Cue-Reactive Phenomenology Mediates the Relationship Between Positive Schizotypy and Cue-Reactive Urge to Gamble in Poker-Machine Gamblers.

Although ubiquitous in numerous nightlife cultures, poker-machines present a high risk for problematic use and addiction. Previous research has demonstrated that gambling cues (e.g., flashing lights) can activate gambling urges in poker-machine gamblers. However, the processes that contribute to the maintenance of cue-reactive urges to gamble remain unclear. Consequently, the present study explored whether positive schizotypy predicted gambling urge, and whether cue-reactive altered state of awareness, cue-reactive altered time sense, and cue-reactive absorption mediated this relationship. Seventy adults aged between 19 and 68 (M = 48.86, SD = 12.82) participated in an online cue-reactivity experiment. Participants first completed the Problem Gambling Severity Index and the Unusual Experiences subscale of the Short Oxford-Liverpool Inventory of Feelings and Experiences. Subsequently, at three time points (i.e., baseline, directly after a neutral cue, and directly after a gambling cue) participants completed the Altered State of Awareness, Altered Time Sense, and Absorption subscales of the Phenomenology of Consciousness Inventory and a visual analogue scale measuring cue-reactive urge to gamble. It was found that positive schizotypy was significantly positively correlated with cue-reactive urge to gamble. Additionally, cue-reactive altered state of awareness, cue-reactive altered time sense, and cue-reactive absorption mediated this relationship. The theoretical, clinical and practical implications are discussed.

Barriers to Clinical Trial Implementation Among Community Care Centers.

Importance: While an overwhelming majority of patients diagnosed with cancer express willingness to participate in clinical trials, only a fraction will enroll onto a research protocol. Objective: To identify critical barriers to trial enrollment to translate findings into actionable practice changes that increase cancer clinical trial enrollment. Design, Setting, and Participants: This survey study included designated site contacts at oncology practices with teams who were highly involved with the Association of Community Cancer Centers (ACCC) Community Oncology Research Institute (ACORI) clinical trials activities, all American Society of Clinical Oncology (ASCO)-ACCC collaboration pilot sites, and/or sites providing care to at least 25% African American and Hispanic residents. To determine participation trends among health care practices in oncology-focused research, identify barriers to clinical trial implementation and operation, and establish unmet needs for cancer clinics interested in trial participation, a 34-question survey was designed. Survey questions were defined within 3 categories: cancer center demographic characteristics, clinical trial characteristics, and referral practices. The survey was distributed through email and was open from June 20 through October 5, 2022. Main Outcomes and Measures: Participation in and barriers to conducting oncology trials in different community oncology settings. Results: The survey was distributed to 100 cancer centers, with completion by 58 centers (58%) across 25 states. Fifty-two centers (88%) reported that they conduct therapeutic clinical trials, of which 33 (63%) were from urban settings, 11 (21%) were from suburban settings, and 8 (15%) were from rural settings. Only 25% of rural practices (2 of 8) offered phase 1 trials, compared with 67% of urban practices (22 of 33) (P = .01). Respondents noted challenges in conducting research, including patient recruitment (27 respondents [52%]), limited staffing (27 [52%]), and nonrelevant trials for their patient population (25 [48%]). Among sites not offering therapeutic trials, barriers to research conduct included limited infrastructure, funding, and staffing. Most centers (46 of 58 [79%]) referred patients to outside centers for clinical trial enrollment, particularly in the context of late-stage disease and/or disease progression. Only 17 of these sites (37%) had established protocols for patient follow-up subsequent to outside referral. Conclusions and Relevance: In this national survey study of barriers to clinical trial implementation, most sites offered therapeutic trials, but there were significant disparities in trial availability across care settings. Furthermore, fundamental deficiencies in trial support infrastructure limited research activity, including within programs currently conducting research as well as at sites interested in future clinical research opportunities. These results identify crucial unmet needs for oncology clinics to effectively offer clinical trials to patients seeking care.

Development and validation of the Informal Supporter Readiness Inventory (ISRI).

OBJECTIVE: This article outlines the development and validation of the Informal Supporter Readiness Inventory (ISRI), based on the model developed by the present authors in (Davies, 2023). This scale assesses the readiness of informal supporters to intervene or provide support in situations of intimate partner violence (IPV). METHODS: The research followed a three-phased procedure of item development, scale development, and scale evaluation; adhering to best practice guidelines for psychometric development and validation. This process provided empirical substantiation for the domains of the Model of Informal Supporter Readiness (Davies, 2023). RESULTS: The 57-item ISRI incorporates four primary factors: normative, individual, goodman-emotional, and situational-assessment. These factors demonstrated robust internal consistency and factor structures. Additionally, the ISRI evidenced strong test-retest reliability, and both convergent and divergent validity. Although aligning closely with the Model of Informal Supporter Readiness, the scale revealed a nuanced bifurcation of situational factors into situational-emotional and situational-assessment. DISCUSSION: The ISRI offers an important advancement in IPV research by highlighting the multifaceted nature of informal supporter intervention. The findings have several implications, from tailoring individualised supportive interventions to strengthening support networks and empowering survivors. The present study's findings underscore the potential of adopting a social network-oriented approach to interventions in IPV scenarios. Applications for research and practice are discussed.

Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy.

OBJECTIVES: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. METHODS: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. RESULTS: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. CONCLUSION: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.

Distress and psychosocial support seeking: A comparison of rural and metropolitan oncology patient experiences.

INTRODUCTION: Prevalence of distress in cancer patients is established at approximately 50%, yet uptake of psychosocial support is minimal. OBJECTIVE: This study aimed to understand why clinically distressed oncology patients choose not to access psychosocial support, including whether this differs by geographic location. It also aimed to determine the proportion of rural and metropolitan patients experiencing clinical levels of distress, and of these, the proportion who do not wish to access support. DESIGN: The study used a cross-sectional design. Two hundred and ninety-eight Australian cancer patients completed an online survey, including the Distress Thermometer and open-ended questions about reasons for declining support. Descriptive statistics and content analysis were used to analyse the data. FINDINGS: More than half (56%) of participants reported experiencing clinically significant levels of distress. Of these, almost half (47%) declined psychosocial support. Content analysis of reasons for declining psychosocial support resulted in six main concepts: I don't need support; I'm using personal resources to cope; negative perceptions and attitudes; life doesn't stop for cancer; I'm focussed on fighting cancer; and systemic barriers. Rural cancer patients most often indicated using personal resources to cope, while metropolitan participants most commonly indicated not needing support. A range of subconcepts were also identified. Perceiving distress as manageable or transient was almost exclusively reported by metropolitan participants, while stigma was almost exclusively reported by rural participants. DISCUSSION: The findings provided greater depth of insight into reasons cancer patients decline psychosocial support and identified several qualitative differences in the reasons provided by metropolitan and rural patients. Recommendations are provided for clinicians, in particular for clinicians who work with rural cancer patients and their supporters. CONCLUSION: These findings can inform equitable resourcing of psychosocial support in rural areas and the adaptation of psychosocial interventions to be more flexible and responsive to individual needs. This may help increase patient uptake of support, particularly in rural areas.

Bioinformatic Analysis of Recurrent Genomic Alterations and Corresponding Pathway Alterations in Ewing Sarcoma.

Ewing Sarcoma (ES) is an aggressive, mesenchymal malignancy associated with a poor prognosis in the recurrent or metastatic setting with an estimated overall survival (OS) of <30% at 5 years. ES is characterized by a balanced, reciprocal chromosomal translocation involving the EWSR1 RNA-binding protein and ETS transcription factor gene (EWS-FLI being the most common). Interestingly, murine ES models have failed to produce tumors phenotypically representative of ES. Genomic alterations (GA) in ES are infrequent and may work synergistically with EWS-ETS translocations to promote oncogenesis. Aberrations in fibroblast growth factor receptor (FGFR4), a receptor tyrosine kinase (RTK) have been shown to contribute to carcinogenesis. Mouse embryonic fibroblasts (MEFs) derived from knock-in strain of homologous Fgfr4G385R mice display a transformed phenotype with enhanced TGF-induced mammary carcinogenesis. The association between the FGFRG388R SNV in high-grade soft tissue sarcomas has previously been demonstrated conferring a statistically significant association with poorer OS. How the FGFR4G388R SNV specifically relates to ES has not previously been delineated. To further define the genomic landscape and corresponding pathway alterations in ES, comprehensive genomic profiling (CGP) was performed on the tumors of 189 ES patients. The FGFR4G388R SNV was identified in a significant proportion of the evaluable cases (n = 97, 51%). In line with previous analyses, TP53 (n = 36, 19%), CDK2NA/B (n = 33, 17%), and STAG2 (n = 22, 11.6%) represented the most frequent alterations in our cohort. Co-occurrence of CDK2NA and STAG2 alterations was observed (n = 5, 3%). Notably, we identified a higher proportion of TP53 mutations than previously observed. The most frequent pathway alterations affected MAPK (n = 89, 24% of pathological samples), HRR (n = 75, 25%), Notch1 (n = 69, 23%), Histone/Chromatin remodeling (n = 57, 24%), and PI3K (n = 64, 20%). These findings help to further elucidate the genomic landscape of ES with a novel investigation of the FGFR4G388R SNV revealing frequent aberration.

