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Introduction: Early detection of breast cancer plays a pivotal role in the outcome of the disease. Diagnostic modalities encompass radiological and pathological findings. The aim of this study is to evaluate the correlation between the results of these two modalities in a tertiary hospital. Materials and Methods: From a total of 180 patients, 203 ultrasound-guided breast core needle biopsies (US-CNBs) were included in this study over a period of a year (May 2015 - May 2016). All clinical parameters, the site of the biopsy, the size of the needle, the radiological findings, the pathological diagnoses as well as all available follow-up data were reviewed. The concordance between the radiological and pathological results was studied and a statistical analysis conforms to the Pearson Chi-square test was applied. Results: The majority of our patients were above 40 years of age. A strong and statistically significant association was noted between radiological findings and histopathological results (Pearson's Chi-square test = 186.28, P ≤ 0.0001) with only four discordant cases (1.97%). This discrepancy was not statistically associated with age, site of biopsy, needle size, or number of cores obtained (P = 0.621, P = 0.584, P = 0.786, and P = 0.478, respectively). Conclusions: US-CNB is an accurate method in the diagnosis of breast lesions. Radiological and pathological correlation is of utmost importance in relation to patient's care and to reduce false rates. Follow-up of concordant benign lesions is essential. In addition, the importance of a multidisciplinary breast conference during which input from all teams caring for the patient is strongly emphasized.

Thrombotic thrombocytopenic purpura (TTP)/Hemolytic–uremicsyndrome (HUS) is a syndrome characterized by thrombocytopenia,microangiopathic hemolytic anemia, fever, renal failure and neurologic manifestation.Almost all cases are idiopathic. However, secondary TTP/HUSassociated with viral, bacterial and mycobacterial infections, drugs,connective tissue disease, solid tumors, bone marrow transplantationand pregnancy have been described. Early relapse associated withinfection is a rare occurrence. The patient we report had a classic caseof postdiarrheal TTP/HUS that responded to plasmapheresisbut relapsed during treatment as reflected by the increased schistocytosis,decreased hematocrit, increased lactate dehydrogenase, and decreased platelet counts. This relapse may be attributed to Acinetobacteranitratus bacteremia, secondary to central line infection. Administrationof antimicrobial treatment resulted initially in a mild improvement.However, this was followed by a fatal relapse. The importance ofmonitoring the possible bacterial colonization of an indwellingcatheter is thus emphasized. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, and neurologic symptoms. TTP is associated with many diseases and several therapeutic drugs. We report the rare case of a patient with rheumatoid arthritis who developed TTP that was not associated with drug therapy, 18 months after the onset of rheumatoid arthritis. She recovered from the TTP following daily sessions of therapeutic plasma exchange (TPE) with fresh frozen plasma replacement and glucocorticoid therapy. Recent pathogenic mechanisms are reviewed as they relate to von Willebrand factor. In this report of the rare association of TTP with rheumatoid arthritis, an immediate relationship is likely because both are of an immune nature. Awareness of the possible development of TTP in rheumatoid arthritis is important for early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates targeting folate receptor alpha (FRα) are a promising treatment for platinum-resistant ovarian cancer (OC) with high FRα expression. Challenges persist in accurately assessing FRα expression levels. Our study aimed to better elucidate FRα gene expression and identify mRNA signatures in OC. We pooled OC gene expression data from 16 public datasets, encompassing 1832 OC and 30 normal ovarian tissues. Additional data included DNA copy number and methylation data from TCGA and protein data from 363 cancer cell lines from the Broad Institute Cancer Cell Line Encyclopedia. FOLR1 mRNA expression was significantly correlated with protein expression in pan-cancer cell lines and ovarian cancer cell lines. FOLR1 expression was higher in OC samples than in normal ovarian tissues (OR = 3.88, p = 6.97 × 10 -12 ). Patients with high FOLR1 expression were more likely to be diagnosed with serous histology, FIGO stage III-IV, and high-grade tumors; however, nearly similar percentages of patients with low FOLR1 expression were also diagnosed with these features. FOLR1 mRNA expression was not correlated with platinum sensitivity or complete surgery, nor with prognosis. However, we identified a 187-gene signature associated with high FOLR1 expression that was significantly associated with improved survival (HR = 0.71, p = 1.18 × 10 -6 ), independently from clinicopathological features. We identified a gene expression signature correlated to high FRα expression and OC prognosis, which may be used to refine therapeutic strategies targeting FRα in OC. These findings warrant validation in larger cohorts.

