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Medical oncology is a rapidly evolving field, with new medications being discovered yearly, contributing to increased survival rates. However, accessing drugs in a timely manner can be challenging. In Quebec, Canada, a physician can prescribe an unlisted anticancer treatment through a regulated pathway under exceptional circumstances. We conducted a quality improvement study describing the outcomes of incurable cancer patients receiving unlisted anticancer therapy at the Jewish General Hospital between 2018 and 2019. Though our study did not include a comparator arm, unlisted anticancer therapies were associated with interesting median progression-free survival (11 months) and overall survival (25 months). Moreover, a large proportion of treatments, 44%, were subsequently reimbursed in the province of Quebec. Given the delay in anticancer drug reimbursement, this pathway is essential for timely access to oncology drugs. Such ‘special access’ programs will likely become increasingly important as precision medicine becomes the standard of practice.

Abstract Circulating free tumor DNA (ctDNA) analysis is gaining popularity in precision oncology, particularly in metastatic breast cancer, as it provides non-invasive, real-time tumor information to complement tissue biopsies, allowing for tailored treatment strategies and improved patient selection in clinical trials. Its use in early breast cancer has been limited so far, due to the relatively low sensitivity of available techniques in a setting characterized by lower levels of ctDNA shedding. However, advances in sequencing and bioinformatics, as well as the use of methylome profiles, have led to an increasing interest in the application of ctDNA analysis in early breast cancer, from screening to curative treatment evaluation and minimal residual disease (MRD) detection. With multiple prospective clinical trials in this setting, ctDNA evaluation may become useful in clinical practice. This article reviews the data regarding the analytical validity of the currently available tests for ctDNA detection and the clinical potential of ctDNA analysis in early breast cancer.

Background: We describe an epidemiological investigation of a SARS-CoV-2-XBB.1 outbreak among healthcare workers (HCWs) returning from a 5-days educational tour abroad. Methods: We prospectively followed participants for symptoms and sampled blood for neutralization assays of four SARS-CoV-2 variants (wild type, XBB, EG.5.1, and BA.2.86) at 1, 3, and 6 months after their return. When available, samples from the 3 months preceding the outbreak were also tested. We compared geometric mean titers (GMT) of neutralizing antibodies of infected versus uninfected HCWs and febrile versus afebrile infected HCWs. Results: Nineteen (10%) of 181 HCWs were infected, all had mild COVID-19, 90% (17/19) had symptoms, and 16% (3/19) reported fever. Infected individuals tended to have lower pre-exposure XBB-neutralizing antibody titers (GMT of 32 versus 107 ID50, P = 0.248). Neutralization against XBB and newer subvariants peaked at 3 months and was higher among infected individuals (GMT 702 versus 156 [P < 0.001], 558 versus 163 [P = 0.001], and 558 vs. 182 [P = 0.002], ID50 for XBB, EG.5.1., and BA.2.86, respectively). By six months, these differences were no longer observed. Fever was positively associated with XBB neutralization (GMT 3474 versus 485, ID50 P = 0.005). Conclusions: Recently infected individuals are protected from reinfection with newer subvariants. However, protection is likely short lived.

Abstract This study aims to detect residual thermal anomalies along the path of a hotspot beneath the continental lithosphere using gradiometry data. We calculate perturbations in gravity vectors and gradients by employing a simple thermal anomaly model. The results highlight that the horizontal components of Bouguer gravity gradients, sensitive to source structure and elongation, exhibit substantial magnitudes, exceeding current detection levels. To improve signals from sources of different sizes and orientations, we apply a filtering approach involving wavelet transforms and rotated local frames. We also assess the impact of lateral crustal variations on the gravity field by introducing random density anomalies and a seismic crustal model, testing the method's ability to distinguish between these anomalies and thermal sources. Using Gravity field and steady‐state Ocean Circulation Explorer satellite data, we generated scale‐orientation diagrams aiming to identify signals aligned with the direction of plate movement and with a spatial scale of a few hundred kilometers (scale of the plumes). Maps of filtered Bouguer gravity gradients aligned with hotspot trajectories are generated for all continental hot plumes, with the position and the age of the intraplate volcanism to support the interpretation. While we do not show a clear signal in regions that are too tectonically complex or with lateral variations in the crust or at the lithospheric boundary correlated with the hotspot trace, we found observed signals with expected sign and amplitude over Hoggar, Tibesti, Darfour and Cameroon tracks in Africa and over Iceland and Jan Mayen in Greenland. However, determining corresponding mass source depths remains a complex task.

