PET Molecular Imaging in Breast Cancer: Current Applications and Future Perspectives.

Positron emission tomography (PET) plays a crucial role in breast cancer management. This review addresses the role of PET imaging in breast cancer care. We focus primarily on the utility of 18F-fluorodeoxyglucose (FDG) PET in staging, recurrence detection, and treatment response evaluation. Furthermore, we delve into the growing interest in precision therapy and the development of novel radiopharmaceuticals targeting tumor biology. This includes discussing the potential of PET/MRI and artificial intelligence in breast cancer imaging, offering insights into improved diagnostic accuracy and personalized treatment approaches.

Morally injurious events and posttraumatic embitterment disorder in U.K. health and social care professionals during COVID-19: A longitudinal web survey.

OBJECTIVE: To longitudinally estimate the prevalence and predictors of potentially morally injurious events (PMIEs) and posttraumatic embitterment disorder (PTED) and in U.K. health and social care workers (HSCWs) during the COVID-19 pandemic. Additionally, to investigate the mechanism by which PMIEs increase embitterment by lowering personal belief in procedural justice, that is, the belief that they experience fair processes. METHOD: An online longitudinal survey was hosted on Qualtrics between September-October 2020 and September-November 2021. Using Prolific, 400 HSCWs aged 18 or above and working in the United Kingdom during the pandemic were recruited. PMIEs were assessed using the Moral Injury Events Scale, and PTED was assessed using the PTED self-rating scale. Potential predictors were measured using surveys of exposure to occupational stressors, optimism, pessimism, self-esteem, resilient coping style, consideration of future consequences, and personal just world beliefs. RESULTS: Seventy-one percent of participants experienced at least one COVID-related PMIE and 20% displayed clinically relevant signs of PTED at Time 2 in 2021. Exposure to occupational stressors increased the risk of experiencing PMIEs and PTED, whereas personal belief in a procedurally just world protected against transgressions by others and betrayal PMIEs. Self-esteem was protective, and a resilient coping style was a risk for experiencing betrayal. PMIEs increased embitterment by lowering personal belief in procedural justice over a 12-month period. CONCLUSIONS: PMIEs and PTED are being experienced by U.K. HSCWs in 2020 and 2021, particularly in those exposed to work-related stressors. Exposure to PMIEs increases the risk of embitterment by lowering belief in procedural justice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Time on our side: An exploratory investigation of the relationship between psychiatric disorder and time attitudes.

Time attitudes indicate how individuals feel about the past, present, and future. A growing body of research has demonstrated that scores on the Adolescent and Adult Time Inventory-Time Attitudes Scale relate meaningfully to a variety of measures of well-being and psychiatric symptomatology. To date, no study has examined how (if at all) Time Attitudes scores relate to psychiatric disorder. The present study used an existing clinical cohort (N = 68) and assessed the associations among time attitudes, lifetime disorder, and a retrospective measure of childhood trauma. Preliminary analyses revealed that mean scores of the six time attitudes in the present study did not differ substantially from scores reported in a recent meta-analysis. Correlations between time attitude scores and retrospective trauma scores were particularly large for past negative and past positive. Individuals with no past or current disorder reported substantially higher positive attitudes and substantially lower negative attitudes than those without a disorder across all three time periods with interpretable effect sizes. Finally, past negative time attitudes scores were significantly associated with lifetime mood or anxiety disorder, prior to adjustment for scores on self-reported childhood trauma. These results suggest that time attitudes could be a variable of consequence beyond feelings of general well-being and beyond psychiatric symptoms. More studies with larger sample sizes are required in order to examine the relationship between time attitudes and psychiatric disorder.

Comparative subchronic toxicity of copper and a tertiary copper mixture to early life stage rainbow trout (Oncorhynchus mykiss): impacts on growth, development, and histopathology.