There is a lack of biomarkers to predict outcome following initial treatment in patients with high-grade ovarian cancer. We hypothesized that monitoring TP53 mutation ( TP53m ) in circulating tumor DNA (ctDNA) could be a tumor-specific biomarker. Patients enrolled in a prospective study (NCT03010124) consented to analysis of biological samples through the disease course. ctDNA was extracted and analyzed to detect the presence of TP53m Next-generation sequencing was performed on tumor tissue to detect TP53m and on whole blood to detect clonal hematopoiesis of indeterminate potential (CHIP).A total of 102 samples were sequentially collected from 26 patients. ctDNA was detected in all patients at diagnosis. The same TP53m was found in ctDNA and tumor tissue in 77% of patients. TP53m in ctDNA was not CHIP related. During neoadjuvant chemotherapy, increasing ctDNA was associated with failure to achieve complete interval cytoreductive surgery in 60% of patients. Rising ctDNA or de novo TP53m seemed to be associated with a trend for worst survival compared with decrease or complete clearance: progression-free survival 10 versus 26.5 months, HR 3.2. Despite macroscopically complete surgery, 30% of patients had detectable ctDNA post-operatively and had worse survival than those with undetectable ctDNA. Monitoring TP53m in ctDNA during chemotherapy or after surgery could help guide the best adjuvant therapy., Competing Interests: Competing interests: MK: advisory boards/honoraria: GSK, AstraZeneca; travel, accommodations: Pfizer, GSK, Eisai. ND: travel, accommodations: GSK; advisory boards/honoraria: GSK, AstraZeneca, MSD, Clovis Oncology, EISAI. KH: shareholder/stockholder/stock options, full/part-time employment: Inivata. ER: honoraria: AstraZeneca (Inst), Roche (Inst), BMS (Inst), GlaxoSmithKline (Inst), Clovis Oncology (Inst); consulting or advisory role: AstraZeneca; research funding: AstraZeneca (Inst); travel, accommodations, expenses: AstraZeneca, BMS. JBM : honoraria: Jazz Pharmaceuticals, Astellas Pharma; consulting or advisory role: AbbVie, Servier; travel, accommodations, expenses: AbbVie. AL: honoraria (self): Medscape; AZ, Clovis, GSK, Kephren; advisory/consultancy: AZ, Clovis, GSK, Biocad, Ability Pharma, Merck Serono, Tesaro, MSD, Seattle Genetics, Gamamabs, Gritstone; research grant/funding (self): Inivata, Sanofi, AZ, OSE Immuno; travel/accommodation/expenses: AZ, Roche, Clovis, Tesaro. All other authors have declared no conflicts of interest., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Mullerian adenosarcoma is a rare malignant biphasic tumor. The mesenchymal component may be low or high grade, with or without sarcomatous overgrowth (SO). Little is known about the molecular heterogeneity of these tumors. In this study, we aim to reclassify a large retrospective monocentric cohort of uterine adenosarcomas according to tumor grade and SO, to evaluate the clinical significance of pathological classification and to correlate with copy-number variations inferred from single nucleotide polymorphism array. Of the 67 uterine adenosarcomas, 18 (26.9%) were low grade without SO, 7 (10.4%) low grade with SO, 8 (11.9%) high grade without SO and 34 (50.7%) high grade with SO. SO, necrosis and RMS were more frequent in high grade than low grade adenosarcomas (p < 0.001). Low-rank test showed that recurrence-free survival was significantly shortened in high grade than low grade adenosarcomas (p = 0.035) and SO was associated with shortened overall and recurrence-free survival (p = 0.038 and p = 0.009, respectively). High-grade tumors displayed complex genomic profiles with multiple segmental losses including TP53, ATM and PTEN genes. The median genomic index was significantly higher in high grade than low grade tumors (27 [3-60] vs 5,3 [0-16], p < 0.0001) and was significantly higher in presence of SO in low grade tumors (12,8 [10-16] vs 2,6 [0-10], p = 0.0006). We propose to report sarcomatous overgrowth with the tumor grade for prognostication in adenosarcoma and representative sampling is crucial for evaluation of these histological criteria., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Breast cancer (BC) incidence increases with age, particularly in HR-positive/HER2-negative subtypes. Cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6is) alongside endocrine therapy (ET) have emerged as promising treatments for HR-positive/HER2-negative advanced and early BC. However, their efficacy, safety, and impact on quality of life (QoL) in older and frail patients remain underexplored., Methods: This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC., Results: Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients' daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment., Conclusion: Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, the Gustave Roussy Cancer Center introduced teleconsultation via telephone, as an alternative to face-to-face consultation to reduce patient hospital visits. This study was designed to assess patient and doctor satisfaction with this modality of care in oncology patient care during the period of the pandemic and beyond., Methods: We designed two questionnaires based on validated scores to assess satisfaction from teleconsultation in patients (EORTC OUT-PATSAT 35 and Telemedicine Satisfaction Questionnaire [TSQ] scores) and doctors (Telehealth Usability Questionnaire [TUQ]), and anxiety levels in both groups (anxiety section of the Hospital Anxiety and Depression Scale [HADS], HADS-A). These were electronically sent to patients and doctors with experience of at least one remote consultation during the first wave of the COVID-19 pandemic., Results: 239 patients and 32 doctors were eligible for the analyses. In the patient group, the mean satisfaction scores were 79.5 (SD 18.1) and 74.92 (SD 15.3) for EORTC OUT-PATSAT 35 and TSQ, respectively. In the doctor group, the mean satisfaction scores were 67.1 (SD 12.7) and 64.9 (SD 13.9) for TUQ and TUQ for Skype for Business, respectively. 65.7% of patients and 81.2% of doctors had no/low anxiety. Univariable analyses in patients showed correlation of the EORTC OUT-PATSAT 35 and TSQ scores with anxiety and gender, with lower mean scores in women compared to men. Multivariable analysis showed correlation of the EORTC OUT-PATSAT 35 and TSQ scores to anxiety in both patients and doctors., Conclusions: Teleconsultation via telephone is an acceptable modality of care for oncology patients, with high satisfaction from its implementation during the pandemic reported by patients and doctors. This was consistent across responder groups with different characteristics. An individualized approach to patients should be implemented for the safe and effective use of teleconsultation in oncology beyond the pandemic.