Iron and manganese are poorly soluble elements in oxic and alkaline solutions, whereas they are much more soluble under anoxic conditions. As a result, the formation of authigenic mineral phases rich in Fe and/or Mn has traditionally been viewed as diagnostic of global or local anoxic conditions. Here we reveal that some specific cyanobacteria of very small size (< 2 µm, i.e., picocyanobacteria) can biomineralize abundant, authigenic Fe(III)-, Mn(IV)- and Si-rich amorphous phases under oxic conditions in an alkaline lake in Mexico. The resulting biominerals cluster as small globules arranged as rings around the division septum of cyanobacterial cells. These rings are enveloped within an organic, likely polysaccharidic envelope and are partially preserved, at least morphologically, upon sedimentation. Based on their 16S rDNA sequence, these cyanobacteria were affiliated with the Synechococcales order. The high Fe and Mn enrichment of the biominerals questions the systematic inference of anoxic conditions based on their detection. Moreover, this process scavenges iron from the water column, an overlooked biological contribution to the Fe cycle. Finally, it reveals a new case of controlled biomineralization of Si-rich phases by bacteria.

Background: Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM. Methods: We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint. Results: 7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine. Conclusions: The results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies.

Summary: Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to infant neurodevelopmental disabilities. An improved knowledge of correlates of protection against cCMV is needed to guide prevention strategies. Here, we employ an ex vivo model of human CMV (HCMV) infection in decidual tissues of women with and without preconception immunity against CMV, recapitulating nonprimary vs. primary infection at the authentic maternofetal transmission site. We show that decidual tissues of women with preconception immunity against CMV exhibit intrinsic resistance to HCMV, mounting a rapid activation of tissue-resident memory CD8+ and CD4+ T cells upon HCMV reinfection. We further reveal the role of HCMV-specific decidual-tissue-resident CD8+ T cells in local protection against nonprimary HCMV infection. The findings could inform the development of a vaccine against cCMV and provide insights for further studies of the integrity of immune defense against HCMV and other pathogens at the human maternal-fetal interface.

BackgroundPhase 2 cooperative group meningioma trial assessing the safety and efficacy of risk-adaptive management strategies. This is the initial analysis of the high-risk cohort.Methods and materialsHigh-risk patients were those with a new or recurrent World Health Organization (WHO) grade III meningioma of any resection extent, recurrent WHO grade II of any resection extent, or new WHO grade II after subtotal resection. Patients received intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost technique (60 Gy high dose and 54 Gy low dose in 30 fractions). Three-year progression-free survival (PFS) was the primary endpoint. Adverse events (AEs) were scored per NCI Common Terminology Criteria for Adverse Events version 3.ResultsOf 57 enrolled patients, 53 received protocol treatment. Median follow-up was 4.0 years (4.8 years for living patients). Two patients withdrew without progression before year 3; for the remaining 51 patients, 3-year PFS was 58.8%. Among all 53 protocol-treated patients, 3-year PFS was 59.2%. Three-year local control was 68.9%, and overall survival was 78.6%. Of 51 patients, 1 patient (1.9%) experienced a late grade-5 necrosis-related AE. All other acute (23 of 53 patients) and late (21 of 51 patients) AEs were grades 1 to 3.ConclusionsPatients with high-risk meningioma treated with IMRT (60 Gy/30) experienced 3-year PFS of 58.8%. Combined acute and late AEs were limited to grades 1 to 3, except for a single necrosis-related grade 5 event. These results support postoperative IMRT for high-risk meningioma and invite ongoing investigations to improve outcomes further.