This research aimed to characterize and compare the subchronic impacts of Cu to a Cu, Cd, and Zn mixture in early life stages of rainbow trout (Oncorhynchus mykiss) by examining uptake, survival, growth, development, and histopathology parameters. To accomplish this, rainbow trout were exposed for 31 days from eyed embryos to the swim-up fry life stage to waterborne Cu (31, 47, 70, and 104 µg/L) individually or as mixture containing Cd (4.1, 6.2, 9.3, and 14 µg/L) and Zn (385, 578, 867, and 1300 µg/L). Exposures elicited pronounced effects on survival when Cu was administered as a mixture (LC25 = 32.9 µg/L Cu) versus individually (LC25 = 46.3 µg/L Cu). Mixtures of Cu, Cd, and Zn also elicited more pronounced sublethal toxicity relative to equivalent Cu treatments with respect to reduced yolk sac resorption and increased incidence and/or severity of gill, liver, and kidney lesions. Our findings of reduced body weight (EC10, Cu = 55.0 µg/L Cu; EC10, Cu+Cd+Zn = 58.9 µg/L Cu), yolk sac resorption (LOECCu = 70 µg/L Cu; LOECCu+Cd+Zn = 70 µg/L Cu), coelomic fat (LOECCu = 47 µg/L Cu; LOECCu+Cd+Zn = 70 µg/L Cu), and increased hepatocellular cytoplasmic vacuolation (LOECCu = 70 µg/L Cu; LOECCu+Cd+Zn = 47 µg/L Cu) collectively indicate a complicated metabolic interference by metals in exposed fish. These lethal and sublethal effects observed in the laboratory could translate to reduced survival and fitness of wild salmonid populations inhabiting waterbodies receiving wastewater or runoff containing multiple metals at elevated concentrations.

Narrative review-diagnosing and managing malignant epidural spinal cord compression: an evidence-based approach.

Background and Objective: Malignant spinal cord compression (MSCC) is a medical emergency. Clinical deterioration can occur quickly and irreversibly. MSCC is caused predominantly by metastatic cancer spread to the epidural space by epithelial or haematological malignancies. The primary diagnostic test is full-spine magnetic resonance imaging (MRI) since it has excellent soft tissue spatial resolution, and MSCC is multi-level in around one-third of cases. The modalities of therapy for MSCC are steroids, radiotherapy, and surgery. Radiotherapy is a mainstay of treatment since indications for surgery are limited. Recently randomised clinical trials exploring long course vs. short course radiotherapy have been undertaken as well as novel incorporation of stereotactic ablative radiotherapy (SABR). This review summarises these recent trials and identifies and discusses published data for novel treatment paradigms of MSCC. Methods: Multiple medical databases were searched through January 7th, 2023 and identified relevant studies that examined the use of radiotherapy with or without surgery in the management of MSCC. Key Content and Findings: In addition to a detailed overview of the pathophysiology and diagnosis of cord compression, we also examine all recent phase III clinical trials to date on the use of conventional radiotherapy in managing MSCC. Our review also provides a comprehensive summary and discussion of the novel approaches to the management of cord compression, including the role of SABR and a non-traditional surgical approach as well. Conclusions: Shorter courses of radiotherapy can be considered for poor prognosis patients. For favourable prognosis patients, longer courses of treatment provide more durable local control. An emerging treatment paradigm is a hybrid approach of surgery and SABR, however this has not been studied prospectively.

Indoor air quality in remote first nations communities in Ontario, Canada.

A recent study of the health of Indigenous children in four First Nations Communities in remote northwestern Ontario found that 21% of children had been admitted to hospital for respiratory infections before age 2 years. Here we report a detailed analysis of the housing conditions in these communities. We employed a variety of statistical methods, including linear regression, mixed models, and logistic regression, to assess the correlations between housing conditions and loadings of biocontaminants (dust mite allergens, fungal glucan, and endotoxin) and indoor concentrations of PM2.5, CO2, benzene, and formaldehyde. The houses (n = 101) were crowded with an average of approximately 7 people. Approximately 27% of the homes had sustained CO2 concentrations above 1500 ppm. Most homes had more than one smoker. Commercial tobacco smoking and the use of non-electric heating (e.g., wood, oil) were associated with increased fine particle concentrations. Over 90% of the homes lacked working Heat Recovery Ventilators (HRVs), which was associated with increased fine particle concentrations and higher CO2. Of the 101 homes, 12 had mold damage sufficient to increase the relative risk of respiratory disease. This resulted from roof leaks, through walls or around the windows due to construction defects or lack of maintenance. A similar percentage had mold resulting from condensation on windows. Endotoxin loadings were much higher than any previous study in Canada. This work provides evidence for the need for more effort to repair existing houses and to ensure the HRVs are properly installed and maintained.