Introduction: Premenstrual symptoms encompass a range of physical, emotional, and behavioral changes that cyclically occur before menstruation. Childhood abuse has been associated with subsequent mental health challenges, yet its relationship with exacerbating premenstrual symptoms remains an understudied area. Furthermore, suicidal ideation often emerges from traumatic backgrounds such as child abuse, creating another layer of complexity. Given the rising suicide rates in Lebanon, and the concurrent increase in reported child abuse cases, this research focuses on the role of suicidal ideation as a mediator between child abuse and premenstrual syndrome., Methods: This cross-sectional study involved 915 female university students in Lebanon. Participants completed an online questionnaire encompassing demographic details, health lifestyle, the Premenstrual Symptoms Screening Tool (PSST), Columbia-Suicide Severity Rating Scale (C-SSRS), and Child Abuse Self Report Scale (CASRS-12). The mediation analysis was conducted using PROCESS MACRO v3.4 model 4; three pathways derived from this analysis: pathway A from the independent variable to the mediator, pathway B from the mediator to the dependent variable, Pathway C indicating the direct effect from the independent to the dependent variable., Results: The results of the mediation analysis showed that suicidal ideation mediated the association between all types of child abuse and the presence of PMS. Higher psychological (Beta = 0.21; p < 0.001), neglect (Beta = 0.02; p = 0.017), physical (Beta = 0.19; p < 0.001) and sexual (Beta = 0.20, p < 0.001) child abuse were significantly associated with higher suicidal ideation, which was significantly associated with the presence of PMS (Beta = 0.38, p = 0.001; Beta = 0.57, p < 0.001; Beta = 0.45, p < 0.001; and Beta = 0.50, p < 0.001) respectively. Finally, higher psychological (Beta = 0.17, p < 0.001), physical (Beta = 0.11, p = 0.024), but not sexual (Beta = 0.07, p = 0.198) child abuse was directly and significantly associated with the presence of PMS, whereas higher neglect (Beta = -0.06, p = 0.007) was significantly associated lower odds of having PMS., Conclusion: This study highlights the mediating role of suicidal ideation in the complex association between different types of childhood abuse and premenstrual symptoms. The findings emphasize the need for trauma-informed care and tailored interventions to address the diverse impact of these factors. Recognizing the intricate relationships between child abuse, suicidal ideation, and PMS can aid healthcare providers in comprehensively addressing young women's mental and reproductive well-being. Trauma-informed care, tailored interventions and awareness of potential connections between childhood maltreatment are essential in managing these complex challenges., (© 2024. The Author(s).)

Fasting has gained significant attention in recent years for its potential health benefits in various body systems. This review aims to comprehensively examine the effects of fasting on human health, specifically focusing on its impact on different body's physiological systems. The cardiovascular system plays a vital role in maintaining overall health, and fasting has shown promising effects in improving cardiovascular health markers such as blood pressure, cholesterol levels, and triglyceride levels. Additionally, fasting has been suggested to enhance insulin sensitivity, promote weight loss, and improve metabolic health, thus offering potential benefits to individuals with diabetes and metabolic disorders. Furthermore, fasting can boost immune function, reduce inflammation, enhance autophagy, and support the body's defense against infections, cancer, and autoimmune diseases. Fasting has also demonstrated a positive effect on the brain and nervous system. It has been associated with neuroprotective properties, improving cognitive function, and reducing the risk of neurodegenerative diseases, besides the ability of increasing the lifespan. Hence, understanding the potential advantages of fasting can provide valuable insights for individuals and healthcare professionals alike in promoting health and wellbeing. The data presented here may have significant implications for the development of therapeutic approaches and interventions using fasting as a potential preventive and therapeutic strategy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Homologous recombination deficiency (HRD) is closely related to PARP inhibitor (PARPi) benefit in ovarian cancer. The capacity of BRCA1 promoter methylation to predict prognosis and HRD status remains unclear. We aimed to correlate BRCA1 promoter methylation levels in patients with high-grade ovarian cancer to HRD status and clinical behavior to assess its clinical relevance., Experimental Design: This is a retrospective monocentric analysis of patients centrally tested for genomic instability score (GIS) by MyChoice CDx (Myriad Genetics). The detection of BRCA1 promoter methylation and quantification of methylation levels were performed by quantitative droplet digital PCR methodology. High BRCA1 methylation was defined as ≥70% and deemed to be associated with homozygous silencing., Results: Of 100 patients, 11% harbored a deleterious BRCA1/2 mutation. GIS was considered positive (score ≥ 42) for 52 patients and negative for 48 patients. Using a 70% cutoff, 19% (15/79) of BRCA wild-type ovarian cancer had high BRCA1 methylation levels. All of the highly methylated tumors were classified as HRD, achieving a positive predictive value of 100%. We detected 14% (11/79) low-methylated tumors (1%-69%), and all of them were also classified as HRD. Mean GIS was 61.5 for BRCAmut, 66.4 for high-BRCAmeth, 58.9 for low-BRCAmeth, and 33.3 for BRCAwt unmethylated (P < 0.001). Low methylation levels detected in samples previously exposed to chemotherapy appeared to be associated with poor outcome post-platinum., Conclusions: Patients with ovarian cancer with high levels of BRCA1 hypermethylation are very likely to have high GIS and therefore represent good candidates for PARPi treatment. These results may be highly relevant to other tumor types for HRD prediction. See related commentary by Garg and Oza, p. 2957., (©2023 American Association for Cancer Research.)