Patients with oligometastatic breast cancer (BC) are candidates of choice for metastasis-directed therapy (MDT). This paper summarizes the opinions of an expert committee about the management of oligometastatic BC. The experts could complete the questionnaire from 13 September 2021, to 10 October 2021, followed by a discussion. The experts were physicians working in the Province of Quebec (Canada) and specialized in BC care, including surgical oncologists, medical oncologists, and radiation oncologists. The experts provided their opinions about the context of the disease and therapeutic approach, local and systemic therapies, and the prognosis of oligometastatic BC. In addition to the expert panel’s opinions about the management of oligometastatic disease per se, the experts stated that a prospective data registry should be implemented to collect data about oligometastatic BC to improve knowledge about oligometastatic BC and implement data-driven MDT. These data could also allow for the design of treatment algorithms. In conclusion, this paper presents the expert panel’s opinions about the management of oligometastatic BC and highlights the needs to be met to improve the care of this condition.

Medical oncology is a rapidly evolving field, with new medications being discovered yearly, contributing to increased survival rates. However, accessing drugs in a timely manner can be challenging. In Quebec, Canada, a physician can prescribe an unlisted anticancer treatment through a regulated pathway under exceptional circumstances. We conducted a quality improvement study describing the outcomes of incurable cancer patients receiving unlisted anticancer therapy at the Jewish General Hospital between 2018 and 2019. Though our study did not include a comparator arm, unlisted anticancer therapies were associated with interesting median progression-free survival (11 months) and overall survival (25 months). Moreover, a large proportion of treatments, 44%, were subsequently reimbursed in the province of Quebec. Given the delay in anticancer drug reimbursement, this pathway is essential for timely access to oncology drugs. Such 'special access' programs will likely become increasingly important as precision medicine becomes the standard of practice. [ABSTRACT FROM AUTHOR]

Purpose: Dural-based metastases (DBM) are present in 4% of all patients diagnosed with metastatic cancer. DBM most commonly arise from primary cancers of the lung, breast, and prostate. While diagnostic challenges are relatively well studied, the epidemiology, common intracranial locations, and therapeutic outcomes of DBM remain poorly understood. Our current study aims to define the epidemiological characteristics of patients presenting with DBM, the most common locations of metastasis within the dura, and clinical outcomes after surgery and radiation therapy. Methods: Patients presenting to the Montreal Neurological Institute for intracranial metastasis between the years 2010 and 2016 were reviewed, and patients with DBM were identified based on radiological characteristics. Data were extracted from patient charts and MRIs. Results: A total of 46 patients met inclusion criteria and were included in the study. The mean age at DBM diagnosis was 57 years old. Lung cancer was the most common origin (57%), while breast cancer was the second most common (22%). DBM were more likely to present in patients with active systemic disease (63%) and were found within 1 cm of a major venous sinus in 52% of cases. 87% of patients underwent gross total resection of their tumors. In these patients, adjuvant SRS was associated with a 2-fold increase in mean survival time (p = 0.013). Conclusion: Although DBM are a marker of advanced systemic cancer, surgical resection with adjuvant radiotherapy may play a role in control of intracranial disease and overall patient survival.

O texto abre uma reflexão sobre a importância da arte, dos artistas e principalmente do cinema para conseguir digerir e viver bem nos tempos atuais os quais estamos vivendo em pânico. A arte proporciona a quem faz e a quem recebe diferentes níveis de abstração que nos fazem ampliar a percepção de uma compreensão do mundo. Nada existe até eu fazer um filme sobre o assunto, ou assistir um que me leve à reflexão. Através de uma retrospectiva da relação com o cinema em minha vida, escrevo sobre as razões que me motivaram a flertar, a seguir este caminho e a pensar sobre a vida através de três filmes meus: Amniogênese; O homem que ri e Casa Vazia. The Reflective Character of Cinema: the 7th art as a way of life ABSTRACT The text opens a reflection on the importance of art, artists and especially cinema to be able to digest and live well in the current times we are living in panic. Art provides those who make and those who receive different levels of abstraction that make us broaden the perception of an understanding of the world. Nothing exists until I make a movie about it, or watch one that makes me think. Through a retrospective of the relationship with cinema in my life, I write about the reasons that motivated me to flirt, to follow this path and to think about life through three of my films: Amniogenesis; The Man Who Laughs and an Empty House. Keywords: Cinema. Reflection through art. Art.