Skin morbidity in Indigenous children in relation to housing conditions in remote communities in Northwestern Ontario, Canada.

BACKGROUND: Elevated rates of eczema and skin infections in Canadian First Nation (FN) communities are of concern to families, community leaders and healthcare professionals. AIM: To determine whether skin morbidity was associated with indoor environmental quality factors in Canadian FN children living in remote communities. METHODS: We quantified indoor environmental quality (IEQ) in the homes of FN children aged < 4 years of age living in four remote communities in the Sioux Lookout region of Northwestern Ontario, Canada. We conducted a quantitative housing inspection, including measuring surface area of mould (SAM), and monitored air quality for 5 days in each home, including carbon dioxide and relative humidity and quantified endotoxin in settled floor dust. We reviewed the medical charts of participating children for skin conditions and administered a health questionnaire. Relationships between IEQ and skin infections or eczema were evaluated using multivariable regression. RESULTS: In total, 98 children were included in the descriptive analyses, of whom 86 had complete data and were evaluated in multivariate analyses for dermatological outcomes (mean age 1.6 years). Of these 86 children, 55% had made ≥ 1 visits to the local health centre (HC) for skin and soft tissue infections and 25.5% for eczema. Unexpectedly, annualized eczema visits were inversely associated with SAM (RR = 0.14; 95% CI 0.01-0.93). There was a trend suggesting an inverse relationship between endotoxin and HC encounters for eczema and skin and soft tissue infections. CONCLUSION: Skin infections were common in this population of FN children. IEQ did not appear to be associated with skin infections or eczema. Mould exposure appeared to be inversely associated with HC encounters for eczema, possibly related to complex microorganism-host interactions occurring early in life.

The inter-relatedness and demographic predictors of physical activity, self-rated health, and mental well-being: A three-wave study in secondary school children.

INTRODUCTION: The World Health Organisation recommends that children and adolescents engage in at least 60 min of moderate-to-vigorous physical activity per day. Previous research has shown that physical activity is related to other constructs such as mental well-being and self-rated health. This study examined the inter-relatedness of these constructs in Northern Irish school children. METHODS: This study was a secondary analysis of data gathered as part of a longitudinal study. Participants were n = 1791 adolescents in their final years of secondary (high) school (age range 15-18; female = 64.6%). Data were gathered on three occasions over a 2-year period on self-rated health, physical activity, mental well-being, heavy episodic drinking, lifetime smoking, psychological and somatic symptoms, as well as a range of socio-demographic measures. RESULTS: Descriptive results showed extremely low levels of self-reported physical activity within the past week, with <6% of the sample attaining the WHO guidelines at each wave of data collection. There were significant gender differences on all variables assessed. Results further showed a small-sized relationship (statistically significant for girls only) between physical activity and mental well-being. There was also a small-sized relationship between physical activity and self-rated health. Notably, effect sizes for the relationship between self-rated health and both physical activity and mental well-being were higher. In terms of socio-demographic predictors of lower physical activity, being female, lifetime cigarette smoking, and higher somatic and psychological symptoms were all statistically significant factors. CONCLUSION: Self-rated health emerged as the most important predictor of physical activity among adolescents.

The Subjective Impact and Timing of Adversity Scale: A Feasibility Study Using Cross-Sectional and Longitudinal Data.

This study assessed the feasibility of a multi-domain measure of the occurrence, impact, and timing of childhood/adolescent psychological adversity exposure, the Subjective Impact and Timing of Adversity Scale (SITA). Participants were from among those who had previously participated in two waves of data collection when aged approximately 14 and 21 years. Internal consistency estimates at both online and interview stages were acceptable for all SITA domains (with the exception of parental loss). SITA domain scores correlated meaningfully with scores on other scales and psychological measures, supporting convergent validity. Those with lifetime psychiatric diagnoses scored significantly higher on SITA domains than those not meeting diagnostic threshold. There was evidence of the importance of both the subjective impact and timing of adversity with regard to psychiatric diagnoses. The study demonstrates the viability of the SITA; however, further studies are required to substantiate these findings in larger samples.