Background: PARP inhibitors (PARPi) have revolutionized the management of high-grade epithelial ovarian cancer (HGOC) treatment. However, a significant number of patients relapse or progress under PARPi, leading to the introduction of a new line of systemic therapy such as chemotherapy. In patients with a limited number of metastatic sites at progression, -referred to as an oligometastatic progression- a potential indication for local therapy followed by re-introduction or continuation of PARPi treatment rather than initiating a new line of chemotherapy could be proposed. However, the impact of such strategies on progression free survival (PFS) in these patients remains unknown., Methods: This international multicenter retrospective study evaluated the efficacy of PARPi continuation or re-introduction in patients with HGOC after local treatment for oligometastatic progression. The main objective was to assess PFS under PARPi after local therapy (PFS post-LT). Secondary objectives included safety and overall survival (OS)., Results: 74 patients were identified in 20 centers between April 2020 and November 2021. 65% of patients were BRCA mutated and 92% had received ≥2 lines of prior systemic chemotherapy before the initial introduction of PARPi. Main progression sites were lymph nodes (42%), peritoneum (27%), liver (16%), other visceral (16%) and abdominal wall (4%). Local therapies included radiotherapy (45%), surgery (43%), both (7%), percutaneous thermal ablation (4%) or chemoembolization (1%). Median PFS post-LT was 11.5 months [95% CI 7.4; 17.2]. After a median follow up of 14.8 months, 6 patients (8.1%) discontinued PARPi due to toxicity. The 1-year overall survival rate was 90.7% [95% CI 79.1; 96.0]., Conclusions: With close to one year without progression or introduction of a new line of systemic therapy, this study reports the feasibility and potential benefit of this original strategy in patients with oligometastatic progression under PARPi., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Olaparib, a poly(ADP-ribose) polymerase inhibitor, was approved by the European Commission in June 2019, following the results of the SOLO-1/GOG 3004 trial as maintenance monotherapy in adult patients with BRCA-mutated epithelial ovarian cancer., Objective: This study aimed to provide a descriptive analysis of the first real-world data from patients with BRCA-mutated ovarian cancer who received olaparib as first-line maintenance monotherapy in the French cohort Temporary Authorisation for Use (Autorisation Temporaire d'Utilisation de cohorte, ATUc) programme from 11 March, 2019 to 16 January, 2020., Methods: Eligible patients were aged 18 years and over with confirmed epithelial ovarian, primary peritoneal or Fallopian tube cancer and a deleterious or suspected deleterious germline or somatic BRCA 1/2 mutation. Patients were in complete or partial clinical response at the end of first-line platinum-based chemotherapy. Olaparib maintenance therapy was initiated within 8 weeks of the patients' last dose of chemotherapy. Real-world data were collected through treatment access request forms completed by physicians. Clinical and safety data were collected monthly until the end of the ATUc programme., Results: A total of 107 centres in metropolitan France and the French Overseas Departments and Territories requested the inclusion for 238 patients, of whom 194 received maintenance olaparib. In total, 87.6% of the primary tumour locations were ovary, the most common histology was high-grade serous (93.0%) and the most common International Federation of Gynaecology and Obstetrics (Fédération Internationale de Gynécologie et d'Obstétrique) stage was IIIC (56.8%). BRCA testing was performed in routine practice, prior to inclusion into the ATUc programme. All patients had a BRCA mutation: 52.5% had a somatic mutation, 38.4% had a germinal mutation and 9.1% had germinal and somatic mutations. Twenty-four (12%) patients experienced serious adverse drug reactions at the last safety follow-up (17 February, 2020). The most common were anaemia (12 [6%] patients), neutropenia (3 [2%] patients) and thrombocytopenia (3 [2%] patients)., Conclusions: The rapid enrolment into the ATUc programme highlighted the strong unmet need for patients with ovarian cancer and a BRCA mutation in first-line maintenance treatment. Olaparib was well tolerated and no new safety signals were observed in this real-world patient population., (© 2023. The Author(s).)

Background: Endometriosis is a complex disease that affects approximately 10% of women of childbearing age. It is characterized by the presence of endometrial-like tissue outside the uterus and often results in symptoms such as pelvic pain and infertility. This condition may disturb mental health and decrease both the mental and physical health related quality of life of women. The aim of this study was to assess the emotional state and the intimate relational aspect of life in Lebanese women living with endometriosis., Methods: This is a case-control study that included 317 women (65 participants with endometriosis and 252 controls (1:3 ratio)). Participants completed an online survey that included questions related to endometriosis, Sexual Satisfaction Scale for Women, Couple Satisfaction Index, Perceived Partner Responsiveness Scale and the Depression, Anxiety and Stress Scale., Results: A significantly higher mean sexual satisfaction score was found in women without endometriosis compared to those with endometriosis (90.83 vs. 83.42; p = 0.006). No significant difference was found in terms of couple satisfaction, depression, anxiety, stress, and perceived partner responsiveness between the two groups. Higher couple satisfaction (Beta = 1.30) and perceived partner responsiveness (Beta = 0.16) were significantly associated with higher sexual satisfaction, whereas higher depression (Beta=-1.70) and having endometriosis compared to not (Beta=-6.51) were significantly associated with lower sexual satisfaction., Conclusion: This study validated the link between endometriosis and sexual satisfaction and invalidated the association between endometriosis and emotional state, as well as couple satisfaction and perceived partner responsiveness. Greater sexual satisfaction was, however, linked to greater perceived partner responsiveness and greater couple satisfaction, as well as decreased signs of depression, anxiety, and stress. More research is warranted to better understand how Lebanese women are coping with the disease and how clinicians may help them further., (© 2023. The Author(s).)

ATP, the power of all cellular functions, is constantly used and produced by cells. The enzyme called ATP synthase is the energy factory in all cells, which produces ATP by adding inorganic phosphate (Pi) to ADP. It is found in the inner, thylakoid and plasma membranes of mitochondria, chloroplasts and bacteria, respectively. Bacterial ATP synthases have been the subject of multiple studies for decades, since they can be genetically manipulated. With the emergence of antibiotic resistance, many combinations of antibiotics with other compounds that enhance the effect of these antibiotics have been proposed as approaches to limit the spread of antibiotic-resistant bacteria. ATP synthase inhibitors, such as resveratrol, venturicidin A, bedaquiline, tomatidine, piceatannol, oligomycin A and N,N-dicyclohexylcarbodiimide were the starting point of these combinations. However, each of these inhibitors target ATP synthase differently, and their co-administration with antibiotics increases the susceptibility of pathogenic bacteria. After a brief description of the structure and function of ATP synthase, we aim in this review to highlight therapeutic applications of the major bacterial ATP synthase inhibitors, including animal's venoms, and to emphasize their importance in decreasing the activity of this enzyme and subsequently eradicating resistant bacteria as ATP synthase is their source of energy.

