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Death Studies Jul 2024Parents experience lasting psychological distress after a child's death from cancer. Limited evidence exists regarding difficult life events, duration of psychosocial...
Parents experience lasting psychological distress after a child's death from cancer. Limited evidence exists regarding difficult life events, duration of psychosocial impacts, and associated risk factors among bereaved parents. Alex's Lemonade Stand Foundation surveyed self-selected, bereaved parents regarding difficult life events and psychosocial wellbeing (life satisfaction, unanswered questions, and missing the care team) through a public, cross-sectional survey. 176 bereaved parents (89% mothers) participated a median of 7 y after their child's death. The most difficult events were family vacations (80%), their child's birthday (80%), and anniversary of their child's death (76%). Only the latter did not improve with time. Greater life satisfaction was associated with male sex (ARR = 1.2, 95% CI:1.1-1.4) and being married/partnered (ARR = 1.2, 95% CI = 1.0-1.3). Having unanswered questions and missing the child's team were associated with annual income <$50,000 (ARR = 1.2, 95% CI:1.1-1.2; ARR = 1.2, 95% CI:1.0-1.3, respectively). Pediatric oncology programs need robust bereavement programs that include prolonged contact with families.
PubMed: 38958178
DOI: 10.1080/07481187.2024.2371074 -
The Cochrane Database of Systematic... Jul 2024This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effectiveness and safety of immune checkpoint inhibitors (ICI) as...
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effectiveness and safety of immune checkpoint inhibitors (ICI) as monotherapy or in combination compared to standard of care for elderly people (≥ 65 years) with non-small cell lung cancer (NSCLC).
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Aged; Immune Checkpoint Inhibitors; Immunotherapy; Systematic Reviews as Topic; Randomized Controlled Trials as Topic; Standard of Care
PubMed: 38958139
DOI: 10.1002/14651858.CD014907.pub2 -
Clinical Chemistry Jul 2024Liquid biopsies are emerging as valuable clinical biomarkers for cancer monitoring. Although International Organization for Standards (ISO) and Technical Specifications...
BACKGROUND
Liquid biopsies are emerging as valuable clinical biomarkers for cancer monitoring. Although International Organization for Standards (ISO) and Technical Specifications from the European Committee for Standardization (CEN/TS) standardized workflows exist, their implementation in clinical practice is underdeveloped. We aimed to assess the applicability of ISO and CEN/TS standards in a real-world clinical setting, with a particular focus on evaluating the impact of preanalytical parameters and hemolysis on liquid biopsy analysis.
METHODS
We evaluated 659 peripheral blood samples from advanced prostate cancer patients against ISO and CEN/TS standards and documented all essential criteria, including tube draw order, filling level, temperature, and time tracking from blood draw to storage. We assessed hemolysis and its effect on circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) analysis.
RESULTS
Our results demonstrated a high compliance rate, with 96.2% (634/659) of samples meeting essential ISO and CEN/TS criteria. We did not observe a significant impact on ctDNA or CTC detection rates between hemolytic and nonhemolytic samples. Hemolysis was identified in 12.9% (40/311) of plasma samples from our advanced prostate cancer cohort, and within the draw order of 5 blood collection tubes, hemolysis did not significantly increase from tube 1 to 5. In total, 83.8% (552/659) of blood collection tubes had high fill levels above 80% of nominal filling level.
CONCLUSIONS
Our study demonstrates the feasibility and benefits of adhering to ISO and CEN/TS standards in a clinical liquid biopsy study. The standards revealed that hemolysis occurred frequently but did not impair downstream ctDNA and CTC analysis in our cohort of advanced prostate cancer patients.
PubMed: 38958115
DOI: 10.1093/clinchem/hvae079 -
Advanced Materials (Deerfield Beach,... Jun 2024Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and the third leading cause for cancer-related death worldwide. The tumor is...
