The effect of 1.5 T cardiac magnetic resonance on human circulating leucocytes.

Aims: Investigators have proposed that cardiovascular magnetic resonance (CMR) should have restrictions similar to those of ionizing imaging techniques. We aimed to investigate the acute effect of 1.5 T CMR on leucocyte DNA integrity, cell counts, and function in vitro, and in a large cohort of patients in vivo. Methods and results: In vitro study: peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers, and histone H2AX phosphorylation (γ-H2AX) expression, leucocyte counts, and functional parameters were quantified using flow cytometry under the following conditions: (i) immediately following PBMC isolation, (ii) after standing on the benchside as a temperature and time control, (iii) after a standard CMR scan. In vivo study: blood samples were taken from 64 consecutive consenting patients immediately before and after a standard clinical scan. Samples were analysed for γ-H2AX expression and leucocyte counts. CMR was not associated with a significant change in γ-H2AX expression in vitro or in vivo, although there were significant inter-patient variations. In vitro cell integrity and function did not change with CMR. There was a significant reduction in circulating T cells in vivo following CMR. Conclusion: 1.5 T CMR was not associated with DNA damage in vitro or in vivo. Histone H2AX phosphorylation expression varied markedly between individuals; therefore, small studies using γ-H2AX as a marker of DNA damage should be interpreted with caution. Cardiovascular magnetic resonance was not associated with loss of leucocyte viability or function in vitro. Cardiovascular magnetic resonance was associated with a statistically significant reduction in viable leucocytes in vivo.

The Value of Cardiovascular Magnetic Resonance in Heart Transplant Patients.

Heart transplant patients present a unique set of anatomical and pathophysiological considerations. Patients often present non-specifically, requiring a low index for further investigation. Accurate assessment with standard imaging modalities can be difficult, and cardiovascular magnetic resonance (CMR) is becoming an increasingly useful modality in the assessment of heart transplant patients. This review describes the anatomy of the transplanted heart and typical CMR appearances and discusses the role of CMR in heart transplant disease.

Real-world outcomes of cisplatin, capecitabine, and gemcitabine with either epirubicin (PEXG) or docetaxel (PDXG) as first-line palliative treatment in metastatic or unresectable locally advanced pancreatic adenocarcinoma.

BACKGROUND: First-line palliative chemotherapy regimens in advanced pancreatic adenocarcinoma include triplet chemotherapy with 5-fluorouracil, oxaliplatin, and irinotecan, and the doublet of nab-paclitaxel plus gemcitabine. Use of triplet chemotherapy in real-world populations is limited by tolerability and nab-paclitaxel is not universally available. Regimens using the combination of cisplatin, capecitabine, gemcitabine, and either epirubicin or docetaxel may be better tolerated, more widely available, and similarly effective, but no published real-world data exist. METHODS: A retrospective cohort review of patients with metastatic or unresectable locally advanced pancreatic adenocarcinoma treated with first-line palliative cisplatin, capecitabine, gemcitabine, and either epirubicin or docetaxel chemotherapy at Auckland City Hospital between July 1, 2013 and July 30, 2020. The primary outcome was overall survival (OS). Secondary outcomes were rates of grade 3 or 4 hematological toxicity, rate of febrile neutropenia, number of cycles received, and reasons for discontinuation. RESULTS: Eighty-eight patients were included. Median age was 66 years (range 39-79), 28.4% had unresectable, locally advanced disease and 71.6% metastatic disease. Median OS was 8.5 months. Patients stopped treatment due to disease progression (53.4%), completing 12 cycles (19.3%), or toxicity (10.2%). Grade 4 neutropenia was experienced by 21.6%; 10.2% had febrile neutropenia. There were four treatment-related deaths. CONCLUSION: This retrospective study in a real-world population demonstrates that chemotherapy with cisplatin, capecitabine, and gemcitabine with epirubicin (PEXG) or docetaxel (PDXG) had similar effectiveness to more commonly used combination regimens. PDXG/PEXG are viable alternatives to nab-paclitaxel plus gemcitabine in countries that have restricted drug funding.

Genomic Testing in Patients with Metastatic Castration-resistant Prostate Cancer: A Pragmatic Guide for Clinicians.

CONTEXT: Genomic testing is becoming increasingly important in patients with advanced prostate cancer (PC) and is being incorporated in clinical practice to guide treatment. OBJECTIVE: To review the current understanding of genomic alterations and the status of genomic testing in patients with metastatic castration-resistant PC (mCRPC), and the potential use of genomic tests in clinical practice. EVIDENCE ACQUISITION: We reviewed recent publications (past 15 yr) from PubMed, proceedings of scientific conferences, and published guidelines. Reports on mCRPC in the following areas were selected: development, testing, and validation of techniques for identifying genomic alterations; molecular characterization; and trials of genetically targeted therapies. EVIDENCE SYNTHESIS: mCRPC tumors harbor molecular alterations that are possible targets for treatment, and a number of therapies are in development to exploit these alterations (eg, PD-1 inhibitors, PARP inhibitors, tyrosine kinase inhibitors). Next-generation sequencing of DNA from tumor tissue can identify somatic alterations that would not be identified by germline testing. Work is ongoing to evaluate the use of less invasive somatic testing methods (eg, sequencing of cell-free circulating tumor DNA). Current international guidelines recommend germline and/or somatic testing for men with advanced and/or high-risk PC regardless of family history to identify those with homologous recombination repair gene mutations or mismatch repair defects/microsatellite instability who may be eligible for treatment with a PARP inhibitor or pembrolizumab, respectively. CONCLUSIONS: Genomic testing for mCRPC may provide information on prognostic, predictive, and resistance biomarkers. Although the incorporation of testing into clinical practice remains challenging, routine genomic testing of men with advanced PC is recommended to guide management and treatment decisions. PATIENT SUMMARY: Similar to many cancers, prostate cancer is caused by defects in the cancer's DNA, which are called genetic or genomic defects. New treatments targeting these defects are approved for metastatic castration-resistant prostate cancer. Specific new tests are under development to detect these potentially treatable genetic defects.

Acid violence in Cambodia: the human, medical and surgical implications.

INTRODUCTION: Acid violence is the deliberate use of acid to attack another human being. Such attacks leave a terrible human, medical and surgical legacy. This study, from one of the largest cohorts of acid attack victims to date, provides insights into Cambodia's unique demographics of such attacks, as well as the human cost and necessary surgical interventions. METHODS: A retrospective cohort consisting of all patients presenting to the Children's Surgical Centre, Phnom Penh with acid burns from 1 January 2000 to 1 January 2013 was identified and information retrieved from their hospital records. RESULTS: 254 patients were identified. Males and females were almost equally likely to be victims of an acid attack (48.4% and 51.6% respectively). There was no significant association between victim and assailant gender (p=0.475). The face (78.0%), neck (51.5%) and chest (49.0%) were the most frequently affected body areas. The median total surface body area affected by acid burns was 7.0%. The mortality rate from acid assault was 2.0%. Patients required an average of 2.0 operations, ranging from 0 to 18. CONCLUSIONS: Acid violence in Cambodia has a complex demographic which is different to many other developing countries and requires more investigation. Tougher legislation is required to reduce the incidence of these horrific crimes.