocognitive functions and that pulsatile flow makes positive contributions to this issue.

Background: The results of the use of del-Nido(DN) solution using a different method or crystalloid blood cardioplegia in coronary bypass patients were compared. We aimed to investigate the effects on intraoperative and postoperative arrhythmias, arrhythmia durations and early results., Methods: The study included 175 patients using crystalloid blood cardioplegia (Group 1) and 150 patients using DN solution(Group 2). In the DN group, 75% of the calculated plegia dose was given first. the remaining part was applied by giving from grafts. Intraoperative/postoperative data were compared., Results: There was no significant difference between the groups in terms of demographic characteristics. Preop troponin level was similar.(p = 0.190) However, there was a statistical difference between the postoperative 6th hour.(p = 0.001) There was no difference in troponin values at the postoperative 24th hour. (p = 0.631) Spontaneous rhythm occurred at the cardiopulmonary by pass (CPB) weaning stage in most of the patients in Group 2 (95.3%). Although the need for temporary pacing was less in Group 2, it was not significant.(p = 0.282) No patient required permanent pacing. CPB duration, cross clamp times and intraoperative glucose levels, intensive care follow-up times and hospitalization times were found to be shorter in Group 2. Although the postoperative atrial fibrillation frequency was similar (p = 0.261), the time to return to sinus was lower in Group 2.(p = 0.001)., Conclusion: The use of DN cardioplegia solution provides significant positive contributions to avoid arrhythmias compared to crystalloid blood cardioplegia. DN solution applied with this method may contribute to reducing the anxieties associated with its use in isolated coronary artery bypass surgery., (© 2024. The Author(s).)

The carotid body tumor (CBT) is a rare paraganglioma neoplasm that often occurs in the head and neck anatomical region. Carotid angiography continues to be widely regarded as the preferred diagnostic method for this particular malignancy. Surgical intervention has been widely acknowledged as the primary approach for managing CBTs. However, the resection of CBTs poses significant technical challenges due to its specific anatomical position. To mitigate the incidence of intraoperative and postoperative challenges, we have conducted a comprehensive review of both domestic and international literature to consolidate the surgical approach and strategies for preventing and managing complications associated with this particular tumor., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kilic et al.)

One kind of coronary artery disease that is uncommon is coronary artery aneurysm (CAA). According to angiographic reports, the incidence of coronary artery aneurysms ranges from 1.5% to 4.9%, with a higher frequency in men. A patient with both coronary heart disease and an aneurysm in the right coronary artery (RCA) underwent a successful simultaneous coronary bypass together with an aneurysmal reconstruction procedure., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Jalalzai et al.)

Background: When acute coronary syndrome patients necessitate immediate revascularization, heart-on-pump coronary artery bypass grafting may be regarded as a viable substitute for conventional on-pump surgery. Our clinical experience and initial outcomes of heart-on-pump coronary surgery in patients with acute coronary syndrome are detailed in this article., Method: This research endeavor was a retrospective analysis that spanned the years March 2011 to August 2023. The sample size comprised 2816 patients who had undergone coronary artery surgery. During this period, the same surgical team performed coronary artery bypass surgery on 411 of these patients, who underwent beating heart surgery while on cardiopulmonary bypass support and without cardioplegic arrest; this was done under emergency conditions., Result: 9.3 ± 2.2 hours elapsed between the initiation of acute myocardial infarction and the commencement of coronary artery bypass grafting (CABG). A mean of 4.0 grafts was applied (2.2 ± 1.1). Mortality in hospitals was calculated for sixteen patients. Following surgery, twenty-six patients developed an inadequate cardiac output syndrome. Despite having renal dysfunction, none of the eight individuals needed hemodialysis. The mean duration of stay in intensive care was 3.2 (2.2 ± 1.1) days, while the mean length of hospitalization was 9.2 (4.3 ± 2.4) days., Conclusion: We believe that for high-risk patients with multivascular coronary artery disease who require an emergency coronary artery bypass graft, on-pump beating heart revascularization could be a viable option.

Background: Graft patency is the most important factor in coronary artery bypass surgery. This study aimed to compare the relationship between three different surgical methods and transit time flow measurement (TTFM), which is used to detect technical problems in anastomoses performed during coronary artery bypass graft operations and to correct them if necessary., Methods: A total of 110 patients undergoing isolated coronary artery bypass surgery were analysed. Of these patients, 48 were operated on by inducing cardiopulmonary arrest (group 1), 33 were operated on without inducing cardiac arrest (group 2) during cardiopulmonary bypass surgery, and 29 underwent surgery on the off-pump beating heart (group 3). TTFMs were performed on all the patients' grafts. Additional surgical intervention requirements, the need for intra-operative and postoperative inotropic support, and all postoperative follow-up data were compared., Results: In total, 110 patients were measured for 301 grafts. Due to insufficient measurements performed on these patients, additional surgical intervention was performed on five grafts in group 1, five grafts in group 2, and seven grafts in group 3. These interventions enabled a normal flow rate to be achieved. The number of grafts that required revision was highest in group 3. There was no difference between the groups in terms of demographic data, EuroSCORE II, preoperative ejection fraction, postoperative complications and mortality rate., Conclusion: TTFM is important for detecting technical problems in grafts. We believe that all surgical methods can be applied more safely by controlling graft flow.

The aim of this approach is to establish a relation between ecological footprint and technological innovations by using panel data techniques and taking Union for the Mediterranean member countries as the case. On the one hand, the Mediterranean region is an alarming region when it comes to environmental degradation; on the other hand, existing intergovernmental organizations such as the Union for the Mediterranean may provide a sound ground to take common action among all members against such a degradation. The approach takes eleven member countries from the Union for the Mediterranean (Bosnia and Herzegovina, France, Greece, Israel, Italy, Jordan, Morocco, Portugal, Spain, Tunisia, Türkiye) and observes them for the time frame 1992-2020. By using panel unit root tests and cross-sectional dependency tests, the data is being analyzed for further evaluation using mean group, common correlated effect mean group, and augmented mean group analysis. Regarding the observed variables, we could not identify a common trend for these eleven countries. For the sample of eleven countries, the impact of technological innovations was not significant, but country-level augmented mean group analysis results indicated that for Portugal, this impact was significant and positive., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)