Oncogenic alterations reveal key strategies for precision oncology in melanoma treatment.

Background: Molecular profiling with next-generation sequencing (NGS) has been applied in multiple solid tumors, including melanomas, to identify potential drug targets. However, the association between clinical outcomes and the molecular alterations has not yet been fully clarified. Methods: A total of 108 patients with melanoma were included in this study, 95 of whom had both sequencing data and clinical outcomes were collected. We analyzed the genetic alterations of 108 malignant melanoma patients using the OncoCare panel, which covers 559 genes. Results: A model was also established to predict side effects through a combination analysis of clinical data and somatic variants, yielding an area under the receiver operating characteristic curve (AUROC) score of 0.8. We also identified epidermal growth factor receptor (EGFR) mutation was excellent predictor for progression-free survival (PFS) for patient who received immunotherapy (log-rank P=0.01), while tumor mutation burden (TMB) was found to not be significantly associated with PFS (log-rank P=0.87). Combining clinical features with genetic analysis, we found that patients carrying both DNA POLD1/ALOX12B or POLD1/PTPRT mutations had a significantly lower survival rate. Conclusions: Overall, these results demonstrate the benefits of applying NGS clinical panels and shed light on future directions of personalized therapeutics for the treatment of melanoma.

Role of ROR2 in promoting gastric cancer metastasis by enhancing c-JUN-mediated MMP3 transcription.

Background: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a transmembrane receptor that has a complex role in cancer, acting either to promote or inhibit tumor progression in different tumor types. The effect of ROR2 on gastric cancer is unclear. Methods: Immunohistochemistry was used to investigate the role of ROR2 in the prognosis of gastric cancer. Transwell assay and a BALB/c nude mice pulmonary metastasis model were used to ascertain the role of ROR2 in promoting metastasis in vitro and in vivo. A protein expression array, chromatin immunoprecipitation (ChIP) assay, and luciferase reporter assay were employed to search for the target genes of ROR2. Results: ROR2 was found to be upregulated in gastric cancer tissues, which was correlated with poor disease-free survival (DFS) and overall survival (OS) in gastric cancer patients. Moreover, ROR2 promoted gastric cancer cell migratory and invasive behaviors in vitro and metastasis in vivo. Further research showed that ROR2 promoted gastric cancer metastasis via upregulation of matrix metalloproteinase 3 (MMP3). Analyses of clinical data indicated that high expression of ROR2 was correlated with a high expression of MMP3. Further study showed that ROR2 activated c-JUN by translocating phosphorylated JNK1/2 into the nucleus, and c-JUN interacted directly with the MMP3 promoter, leading to enhanced MMP3 transcription. Conclusions: We report for the first time that ROR2 is upregulated in gastric cancer, promotes metastasis, and is associated with poor prognosis in gastric cancer. The findings suggest that ROR2 may be a promising prognostic predictor for gastric cancer. Silencing the JNK1/2-c-JUN pathway, thereby inhibiting MMP3 expression, may serve as a promising strategy to inhibit gastric cancer progression.

The McLean Screening Instrument for Borderline Personality Disorder: What, and why in a clinical cohort?

Borderline Personality Disorder is a severe psychiatric disorder with debilitating consequences. Screening for the disorder is problematic as symptoms overlap with other psychiatric disorders. The McLean Screening Instrument (MSI) assesses endorsement (yes/no) of 10 symptoms, with a cut-off of seven indicating potential caseness. Participants were (N = 68) from an established clinical cohort who completed a structured clinical interview, the MSI, the Childhood Trauma Questionnaire, and the Adolescent and Adult Time Attitudes Scale. A proportion (N = 20) also completed a follow-up interview examining their rationale for endorsing MSI items. Total number of MSI items endorsed was meaningfully related to scores on emotional neglect and negative time attitudes. There was substantive overlap between MSI threshold (≥7 items) and lifetime diagnosis of a mental disorder. The stated rationale for endorsing MSI items, was less indicative of personality trait, and was related more to particular developmental periods, one-off episodes, and life-contexts. Additionally, participants conflated constructs such as emptiness with loneliness, and moodiness with general emotionality. Those meeting MSI threshold recalled more childhood emotional neglect, and were more negative about all time periods. It is apparent that scoring of the MSI is driven by prevailing life circumstances as much as enduring personality traits.

