Qualitative research on cancer patients' survivor-identity and lived experiences in low- and middle-income countries is scarce. Our study aimed at exploring the concept and experience of survivorship ...for Mexicans living with breast, cervical, and prostate cancer.
We conducted a qualitative study in Mexico City, Morelos, Nuevo León, and Puebla. The participants were breast, cervical, and prostate cancer patients ≥18 years of age with completed primary cancer treatment. Data were collected via in-depth interviews and analyzed using an inductive thematic approach.
The study included 22 participants with a history of breast, 20 cervical, and 18 prostate cancer. Participants accepted the term "cancer survivor" as a literal interpretation of being alive, medical confirmation of treatment completion, or achievement of a clinical result possibly indicative of cure. The majority of respondents perceived that the future is out of their control and under God's will. They linked cure to divine intervention and did not demonstrate the sense of empowerment that is often associated with the survivorship term. The principal themes of their narratives encompass: 1) adverse physical and sexual experiences; 2) emotional problems; 3) cancer-related stigma; 4) challenges to obtaining health-related information; 5) financial hardship; and 6) experience of strengthening family ties in order to provide them with support. In addition, women with breast cancer reported distress caused by changes in body image and positive experience with support groups.
In Mexico, cancer patients report complex survivorship experiences that demand post-treatment follow-up and support. There is the need to implement comprehensive, culturally-relevant survivorship programs focused on emotional, informational, and in-kind support and empowerment of cancer patients.
Purpose
Caspase-associated recruitment domain-9 (CARD9) deficiency is an inborn error of immunity that typically predisposes otherwise healthy patients to single fungal infections and the occurrence ...of multiple invasive fungal infections is rare. It has been described as the first known condition that predisposes to extrapulmonary
Aspergillus
infection with preserved lungs. We present a patient that expands the clinical variability of CARD9 deficiency.
Materials and methods
Genetic analysis was performed by Sanger sequencing. Neutrophils and mononuclear phagocyte response to fungal stimulation were evaluated through luminol-enhanced chemiluminescence and whole blood production of the proinflammatory mediator interleukin (IL)-6, respectively.
Results
We report a 56-year-old Argentinean woman, whose invasive
Exophiala spinifera
infection at the age of 32 years was unexplained and reported in year 2004. At the age of 49 years, she presented with chronic pulmonary disease due to
Aspergillus nomius.
After partial improvement following treatment with caspofungin and posaconazole, right pulmonary bilobectomy was performed. Despite administration of multiple courses of antifungals, sustained clinical remission could not be achieved. We recently found that the patient’s blood showed an impaired production of IL-6 when stimulated with zymosan. We also found that she is homozygous for a previously reported
CARD9
loss-of-function mutation (Q289*).
Conclusions
This is the first report of a patient with inherited CARD9 deficiency and chronic invasive pulmonary aspergillosis (IPA) due to
A. nomius
. Inherited CARD9 deficiency should be considered in otherwise healthy children and adults with one or more invasive fungal diseases.
This paper aims at investigating the failure response of expanded metal meshes subject to transversal impact. Firstly, the study is performed through explicit nonlinear finite element analysis, in ...which a numerical model is developed to determine the impact performance and failure mode of expanded metal meshes. Thereafter, the effect of expanded metal cell geometries, impact mass and velocity on the structural response of the meshes is analyzed. Then the perforation resistance of the impacted meshes is assessed and analyzed by means of vulnerability curves for various expanded metal geometries subject to transversal impact. The extent of damage in the meshes is also evaluated, and the maximum displacements achieved in each impact scenario is quantified. At the end, it is demonstrated that the perforation performance of the meshes depends on the expanded metal cell dimensions expressed as a combination of the strand cross-section and major axis length. Finally, the results also show the feasibility of using expanded metal meshes to protect structures impacted by flying debris.