Young oncologists around the globe face many challenges when it comes to their career and professional development. Aspects such as time management, work-life balance, career progression, and educational opportunities are only some of them. Professional societies have identified these challenges in this professional group and designed programs to tackle them specifically. The importance of this strategy cannot be overstated, as young oncologists, defined by most societies as oncologists under 40 years of age, compose almost 50% of the oncology workforce. On the other hand, recent surveys have shown that many young oncologists are considering alternative career paths due to burnout issues aggravated by the COVID-19 pandemic, on top of all other challenges. The virtual setting that has been forcedly introduced into our professional life has shortened distances between professionals and might have contributed to more accessible access to information and opportunities that some young oncologists could not profit from due to their traveling constraints. On the other hand, this virtual setting has shown us the asymmetries in opportunities for these professionals. Knowledgeable of all this, we summarize in this article some of the career and professional development offers available to all young oncologists, which we consider could help them deal with current and future challenges., (© 2022 S. Karger AG, Basel.)

Background: Numerous retrospective studies and reviews have reported a positive association between immune-related adverse events (irAEs) and survival in non-small cell lung cancer (NSCLC) and melanoma patients treated with immune checkpoint blockers (ICBs). However, some results are controversial and the studies, whose results converge, should be interpreted cautiously because most of them do not deal appropriately with the immortal-time bias. Here, we report an observational real-life study of the association between prospectively collected irAEs and survival of patients treated with ICBs while dealing with the immortal-time bias., Methods: Data from patients treated at Gustave Roussy from June 2014 to October 2017 with anti-PD-(L)1 antibodies for a melanoma or NSCLC have been prospectively collected in the REISAMIC database, a pharmacovigilance registry dedicated to irAEs. Adverse events of grade 2 and higher were collected prospectively. To study the association between the occurrence of irAEs and survival, we used both a landmark analysis and a Cox regression model with time-dependent covariate., Results: 577 patients were treated with anti-PD-(L)1 antibodies for melanoma (60.3 %) or NSCLC (39.7 %). The occurrence of an irAE was significantly associated with improved overall survival (OS): HR 0.56, 95 % CI [0.41; 0.75], p = 0.0001 and progression-free survival (PFS): HR 0.63, 95 % CI [0.47; 0.83], p = 0.001 using a Cox regression model with time-dependent covariate. In a 12-week landmark analysis, median OS was 21.2 months (95 % CI, 12.2 to 35.7) and 16.4 months (95 % CI, 12.4 to 21.3) p = 0.26 and median PFS was 14.3 months (95 % CI, 9.5 to 24.6) and 13.4 months (95 % CI, 10.2 to 18.3) p = 0.66, for patients with and without irAEs, respectively., Conclusions: In our real-life study of patients with melanoma and NSCLC treated with anti-PD-(L)1 antibodies, we confirm that irAEs are associated with improved survival using a time-varying Cox regression model. Analysis with a landmark method showed no difference in OS or PFS between patients who experienced irAE during the first 12 weeks of treatment and those who did not. Retrospective analysis and reviews including studies that do not deal with the immortal-time bias and studies insufficiently powered for a landmark analysis should be interpreted with caution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosure MK has nothing to declare. CO: honoraria/presentations: Ipsen Pharma, Roche, Medac; research support: Roche, Pharma Mar; travel grants: Ipsen, PharmaMar, Medac.

Introduction: Actionable somatic molecular alterations are found in 15% to 20% of NSCLC in Europe. NSCLC is a tumor observed in patients with germline TP53 variants causing Li-Fraumeni syndrome (LFS), but its somatic molecular profile is unknown., Methods: Retrospective study of clinical and molecular profiles of patients with NSCLC and germline TP53 variants., Results: Among 22 patients with NSCLC and LFS (n = 23 lung tumors), 64% were women, median age was 51 years, 84% were nonsmokers, 73% had adenocarcinoma histological subtype, and 84% were diagnosed with advanced-stage disease. These patients harbored 16 distinct germline TP53 variants; the most common was p.R158H (5/22; three in the same family). Personal and family histories of cancer were reported in 71% and 90% of patients, respectively. In most cases (87%, 13/15), lung cancer was diagnosed with a late onset. Of the 21 tumors analyzed, somatic oncogenic driver mutations were found in 19 of 21 (90%), EGFR mutations in 18 (exon 19 deletion in 12 cases, L858R in three cases, and G719A, exon 20 insertion, and missing mutation subtype, each with one case), and ROS1 fusion in one case. A PI3KCA mutation was concurrently detected at diagnosis in three EGFR exon 19-deleted tumors (3/12). The median overall survival was 37.3 months in 14 patients treated with EGFR inhibitors; seven developed resistance, five (71%) acquired EGFR-T790M mutation, and one had SCLC transformation., Conclusions: Driver oncogenic alterations were observed in 90% of the LFS tumors, mainly EGFR mutations; one ROS1 fusion was also observed. The germline TP53 variants and lung cancer carcinogenesis driven by oncogenic processes need further evaluation., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Aging is an important risk factor for cancers and is associated with poor prognosis. Weakness of the immune system, also called immunosenescence may occur with older age. The impact of aging on efficacy and safety of immune checkpoint blockers, such as anti-programmed death (ligand) PD-(L)1, remains undetermined. This study aims to evaluate the incidence of immune-related adverse events (irAEs) in patients aged 70 years or older than their younger counterparts., Methods: Patients with advanced solid tumors treated at Gustave Roussy with an anti-PD-(L)1 monotherapy between June 2014 and October 2017 were prospectively included within the dedicated irAEs pharmacovigilance registry REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie). The incidence of irAEs of grade ≥II was compared between patients aged ≥70 (old patients, OP) versus patients aged < 70 years (young patients, YP) using a chi-squared test. Survivals were estimated using the Kaplan-Meier method., Results: Among the 603 patients treated by anti-PD(L)1, 191 were ≥70 y.o (OP) and 424 < 70 y.o (YP). The median (range) age of OP and YP were respectively 77 (70-93) and 59 years old (17-69). A total of 165 irAEs occurred in these patients (103 grade II and 58 grade III-IV). The overall incidence of grade ≥II irAEs was higher in OP than in YP (33% versus 25%, p = 0.03). In addition, OP were more prone of having multiples irAEs compared with YP (p = 0.037). Skin toxicities were more frequent in OP than in YP (p = 0.007) but endocrine toxicities were less frequent in OP than in YP (p = 0.044). This higher level of irAEs seems to be responsible for a higher rate of treatment discontinuation in OP (p = 0.2). There was no statistical difference in median time to toxicity, exposure to steroids or survival between the two groups., Conclusion: Although anti-PD-(L)1 immunotherapies remain an acceptable treatment option for older patients, prescribers should be aware that irAEs are more frequent in the elderly. Further translational studies are warranted to better understand the relationship between aging and irAEs., (Copyright © 2020. Published by Elsevier Ltd.)