A revised and extended systematic review and meta-analysis of the relationship between childhood adversity and adult psychiatric disorder.

This study aimed to systematically review the evidence for an association between adversity experienced in childhood (≤ 17 years old), and the diagnosis of psychiatric disorder in adulthood. Electronic databases (Scopus, Medline (for Ovid), EMBASE, and PsychINFO) were searched for peer-reviewed, longitudinal cohort studies examining child or adolescent exposure to adversity, and adult-diagnosed depression, anxiety, psychotic disorder, eating disorders, substance abuse disorder, illness anxiety disorder, somatoform disorder, or personality disorder. A total of 39 manuscripts were retained. Results revealed a significant association between the following childhood exposures and adult mental disorder (1.24 ≤ Odds ratios ≤ 2.09): bullying (victimhood, and frequency); emotional abuse; neglect; physical abuse; parental loss; and general maltreatment (unspecified and/or multiple adversity exposure). There were opposing results for being a victim and perpetrator of bullying, and the result for sexual abuse was not statistically significant. There was some evidence of a dose-response relationship with those exposed to multiple forms of maltreatment having more two and a half times odds of developing a mental disorder (Odds ratio = 2.59). The result for sexual abuse is likely an artefact of the prospective assessment of this adversity. In summary, there was strong evidence of an association between childhood adversity and later mental illness, and this supports previously reported meta-analyses. The evidence suggests that childhood and adolescence is an important time for risk for later mental illness, and an important period in which to focus intervention strategies for those known to have been exposed to adversity, particularly multiple adversities.

Bioinformatic analysis of cancer-associated fibroblast related gene signature as a predictive model in clinical outcomes and immune characteristics of gastric cancer.

Background: Gastric cancer (GC) has a high incidence and high mortality rate among Asian countries, and distinguishing predictive prognosis biomarkers for GC are essential. Cancer-associated fibroblasts (CAFs) play a significant role in the progression, immune evasion, and therapeutic resistance of GC. Therefore, CAF-associated genes might have huge potential as prognostic biomarkers for predicting tumor progression and survival rate in GC pateints. Methods: A sum of 1,134 GC patients from the The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD), GSE62254, and GSE84437 datasets as well as GC cohorts from Xijing hospital were included. Firstly, we performed univariate Cox regression analysis to identify CAF-associated prognostic genes. Subsequently, the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to develop a CAF gene signature (CAFGS) in the TCGA-STAD training cohort. CAFGS's predictive performance was examined in both the training and validation cohorts, and the relationship between CAFGS and the tumor microenvironment (TME) was investigated by ssGSEA, CIBERSORT, TIMER, and ESTIMATE. Finally, a nomogram of CAFGS was established. Results: Ten CAF-associated genes (ANGPTL4, CPNE8, CST2, HTR1F, IL1RAP, NR1D1, NTAN1, OLFML2B, TMEM259, and VTN) were identified to develop CAFGS. A high CAFGS score represented a worse outcome for GC patients in four cohorts, and a strong correlation was found between CAFGS and the infiltration of immune cells. We showed that CAFs contribute to immune evasion and unfavorable prognoses of GC patients by promoting the formation of an immunosuppressive microenvironment, and a high level of CAF infiltration may attenuate the efficacy of immunotherapy. The nomogram based on CAFGS showed reasonable predictive ability and may deliver great clinical net benefits. Conclusions: We established a CAFGS model with 10 CAF-associated genes that had a great predictive value for GC prognosis and survival rate evaluation. This study could provide a novel insight for investigating the role of CAFs in GC.

Morally injurious events and post-traumatic embitterment disorder in UK health and social care professionals during COVID-19: a cross-sectional web survey.