Abstract Background COVID‐19 changed the way we practice oncology in multiple ways. Because most cancer patients are comorbid or immunocompromised, we are trying as much as possible to reduce their risk of infection. Marginal just 2 years ago, telemedicine quickly became preeminent with the pandemic to reduce hospital exposure. However, using only virtual visits in oncology patients risk delaying cancer diagnosis or the identification of a complication. Case series We present here four cases where a serious medical problem evident on physical exam was overlooked during a virtual visit. Two of our patients experienced a delay in cancer diagnosis thus putting them at risk of local or distant spread. The two others were established oncology patients where a serious medical complication was missed on a virtual visit. Conclusions Now more than a year into the pandemic, telemedicine has clearly been a useful tool by limiting unnecessary hospital visits. Yet, as our cases illustrate, its use in oncology without clear boundary can undermine the quality of care. Now that effective vaccines are reducing the transmission and the severity of infection, most oncology patients can be evaluated by a real‐time visit.

BACKGROUND Cytomegalovirus (CMV) is the most common intrauterine infection, leading to infant brain damage. Prognostic assessment of CMV-infected fetuses has remained an ongoing challenge in prenatal care, in the absence of established prenatal biomarkers of congenital CMV (cCMV) infection severity. We aimed to identify prognostic biomarkers of cCMV-related fetal brain injury.METHODS We performed global proteome analysis of mid-gestation amniotic fluid samples, comparing amniotic fluid of fetuses with severe cCMV with that of asymptomatic CMV-infected fetuses. The levels of selected differentially excreted proteins were further determined by specific immunoassays.RESULTS Using unbiased proteome analysis in a discovery cohort, we identified amniotic fluid proteins related to inflammation and neurological disease pathways, which demonstrated distinct abundance in fetuses with severe cCMV. Amniotic fluid levels of 2 of these proteins — the immunomodulatory proteins retinoic acid receptor responder 2 (chemerin) and galectin-3–binding protein (Gal-3BP) — were highly predictive of the severity of cCMV in an independent validation cohort, differentiating between fetuses with severe (n = 17) and asymptomatic (n = 26) cCMV, with 100%–93.8% positive predictive value, and 92.9%–92.6% negative predictive value (for chemerin and Gal-3BP, respectively). CONCLUSION Analysis of chemerin and Gal-3BP levels in mid-gestation amniotic fluids could be used in the clinical setting to profoundly improve the prognostic assessment of CMV-infected fetuses.FUNDING Israel Science Foundation (530/18 and IPMP 3432/19); Research Fund – Hadassah Medical Organization.

Three‐dimensional (3D) structure information, now available at the proteome scale, may facilitate the detection of remote evolutionary relationships in protein superfamilies. Here, we illustrate this with the identification of a novel family of protein domains related to the ferredoxin‐like superfold, by combining (i) transitive sequence similarity searches, (ii) clustering approaches, and (iii) the use of AlphaFold2 3D structure models. Domains of this family were initially identified in relation with the intracellular biomineralization of calcium carbonates by Cyanobacteria. They are part of the large heavy‐metal‐associated (HMA) superfamily, departing from the latter by specific sequence and structural features. In particular, most of them share conserved basic amino acids (hence their name CoBaHMA for Conserved Basic residues HMA), forming a positively charged surface, which is likely to interact with anionic partners. CoBaHMA domains are found in diverse modular organizations in bacteria, existing in the form of monodomain proteins or as part of larger proteins, some of which are membrane proteins involved in transport or lipid metabolism. This suggests that the CoBaHMA domains may exert a regulatory function, involving interactions with anionic lipids. This hypothesis might have a particular resonance in the context of the compartmentalization observed for cyanobacterial intracellular calcium carbonates. [ABSTRACT FROM AUTHOR]