Multicompartment Polyion Complex Micelles Based on Triblock Polypept(o)ides Mediate Efficient siRNA Delivery to Cancer-Associated Fibroblasts for Antistromal Therapy of Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and the third leading cause for cancer-related death worldwide. The tumor is difficult-to-treat due to its inherent resistance to chemotherapy. Antistromal therapy is a novel therapeutic approach, targeting cancer-associated fibroblasts (CAF) in the tumor microenvironment. CAF-derived microfibrillar-associated protein 5 (MFAP-5) is identified as a novel target for antistromal therapy of HCC with high translational relevance. Biocompatible polypept(o)ide-based polyion complex micelles (PICMs) constructed with a triblock copolymer composed of a cationic poly(l-lysine) complexing anti-MFAP-5 siRNA (siMFAP-5) via electrostatic interaction, a poly(γ-benzyl-l-glutamate) block loading cationic amphiphilic drug desloratatine (DES) via π-π interaction as endosomal escape enhancer and polysarcosine poly(N-methylglycine) for introducing stealth properties, are generated for siRNA delivery. Intravenous injection of siMFAP-5/DES PICMs significantly reduces the hepatic tumor burden in a syngeneic implantation model of HCC, with a superior MFAP-5 knockdown effect over siMFAP-5 PICMs or lipid nanoparticles. Transcriptome and histological analysis reveal that MFAP-5 knockdown inhibited CAF-related tumor vascularization, suggesting the anti-angiogenic effect of RNA interference therapy. In conclusion, multicompartment PICMs combining siMFAP-5 and DES in a single polypept(o)ide micelle induce a specific knockdown of MFAP-5 and demonstrate a potent antitumor efficacy (80% reduced tumor burden vs untreated control) in a clinically relevant HCC model.
PubMed: 38958110
DOI: 10.1002/adma.202404784 -
Small Methods Jul 2024Gliomas, the predominant form of brain cancer, comprise diverse malignant subtypes with limited curative therapies available. The insufficient understanding of their...
Gliomas, the predominant form of brain cancer, comprise diverse malignant subtypes with limited curative therapies available. The insufficient understanding of their molecular diversity and evolutionary processes hinders the advancement of new treatments. Technical complexities associated with formalin-fixed paraffin-embedded (FFPE) clinical samples hinder molecular-level analyses of gliomas. Current single-cell RNA sequencing (scRNA-seq) platforms are inadequate for large-scale clinical applications. In this study, automated snRandom-seq is developed, a high-throughput single-nucleus total RNA sequencing platform optimized for archival FFPE samples. This platform integrates automated single-nucleus isolation and droplet barcoding systems with the random primer-based scRNA-seq chemistry, accommodating a broad spectrum of sample types. The automated snRandom-seq is applied to analyze 116 492 single nuclei from 17 FFPE samples of various glioma subtypes, including rare clinical samples and matched primary-recurrent glioblastomas (GBMs). The study provides comprehensive insights into the molecular characteristics of gliomas at the single-cell level. Abundant non-coding RNAs (ncRNAs) with distinct expression profiles across different glioma clusters and uncovered promising recurrence-related targets and pathways in primary-recurrent GBMs are identified. These findings establish automated snRandom-seq as a robust tool for scRNA-seq of FFPE samples, enabling exploration of molecular diversities and tumor evolution. This platform holds significant implications for large-scale integrative and retrospective clinical research.
PubMed: 38958078
DOI: 10.1002/smtd.202301801 -
The Journal of Small Animal Practice Jul 2024The aim was to assess the technical success of percutaneous ultrasound-guided fine needle aspirates of gastrointestinal wall lesions and evaluate predictors of success....
OBJECTIVES
The aim was to assess the technical success of percutaneous ultrasound-guided fine needle aspirates of gastrointestinal wall lesions and evaluate predictors of success. Secondary aims included comparing the cytological diagnosis with histopathology, evaluating the utility of concurrent locoregional lymph node cytology and assessing the procedure's complication rate.