OBJECTIVE: To estimate the prevalence and predictors of morally injurious events (MIEs) and post-traumatic embitterment disorder (PTED) in UK health and social care professionals during the COVID-19 pandemic. DESIGN: Cross-sectional study. SETTING: September-October 2020 in the UK. Online survey hosted on Qualtrics, and recruited through Prolific. PARTICIPANTS: 400 health and social care workers, aged 18 or above and living and working in the UK during the pandemic. MAIN OUTCOME MEASURES: MIEs were assessed using the Moral Injury Events Scale and PTED was assessed using the PTED self-rating scale. Potential predictors were measured using surveys of exposure to occupational stressors, optimism, self-esteem, resilient coping style, consideration of future consequences and personal belief in a just world. RESULTS: 19% of participants displayed clinical levels of PTED, and 73% experienced at least one COVID-related MIE. Exposure to occupational stressors increased the risk of experiencing PTED and MIEs, whereas personal belief in a procedurally just world, which is the belief that they experienced fair processes, was a protective mechanism. CONCLUSIONS: MIEs and PTED are being experienced by UK health and social care professionals, particularly in those exposed to work-related stressors.

Housing conditions and respiratory morbidity in Indigenous children in remote communities in Northwestern Ontario, Canada.

BACKGROUND: Rates of lower respiratory tract infection (LRTI) among First Nations (FN) children living in Canada are elevated. We aimed to quantify indoor environmental quality (IEQ) in the homes of FN children in isolated communities and evaluate any associations with respiratory morbidity. METHODS: We performed a cross-sectional evaluation of 98 FN children (81 with complete data) aged 3 years or younger, living in 4 FN communities in the Sioux Lookout region of Northern Ontario. We performed medical chart reviews and administered questionnaires. We performed a housing inspection, including quantifying the interior surface area of mould (SAM). We monitored air quality for 5 days in each home and quantified the contaminant loading of settled floor dust, including endotoxin. We analyzed associations between IEQ variables and respiratory conditions using univariable and multivariable analyses. RESULTS: Participants had a mean age of 1.6 years and 21% had been admitted to hospital for respiratory infections before age 2 years. Houses were generally crowded (mean occupancy 6.6 [standard deviation 2.6, range 3-17] people per house). Serious housing concerns were frequent, including a lack of functioning controlled ventilation. The mean SAM in the occupied space was 0.2 m2. In multivariable modelling, there was evidence of an association of LRTI with log endotoxin (p = 0.07) and age (p = 0.02), and for upper respiratory tract infections, with SAM (p = 0.07) and age (p = 0.03). Wheeze with colds was associated with log endotoxin (p = 0.03) and age (p = 0.04). INTERPRETATION: We observed poor housing conditions and an association between endotoxin and wheezing in young FN children living in Northern Ontario.

Radiotherapy planning of lymphomas: role of metabolic imaging with PET/CT.

Accurate target delineation is an absolute requirement for modern radiotherapy planning. Historically, structural imaging modalities have been used for this purpose, but there is a considerable role for functional imaging with PET/CT to contribute in this area. PET/CT's role in radiotherapy planning is well established and its use is indispensable in the clinical management of the lymphomas, particularly Hodgkin Lymphoma. A crucial use of PET/CT is as a baseline scan for delineation of the initial lymphomatous involvement, since this will determine the contouring of the gross-, clinical- and planning-target volumes (GTV, CTV, PTV). This article reviews the principles of contemporary radiotherapy, examines the evidence for the contribution of PET/CT to radiotherapy planning in lymphoma and the practicalities and challenges of applying this powerful technology to this situation.

Searching for Something Positive in Future Negative: The Adolescent and Adult Time Inventory-Time Attitudes Scale.