Aims: Antibacterial activities of phenylpropenes (PPs) (eugenol, isoeugenol, estragole and trans-anethole) and hydroxycinnamic acids (HCAs) (p-coumaric, caffeic and ferulic acids) were assessed against Escherichia coli and Staphylococcus epidermidis. Effect of cyclodextrin and liposome encapsulation on the PPs activity was also evaluated., Methods and Results: All PPs inhibited the bacterial growth in the hundred micromolar range, while HCAs did not, as determined by broth macrodilution. Anethole and estragole showed a higher efficiency than eugenol and isoeugenol, and E. coli was more susceptible than S. epidermidis. Hydroxypropyl-β-cyclodextrin/PP complexes and anethole-loaded Lipoid S100-liposomes were prepared by freeze-drying and ethanol injection respectively. Both formulations were substantially less active than free PPs. For instance, E. coli growth inhibition was about 14% for all HP-β-CD/PP complexes evaluated at MIC 50 values of free PPs (P < 0·05), and about 12% for liposomal anethole evaluated at minimal bactericidal concentration value of free anethole (P < 0·05)., Conclusions: Hydrophobicity appears to be crucial for PPs antibacterial activity. Encapsulation in cyclodextrin and liposome seems to retain the PPs preventing their interaction with bacteria., Significance and Impact of the Study: This study highlights the structural features of simple phenylpropanoids related to their antibacterial activity. The limitations of conventional encapsulation systems on the activity of PPs should be considered in future applications., (© 2019 The Society for Applied Microbiology.)

Although a quarter of cervical cancers occur after the age of 65 years, there is no treatment consensus for these patients. The aim of this work was to survey how physicians treat patients with advanced cervical cancer, focusing on treatment adjustments according to age and frailty status. Specialists were invited to an online survey. Data collected included information on respondent and treatment strategy in four cases (FIGO IIb, FIGO IVa, FIGO IVb, metastatic recurrence) with three age scenarios (45-year-old, 75-year-old and fit, 75-year-old and unfit). We received 237 responses of which 117 were fully completed. Thirty-four percent of respondents reported they had available access to a geriatric team and 25% used a frailty screening tool in routine. Therapeutic strategies did not differ between young and old fit patients. However, treatment modalities and intensity were different for old and unfit patients. Physicians answered that they would treat old fit patients as their younger counterparts but would reduce treatment intensity for old unfit patients. However, even if they were willing to adapt their treatment strategy based on frailty status, most of them do not use the tools that would allow distinguishing "fit" and "unfit" older patients, leaving room for improving accurate geriatric evaluation.

Caffeic acid is a natural phenylpropanoid that exhibits various health benefits. However, it suffers from a poor aqueous solubility limiting its application. This drawback could be overcome by complexation in cyclodextrins (CD) or cosolvency. Herein, we investigated, for the first time, the combined effect of CD and ethanol as cosolvent on complexation, solubilization and antioxidant activity of caffeic acid. Results showed that CD, ethanol and their combined use enhanced the solubility of this phenylpropanoid. However, the presence of ethanol affects the formation of inclusion complexes as lower formation constants (K f ) and complexation efficiencies (CE) were obtained while increasing the ethanol percentage (0-45% v/v). No inclusion complex could be observed at 45% v/v ethanol. These results were confirmed by 2D DOSY and 2D ROESY NMR experiments. Furthermore, the antioxidant activity of caffeic acid in the combined system was enhanced consequent to its increased solubility., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Cancer immunotherapy is aimed at stimulating tumor-specific cytotoxic T lymphocytes and their subsequent trafficking so that they may reach, and persist in, the tumor microenvironment, recognizing and eliminating malignant target cells. Thus, characterization of the phenotype and effector functions of CD8 + T lymphocytes infiltrating human solid tumors is essential for better understanding and manipulating the local antitumor immune response, and for defining their contribution to the success of current cancer immunotherapy approaches. Accumulating evidence indicates that a substantial subpopulation of CD3 + CD8 + tumor-infiltrating lymphocytes are tissue resident memory T (T RM ) cells, and is emerging as an activated tumor-specific T-cell subset. These T RM cells accumulate in various human cancer tissues, including non-small-cell lung carcinoma (NSCLC), ovarian and breast cancers, and are defined by expression of CD103 [α E (CD103)β 7 ] and/or CD49a [α1(CD49a)β1] integrins, along with C-type lectin CD69, which most likely contribute to their residency characteristic. CD103 binds to the epithelial cell marker E-cadherin, thereby promoting retention of T RM cells in epithelial tumor islets and maturation of cytotoxic immune synapse with specific cancer cells, resulting in T-cell receptor (TCR)-dependent target cell killing. Moreover, CD103 integrin triggers bidirectional signaling events that cooperate with TCR signals to enable T-cell migration and optimal cytokine production. Remarkably, T RM cells infiltrating human NSCLC tumors also express inhibitory receptors such as programmed cell death-1, the neutralization of which, with blocking antibodies, enhances CD103-dependent TCR-mediated cytotoxicity toward autologous cancer cells. Thus, accumulation of T RM cells at the tumor site explains the more favorable clinical outcome, and might be associated with the success of immune checkpoint blockade in a fraction of cancer patients.