MATERIAL AND METHODS
Gastrointestinal wall cytology from 75 dogs and 70 cats obtained between 2018 and 2023 were reviewed and categorised as successful (resulting in a diagnostic cytology report) and accurate (resulting in the correct diagnosis when compared to histopathology). Unsuccessful fine needle aspirates, not submitted for cytology, were not recorded. Variables recorded included animal signalment, lesion and lymph node's appearance on ultrasound, size, location, number of smears submitted and experience of the ultrasonographer.
RESULTS
One hundred and fifty-two reports were analysed. Eighty-eight (58%) were successful: three normal epithelium, 21 inflammatory processes and 64 neoplasms. Variables associated with increased technical success included description of a mass, higher number of slides submitted and thickness of gastrointestinal lesion on ultrasound. Comparison with histopathology, performed for 17 lesions, showed discrepancies in eight, complete agreement in seven and partial in two. Eighty-four loco-regional lymph nodes were sampled, of which, 67 were successful (80%) and 52 brought additional clinical information (supporting GI wall cytology or diagnosing neoplasia not identified on GI wall cytology). No complication strictly attributable to gastrointestinal wall sampling was reported but when possibly related, death of the patient occurred in 2.5% of cases.
CLINICAL SIGNIFICANCE
Ultrasound-guided fine needle aspirate of gastrointestinal wall had moderate accuracy and was unsuccessful in 42% of cases, but technical success increased when sampling mass lesions, thicker intestinal layers and submitting more slides.
PubMed: 38958024
DOI: 10.1111/jsap.13759 -
Nucleic Acid Therapeutics Jul 2024Although has been considered an undruggable target, alterations confer poor prognosis in many pediatric and adult cancers. The novel -specific inhibitor BGA002 is an...
Although has been considered an undruggable target, alterations confer poor prognosis in many pediatric and adult cancers. The novel -specific inhibitor BGA002 is an antigene peptide nucleic acid oligonucleotide covalently bound to a nuclear localization signal peptide. In the present study, we characterized the pharmacokinetics (PK) of BGA002 after single and repeated administration to mice using a novel specific enzyme-linked immunosorbent assay. BGA002 concentrations in plasma showed linear PK, with dose proportional increase across the tested dose levels and similar exposure between male and female and between intravenous and subcutaneous route of administration. Repeated dosing resulted in no accumulation in plasma. Biodistribution up to 7 days after single subcutaneous administration of [C]-radiolabeled BGA002 showed broad tissues and organ distribution (suggesting a potential capability to reach primary tumor and metastasis in several body sites), with high concentrations in kidney, liver, spleen, lymph nodes, adrenals, and bone marrow. Remarkably, we demonstrated that BGA002 concentrates in tumors after repeated systemic administrations in three mouse models with amplification (neuroblastoma, rhabdomyosarcoma, and small-cell lung cancer), leading to a significant reduction in tumor weight. Taking into account the available safety profile of BGA002, these data support further evaluation of BGA002 in patients with -positive tumors.
PubMed: 38957973
DOI: 10.1089/nat.2024.0005 -
Surgical Infections Jul 2024Surgical site infections (SSIs) are a substantial healthcare burden in low- and middle- income countries. "Clean Cut" is a checklist-based infection prevention and...