Los tumores cutáneos presentan una alta prevalencia en dermatología en el mundo, siendo los benignos más frecuentes que los malignos; sin embargo, estos últimos son más estudiados debido a su ...morbimortalidad. El objetivo principal de este estudio fue conocer los principales diagnósticos y técnicas quirúrgicas correspondientes desarrolladas en el Centro de Tratamiento de Enfermedades de la Piel (CETEP) entre 1996 y 2019, evaluando aspectos clínicos y demográficos. Se realizó un estudio retrospectivo y observacional que incluyó todo paciente con lesión cutánea y posterior resolución quirúrgica de la misma. En la muestra analizada (N 6.659) hubo un predominio del sexo femenino (68%) y la media de edad fue 53 ± 21 años. Los pacientes residían mayoritariamente en Montevideo (58%). Los tumores benignos fueron los más frecuentes (41%), seguidos de los malignos (28%), dentro de éstos: carcinoma basocelular (CBC) 66%, carcinoma espinocelular (CEC) 21% y melanoma (MM) 5%. Las técnicas quirúrgicas realizadas fueron cirugías convencionales (57%), principalmente losange (93%), seguidas de procedimientos de cirugía dermatológica (42%), predominando biopsias (52%) y afeitado con electrocoagulación (23%). Se destaca que el CETEP resolvió un número mayor de pacientes de centros externos que del propio Centro Hospitalario Pereira Rossell (CHPR): 59% no CHPR vs 41% CHPR. En conclusión, este trabajo proporcionó información nacional sobre la epidemiología de distintos tumores cutáneos, así como las técnicas quirúrgicas más utilizadas en su resolución. Además, estableció la importancia de la cirugía dermatológica y la capacidad del CETEP en dar respuesta a pacientes propios tanto como referenciados desde otros centros del sistema público.
Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.
We performed an ...international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.
Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval CI, 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.
We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).
We evaluated a patient with disseminated Mycobacterium tuberculosis and Mycobacterium chelonae infection, of which he died. He also developed autoimmune (type I) diabetes and primary hypothyroidism. ...His serum contained a high titer of immunoglobulin G autoantibody to interferon-γ (IFN-γ) capable of blocking in vitro responses to this cytokine by peripheral blood mononuclear cells from normal donors. These results suggest that autoantibodies to IFN-γ can induce susceptibility to disseminated mycobacterial infection, which may be refractory to chemotherapy.
Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin ...(IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon IFN-gamma, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1beta, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-beta, tumor necrosis factor alpha, or transforming growth factor beta). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.
Abstract
Background
Lung metastasis is the most adverse clinical factor and remains the leading cause of osteosarcoma-related death. Deciphering the mechanisms driving metastatic spread is crucial ...for finding open therapeutic windows for successful organ-specific interventions that may halt or prevent lung metastasis.
Methods
We employed a mouse premetastatic lung-based multi-omics integrative approach combined with clinical features to uncover the specific changes that precede lung metastasis formation and identify novel molecular targets and biomarker of clinical utility that enable the design of novel therapeutic strategies.
Results
We found that osteosarcoma-bearing mice or those preconditioned with the osteosarcoma cell secretome harbour profound lung structural alterations with airway damage, inflammation, neutrophil infiltration, and extracellular matrix remodelling with increased deposition of fibronectin and collagens by resident stromal activated fibroblasts, favouring the adhesion of disseminated tumour cells. Systemic-induced microenvironmental changes, supported by transcriptomic and histological data, promoted and accelerated lung metastasis formation. Comparative proteome profiling of the cell secretome and mouse plasma identified a large number of proteins involved in extracellular-matrix organization, cell-matrix adhesion, neutrophil degranulation, and cytokine-mediated signalling, consistent with the observed lung microenvironmental changes. Moreover, we identified EFEMP1, an extracellular matrix glycoprotein exclusively secreted by metastatic cells, in the plasma of mice bearing a primary tumour and in biopsy specimens from osteosarcoma patients with poorer overall survival. Depletion of EFEMP1 from the secretome prevents the formation of lung metastasis.
Conclusions
Integration of our data uncovers neutrophil infiltration and the functional contribution of stromal-activated fibroblasts in ECM remodelling for tumour cell attachment as early pro-metastatic events, which may hold therapeutic potential in preventing or slowing the metastatic spread. Moreover, we identified EFEMP1, a secreted glycoprotein, as a metastatic driver and a potential candidate prognostic biomarker for lung metastasis in osteosarcoma patients.
Graphical abstract
Osteosarcoma-derived secreted factors systemically reprogrammed the lung microenvironment and fostered a growth-permissive niche for incoming disseminated cells to survive and outgrow into overt metastasis.