Cyclodextrins (CDs) are a family of cyclic oligosaccharides that constitute one of the most widely used molecular hosts in supramolecular chemistry. Encapsulation in the hydrophobic cavity of CDs positively affects the physical and chemical characteristics of the guests upon the formation of inclusion complexes. Such a property is interestingly employed to retain volatile guests and reduce their volatility. Within this scope, the starting crucial point for a suitable and careful characterization of an inclusion complex is to assess the value of the formation constant (K f ), also called stability or binding constant. This task requires the application of the appropriate analytical method and technique. Thus, the aim of the present paper is to give a general overview of the main analytical tools used for the determination of K f values for CD/volatile inclusion complexes. This review emphasizes on the advantages, inconvenients and limits of each applied method. A special attention is also dedicated to the improvement of the current methods and to the development of new techniques. Further, the applicability of each technique is illustrated by a summary of data obtained from the literature.

Nootkatone (NO) is a sesquiterpenoid volatile flavor, used in foods, cosmetics and pharmaceuticals, possessing also insect repellent activity. Its application is limited because of its low aqueous solubility and stability; this could be resolved by encapsulation in cyclodextrins (CDs). This study evaluated the encapsulation of NO by CDs using phase solubility studies, Isothermal Titration Calorimetry, Nuclear Magnetic Resonance spectroscopy and molecular modeling. Solid CD/NO inclusion complex was prepared and characterized for encapsulation efficiency and loading capacity using UV-Visible. Thermal properties were investigated by thermogravimetric-differential thermal analysis and release studies were performed using multiple headspace extraction. Formation constants (K f ) proved the formation of stable inclusion complexes. NO aqueous solubility, photo- and thermal stability were enhanced and the release could be insured from solid complex in aqueous solution. This suggests that CDs are promising carrier to improve NO properties and, consequently, to enlarge its use in foods, cosmetics, pharmaceuticals and agrochemicals preparations., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This study aimed to evaluate the effect of the preparation method, temperature and humidity on the release of aroma from β-cyclodextrin (β-CD) solid inclusion complexes (IC). Therefore β-CD/trans-anethole (β-CD/AN) IC were prepared by freeze-drying (FD) and co-precipitation coupled to FD (Cop-FD). Release experiments were performed at various temperatures and relative humidities (RH). Multiple headspace extraction-gas chromatography (MHE) was used to determine the loading capacity (LC) and encapsulation efficiency (EE%) and perform release studies. Results underlined that the quantification of encapsulated AN by MHE requires the IC dissolution. The release of AN was accelerated by increases in RH and temperature. However, it was quite negligible below 75% RH. The release behavior of AN was well simulated by Avrami's equation. Cop-FD IC retained more efficiently AN and the release depended on the preparation method and treatment conditions. Thus, the preparation method could be chosen based on the application., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Formation of inclusion complexes with cyclodextrins (CDs) is known to enhance guest solubility in aqueous medium. Different techniques allow determining the evolution in solubility of individual guest compounds. However, examination of mixtures solubility encapsulated in CDs is still a challenge. This is mainly related to the difference in the response of mixture components to the applied technique or to the fact that most of the conventional methods examine the signal of an individual constituent of the mixture. Thus, applying current techniques may not reflect the behavior of the whole mixture. Here, we used for the first time Total Organic Carbon (TOC) analysis to explore and assess the efficiency of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to enhance the solubility of natural complex mixtures such as essential oils (EOs). Phase solubility studies were performed for eleven EOs with HP-β-CD. The TOC method has provided good validation parameters for linearity, precision and accuracy. For further validation of the method, phase solubility studies were performed with HP-β-CD for eugenol, as a model EO component. The eugenol solubility was determined by UV-Visible and TOC analyses in order to compare the results. Data obtained from both methods were similar (p < 0.05), thereby proving the effectiveness of the developed TOC method. Finally, the phase solubility diagrams of EOs showed that the solubilizing potential of CD increased proportionally with the decrease in EO intrinsic solubility. Results proved that TOC could be successfully applied to investigate CD/guest inclusion complexes and is expected to have a broad range of applications in the field of mixtures encapsulation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Effects of the encapsulation in cyclodextrins (CDs) on the solubility, photostability and antifungal activities of some phenylpropanoids (PPs) were investigated. Solubility experiments were carried out to evaluate the effect of CDs on PPs aqueous solubility. Loading capacities and encapsulation efficiencies of freeze-dried inclusion complexes were determined. Moreover, photostability assays for both inclusion complexes in solution and solid state were performed. Finally, two of the most widespread phytopathogenic fungi, Fusarium oxysporum and Botrytis cinerea, were chosen to examine the antifungal activity of free and encapsulated PPs. Results showed that encapsulation in CDs significantly increased the solubility and photostability of studied PPs (by 2 to 17-fold and 2 to 44-fold, respectively). Free PPs revealed remarkable antifungal properties with isoeugenol showing the lowest half-maximal inhibitory concentration (IC50) values of mycelium growth and spore germination inhibition. Encapsulated PPs, despite their reduced antifungal activity, could be helpful to solve drawbacks such as solubility and stability., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Carvacrol and thymol have been widely studied for their ability to control food spoilage and to extend shelf-life of food products due to their antimicrobial and antioxidant activities. However, they suffer from poor aqueous solubility and pronounced flavoring ability that limit their application in food systems. These drawbacks could be surpassed by encapsulation in cyclodextrins (CDs). Applications of their inclusion complexes with CDs were reported without investigating the inclusion phenomenon in deep. In this study, inclusion complexes were characterized in terms of formation constants (K f), complexation efficiency (CE), CD:guest molar ratio and increase in bulk formulation by using an UV-visible competitive method, phase solubility studies as well as (1)H and DOSY (1)H NMR titration experiments. For the first time, a new algorithmic treatment that combines the chemical shifts and diffusion coefficients variations for all guest protons was applied to calculate K f. The position of the hydroxy group in carvacrol and thymol did not affect the stoichiometry of the inclusion complexes but led to a different binding stability with CDs. 2D ROESY NMR experiments were also performed to prove the encapsulation and illustrate the stable 3D conformation of the inclusion complexes. The structural investigation was accomplished with molecular modeling studies. Finally, the radical scavenging activity of carvacrol and thymol was evaluated by the ABTS radical scavenging assay. An improvement of this activity was observed upon encapsulation. Taken together, these results evidence that the encapsulation in CDs could be valuable for applications of carvacrol and thymol in food.