Surgical site infections (SSIs) are a substantial healthcare burden in low- and middle- income countries. "Clean Cut" is a checklist-based infection prevention and control (IPC) program intended to improve compliance to peri-operative IPC standards. We aim to study the short-term and long-term impact of its implementation in a tertiary care cancer referral center. This was a single institute, prospective interventional study. Patients undergoing elective head-neck surgical procedures were included. The "Clean Cut" program consisting of surveillance, audits, and IPC training was implemented for 6 months, after which there was no active oversight. Post-intervention (T2) and 1-year follow-up (T3) data regarding compliance to core IPC practices and SSI rates were compared with baseline (T1). One hundred eighty six patients were included with 50 (26.9%), 86 (46.2%), and 50 (26.9%) patients at T1, T2, and T3, respectively. At baseline, teams complied with a mean of 3.56 of the six critical components of infection control processes which rose to 4.66 (p < 0.001) at T2, but decreased to 4.02 at T3 (p = 0.053). The SSI rate at baseline decreased significantly after Clean Cut implementation [16 (32%) vs. 12 (13.95%), p = 0.012], but returned to baseline levels after 1 year [17 (34%), p = 0.006]. Implementation of the "Clean Cut" program increases compliance to infection control processes and reduces SSI rates in the short term. Without continuing oversight, these rates return to baseline values after 1 year.
PubMed: 38957964
DOI: 10.1089/sur.2023.334 -
American Journal of Hematology Jul 2024Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an aggressive B-cell lymphoma associated with EBV infection... (Review)
Review
DISEASE OVERVIEW
Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an aggressive B-cell lymphoma associated with EBV infection included in the WHO classification of lymphoid neoplasms since 2016. Although historically associated to poor prognosis, outcomes seem to have improved in the era of chemoimmunotherapy.
DIAGNOSIS
The diagnosis is established through meticulous pathological evaluation. Detection of EBV-encoded RNA (EBER) is the standard diagnostic method. The ICC 2022 specifies EBV+ DLBCL, NOS as occurring when >80% of malignant cells express EBER, whereas the WHO-HAEM5 emphasizes that the majority of tumor cells should be EBER positive without setting a defined threshold. The differential diagnosis includes plasmablastic lymphoma, DLBCL associated with chronic inflammation, primary effusion lymphoma, among others.
RISK-STRATIFICATION
The International Prognostic Index (IPI) and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers.
MANAGEMENT
Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. Therefore, inclusion of patients in clinical trials when available is recommended. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.
PubMed: 38957951
DOI: 10.1002/ajh.27430 -
JAAD International Sep 2024National cancer reporting-based registry data, although robust, lacks granularity for incidence trends. Expert opinion remains conflicted regarding the possibility of...
BACKGROUND
National cancer reporting-based registry data, although robust, lacks granularity for incidence trends. Expert opinion remains conflicted regarding the possibility of melanoma overdiagnosis in the context of rising incidence without a corresponding rise in mortality.
OBJECTIVE
To characterize 10- and 50-year trends in melanoma incidence and mortality.
METHODS
Multicenter, population-based epidemiologic study utilizing the Rochester Epidemiology Project for Olmsted County, Minnesota residents diagnosed with melanoma from 01/01/1970 to 12/21/2020. Age- and sex-adjusted incidence and disease-specific mortality are calculated.
RESULTS
Two thousand three hundred ten primary cutaneous melanomas were identified. Current age- and sex-adjusted incidence rates increased 11.1-fold since 1970s ( < .001). Over the last decade, there is an overall 1.21-fold ( < .002) increase, with a 1.36-fold increase ( < .002) among females and no significant increase among males (1.09-fold increase, < .329). Melanoma-specific mortality decreased from 26.7% in 1970s to 1.5% in 2010s, with a hazard ratio (HR) reduction of 0.73 ( < .001) per 5-year period. Increased mortality was associated with Breslow thickness (HR 1.35, < .001), age at diagnosis (HR 1.13, = .001) left anatomic site (HR 1.98, = .016), and nodular histogenic subtype (HR 3.08, < .001).
LIMITATIONS
Retrospective nature and focused geographic investigation.
CONCLUSION
Melanoma incidence has continued to increase over the past decade, most significantly in females aged 40+. Trend variations among age and sex cohorts suggests external factors beyond overdiagnosis may be responsible. Disease-specific mortality of melanoma continues to decrease over the last 50 years.
PubMed: 38957842
DOI: 10.1016/j.jdin.2024.04.010