The Adolescent and Adult Time Inventory-Time Attitudes Scale (AATI-TA) measures emotional engagement with the past, present, and future, and scores have been shown to relate meaningfully to health outcomes. For past, present, and future, five items are used to assess both positive and negative attitudes. Although evidence for the hypothesized six-factor solution has been widely reported, some studies have indicated problems with the Future Negative items. Given that a large and growing literature has emerged on the six-factor AATI-TA, and that AATI-TA scores have shown much better and more consistent fit than other temporal psychology measures, we sought to investigate the future negative factor in detail. Secondary analyses were performed on two datasets. The first was a University convenience sample (N = 410) and the second was an adolescent sample (N = 1,612). Confirmatory factor analyses revealed that the fit for the five Future Negative items was poor. Modification indices suggested that a correlated error term between Items 4 and 10 would result in good fit, and this was indeed the case. Models without Item 4 or Item 10 also yielded acceptable fit. Analyses using all four operationalizations of Future Negative (original scale, without Item 4 or Item 10, or with the correlated error between Items 4 and 10) to predict symptoms of anxiety and depression, and emotional self-efficacy revealed minor differences in the predictive validity coefficients. Potential ways forward, including a correlated error term or the dropping or replacement of Item 10, are discussed.

Brain metastases: increasingly precision medicine-a narrative review.

OBJECTIVE: To broadly review the modern management of brain metastases. BACKGROUND: Brain metastases are the commonest neurological manifestation of cancer and a major cause of morbidity in cancer patients. Brain metastases are increasing in frequency, as a result of longer life expectancy of cancer patients, more sensitive methods for brain metastasis detection and an ageing population. The proportional incidence of brain metastases according to cancer of origin, from greatest to least, is lung cancer, melanoma, renal, breast and colorectal cancers. Patients with lung cancer and melanoma are most likely to have brain metastases at diagnosis. Brain metastases cause a variety of symptoms, depending on their size and location, whether they cause mass effect and oedema, compression of the brain parenchyma, or focal neurological deficits. The major differential diagnoses of brain metastases include primary tumours and vascular/inflammatory lesions. Prognosis is dependent on the site, number and volume of lesions, the patients' performance status, age and the activity and extent of extracranial disease. METHODS: English literature articles in PubMed from 1950 to June 2021 were reviewed. Article bibliographies provided further references. CONCLUSIONS: Treatment of brain metastasis patients has moved from considering them as a homogenous population of patients, to individualised treatment. In those brain metastases patients of satisfactory performance status with a solitary lesion, especially one in a non-eloquent/accessible area causing significant mass effect and/or raised intracranial pressure or for whom the diagnosis is in doubt (histology needed), surgical resection is usually the treatment of choice. For multiple brain metastases, radiotherapy with or without systemic therapies are usually employed. For relatively fit patients with limited numbers of brain metastases (e.g., 4 or less), stereotactic radiosurgery is standard of care. Current clinical trials are testing the efficacy of stereotactic treatment alone for >4 brain metastases (although it is increasingly used for such patients in many centres) as well as integration of local therapies with targeted and immunological therapies in appropriately selected cases. In certain circumstances, cranial irradiation can be omitted.

Radiation recall reactions: An oncologic enigma.

Radiation recall reactions (RRR) are uncommon but are a well-known phenomenon to oncologists. Tissue damage in a prior irradiation portal is 'recalled' after the administration of a drug, historically cytotoxics, or more recently, targeted or immunotherapeutic agents. Even COVID-19 vaccines are a reported cause. RRR are enigmatic in that their cause is unknown, but they generally have the histopathological and clinical features of acute or chronic inflammation. They can occur in a variety of tissues, the commonest being skin, which accounts for two-thirds of reported cases. They are generally relatively mild and self-limiting once the trigger drug is stopped, although severe cases with tissue necrosis have occurred. Rechallenge with drug does not necessarily cause reactivation of the reaction. Symptomatic treatment with steroids and antihistamines are usually effective, but their impact on the clinical course is unclear. Various hypotheses have been proposed as to the mechanism of RRR; a non-immune fixed drug reaction-like condition, dysregulated release of reactive oxygen species, abnormalities of tissue vasculature and impaired DNA repair. All could lead to a characteristic inflammatory microenvironment, resulting in dysfunction of tissue stem cells, keratinocyte necrosis and dermal abnormalities. Alternatively or in addition, low levels of inflammatory tissue cytokines induced by previous irradiation might be further upregulated by drug exposure. Most information in this review refers to data derived from cutaneous RRR, since they are the most common form reported.