Essential oils (EOs) are gaining great interest as alternatives for harmful synthetic food preservatives. Due to their volatile nature, they could be applied in food packaging to improve food quality and extend shelf-life. To provide long-term effects of EOs by increasing their retention and ensuring controlled release of their components, they could be encapsulated in cyclodextrins (CDs). Herein, the ability of six CDs to retain nine EOs and to bind their individual components was investigated. Retention capacities and binding abilities of CDs were assessed by static headspace-gas chromatography (SH-GC) using a new validated "rapid method". The ability of CDs to generate controlled release systems was examined by multiple headspace extraction (MHE). Finally, radical scavenging activity of free and encapsulated EOs was evaluated. The highest retention capacity toward the studied EOs was obtained for β-CD and its derivatives (69-78%). Also, β-CD and its derivatives showed, with one exception, the highest Kf values for all the studied guests. In addition, encapsulation in CDs reduced the releasing rate of EO components (from 1.43 to 2.43-fold for β-CD/Satureja montana EO used as a model). Furthermore, the inclusion complexes showed higher ABTS(+) scavenging capacity than the free EOs. Results confirmed the usefulness of CDs as encapsulant for EOs and should encourage their application in food and as part of active packaging systems., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Inclusion complexes of estragole (ES) as pure compound and as main component of basil and tarragon essential oils (EOs) with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), randomly methylated-β-cyclodextrin (RAMEB), a low methylated-β-cyclodextrin (CRYSMEB) and γ-cyclodextrin (γ-CD) were characterized. Formation constants (Kf) of the complexes were determined in aqueous solution by nonlinear regression analysis using static headspace gas chromatography (SH-GC) and UV-visible spectroscopy. Solid inclusion complexes were prepared by the freeze-drying method for different CD:ES molar ratios and were characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). Inclusion complexes formation allowed the controlled release of ES. Moreover, increased DPPH radical scavenging activity and photostability of ES and ES containing EOs (ESEOs) were observed in the presence of CDs. These findings suggest that encapsulation with CDs could be an efficient tool to improve the use of ES and ESEOs in aromatherapy, cosmetic and food fields., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Inclusion complexes of trans-anethole (AN) with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), randomly methylated-β-cyclodextrin (RAMEB) and a low methylated-β-cyclodextrin (CRYSMEB) were investigated in aqueous solution by static headspace gas chromatography (SH-GC), phase solubility study, UV-Visible, (1)H NMR and (2D) ROESY NMR spectroscopies. The obtained results indicated the formation of 1:1 inclusion complex for all the studied CDs. Water solubility of AN was significantly improved upon complexation with CDs as demonstrated by phase solubility and retention studies. Solid inclusion complexes were prepared by the freeze-drying method and the encapsulation of AN was confirmed by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies. Moreover, the degradation of AN, induced by UVC irradiation, was markedly reduced by the formation of CD inclusion complexes. Results showed that encapsulation in CDs was an efficient way to increase solubility and stability of AN, thereby making it valuable for food or pharmaceutical applications., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The complexation abilities of five cyclodextrins (CDs) with seven phenylpropanoids (PPs) were evaluated by UV-visible spectroscopy, phase solubility studies and molecular modeling. Formation constants (K f), complexation efficiency (CE), PP:CD molar ratio, increase in formulation bulk and complexation energy were assessed. All complexes exhibited a 1:1 stoichiometry but their stability was influenced by the nature and the position of the phenyl ring substituents. A relationship between the intrinsic solubility of guests (S 0) and the solubilizing potential of CD was proposed. Molecular modeling was used to investigate the complementarities between host and guest. Finally, the antioxidant activity of encapsulated PPs was evaluated by scavenging of the stable DPPH radical.

Cyanide poisoning has existed for centuries. In most cases, cyanide is combined with other toxic substances; for example with carbon monoxide in fire smoke. Cases of pure cyanide poisoning are rare, and usually due to accidental exposure. Their treatment is based on oxygenation and the infusion of hydroxocobalamin. The seriousness of this type of poisoning calls for a rapid and specific response, which demonstrates the usefulness of non-hospital based medical treatment. The authors report here the case of a man who was the victim of occupational poisoning with sodium cyanide and who was treated at the workplace by fire-fighters and the Service Mobile d'Urgence et Reanimation emergency ambulance service.