Daily administration of osteosarcoma cell secretome mimics the systemic release of tumour-secreted factors of a growing tumour in mice during PMN formation;
Transcriptomic and histological analysis of premetastatic lungs revealed inflammatory-induced stromal fibroblast activation, neutrophil infiltration, and ECM remodelling as early onset pro-metastatic events;
Proteome profiling identified EFEMP1, an extracellular secreted glycoprotein, as a potential predictive biomarker for lung metastasis and poor prognosis in osteosarcoma patients.
Osteosarcoma patients with EFEMP1 expressing biopsies have a poorer overall survival.
Background/aims
To evaluate the efficacy, safety and durability of intravitreal faricimab in patients with neovascular age-related macular degeneration (nAMD) with unsatisfactory response to ...traditional anti-vascular endothelial growth factor (anti-VEGF) agents.
Methods
Single-centre, prospective cohort study of all consecutive patients with nAMD who were switched to intravitreal faricimab from intravitreal ranibizumab or aflibercept, due to unsatisfactory treatment response (maximal fluid-free interval ≤ 8 weeks). Intravitreal faricimab was administered with a loading dose of four 4-weekly injections, followed by an 8-week extension. A treat and extend (T&E) regime was adopted thereafter. Primary outcome was the difference between the maximal fluid-free interval achieved with faricimab, and the one achieved before the switch. Morpho-functional outcomes were also assessed. Secondary outcome was accordance with clinical management when applying faricimab pivotal trial criteria versus our real-world T&E protocol, measured as a proportion.
Results
Twenty-six eyes of 26 patients with a median age of 82 years (range 77–85) were included. Patients were followed for 30.2 weeks (range 26.3–33.1). Maximal fluid-free interval after switch to faricimab (Mdn = 6.0 weeks; IQR = 4–8) was longer than the maximum interval before the switch (Mdn = 4.0 weeks; IQR = 4–4),
p
< 0.001. Comparing real-world T&E protocol with pivotal trial criteria, 8 (30.8%) eyes received the same clinical management while 18 (69.2%) eyes were kept at a shorter interval when following our T&E protocol. No serious adverse events were recorded.
Conclusions
Faricimab appears to increase the fluid-free interval and allow extension of dosing interval in patients with nAMD poorly responsive to traditional anti-VEGF drugs.
This paper describes the standard of care for patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) and the therapeutic recommendations developed by the European paediatric Soft tissue ...sarcoma Study Group (EpSSG). NRSTS form a very mixed group of mesenchymal extraskeletal malignancies. Their rarity, heterogeneity, and aggressiveness make the management of children and adolescents with these tumors complex and challenging. The overall cure rate for patients with NRSTS is around 70%, but survival depends on several prognostic variables, such as histotype and tumor grade, extent of disease and stage, tumor size, and tumor site. While surgery remains the mainstay of treatment for most of these tumors, a multimodal therapeutic approach including radiotherapy and chemotherapy is required in many cases. The EpSSG NRSTS 2005 study was the first prospective protocol tailored specifically to NRSTS. Together with the ARST0332 study developed by the North-American Soft Tissue Sarcoma Committee of the Children's Oncology Group (COG), the EpSSG NRSTS 2005 study currently represents the benchmark for these tumors, establishing risk-adapted standards of care. The EpSSG has developed common treatment recommendations for the large group of adult-type NRSTS (including synovial sarcoma), and specific treatment recommendations for other particular adult-type histologies (ie, alveolar soft-part sarcoma, clear cell sarcoma and dermatofibrosarcoma protuberans); other highly malignant tumors with a biology and clinical behavior differing from those of adult-type NRSTS (ie, rhabdoid tumors and desmoplastic small round cell tumor); and soft tissue tumors of intermediate malignancy (ie desmoid-type fibromatosis, inflammatory myofibroblastic tumors, and infantile fibrosarcoma). New effective drugs are needed for patients whose NRSTS carries the worst prognosis, ie, those with unresectable tumors, metastases at diagnosis, or relapsing disease. Progress in this area relies on our ability to develop international integrated prospective collaborations, both within existing pediatric oncology networks and, importantly, between the communities of specialists treating pediatric and adult sarcoma.
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