Assessing the relationship between early maladaptive schemas and interpersonal problems using interpersonal scenarios depicting rejection.

BACKGROUND: Early maladaptive schemas (EMSs) have been theorised to contribute to reoccurring interpersonal problems. This study developed a novel experimental paradigm that aimed to assess if EMSs moderate the impact of interpersonal situations on interpersonal responses by manipulating the degree of rejection in a series of interpersonal vignettes depicting acceptance, ambiguous rejection and rejection. METHOD: In a sample of 158 first-year psychology students (27.2% male; 72.2% female; 0.6% other) participant responses to interpersonal scenarios were measured including degree of perceived rejection, emotional distress, conviction in varying cognitive appraisals consistent with attribution theory and behavioural responses to scenarios. Qualitative data was analysed using inductive content analysis and statistical analyses were conducted using multi-level mixed effect linear and logistic regression models using the software Jamovi. RESULTS: People reporting higher EMSs reported increased emotional distress (F(1, 156) = 24.85, p < .001), perceptions of rejection (F(1, 156) = 34.33, p < .001), self-blame (F(1, 156) = 53.25, p < .001), other-blame (F(1, 156) = 13.16, p < .001) and more intentional (F(1, 156) = 9.24, p = .003), stable (F(1, 156) = 25.22, p < .001) and global (F(1, 156) = 19.55, p < .001) attributions but no differences in reported behavioural responses. The results also supported that EMSs moderate the relationship between interpersonal rejection and perceptions of rejection (F(2, 1252) = 18.43, p < .001), emotional distress (F(2, 1252) = 12.64, p < .001) and self-blame (F(2, 1252) = 14.00, p < .001). CONCLUSION: Together these findings suggest that people with EMSs experience increased distress and select negative cognitions in situations where there are higher levels of rejection but that distress and negative cognitions are generally higher in people with EMSs irrespective of the situation.

Role of immunotherapy in chondrosarcoma: A case report and review of the literature.

Chondrosarcomas (CSs) consist of a heterogenous group of primary bone cancers arising from malignant cells which produce cartilaginous matrix. As the second most common primary bone cancer, CS are often resistant to systemic chemotherapy due to poor vascularization, slow proliferation, and expression of multidrug-resistant pumps. Immune checkpoint inhibitors have transformed the field of oncology and are now designated as frontline therapy for many solid tumor cancers. Several studies have demonstrated increased expression of programed cell death 1 (PD-1) and PD-L1 in CS tissue in vitro, which has led to the development of multiple clinical trials for immunotherapy in patients with aggressive CS. In this review, we highlight the ongoing investigation into the role for immunotherapy in CS. We also report the case of a 44-year-old female with a history of stage IV primary CS of the right shoulder who underwent radical resection with recurrence and demonstrated a spectacular sustained response to pembrolizumab at our center. Our review highlights the need for further studies investigating the role of immunotherapy in the treatment of aggressive bone sarcomas that are resistant to standard surgical resection, chemotherapy, and radiation treatment.

Chondrosarcoma is a cancer of the cells that make cartilage and is often removed surgically. However, when the cancer spreads to other organs such as the lungs or are in areas unreachable by surgeons, there are not many effective treatments. While targeted treatments are in development, many of them have unclear effectiveness. A new and rapidly growing area of cancer treatment is known as immunotherapy, which uses the body's own immune system to kill cancer cells. In this review, we discuss trials in using immunotherapy against aggressive forms of chondrosarcoma. We also present the case of a patient where an immunotherapy agent called pembrolizumab was highly effective in preventing disease progression.

Stereotactic Body Radiation Therapy for Oligoprogressive and Oligorecurrent Non-Small-Cell Lung Cancer.

BACKGROUND AND PURPOSE: The role of stereotactic body radiation therapy (SBRT) in oligoprogressive non-small-cell lung cancer (NSCLC) is controversial. We evaluated whether SBRT in a subset of patients with oligoprogressive or oligorecurrent NSCLC offers a durable response, obviating the need to change systemic therapy. METHODS: A retrospective analysis of 168 NSCLC patients who underwent SBRT for oligoprogressive or oligorecurrent disease was performed. Oligoprogression was defined as progression in ≤5 lesions during or after systemic therapy following an initial complete or partial response. Oligorecurrence was defined as progression while off systemic therapy. Progression-free survival (PFS), overall survival (OS) and time to next treatment or death (TNT-D) were estimated. RESULTS: Median age was 68 years. Sixty-seven percent of patients were on systemic therapy at the time of progression. Progression at the primary site was present in 31% of the patients. The number of sites of metastatic progression was 0 to 2 in 76% and 3 to 5 in 24% of the patients. Two-year OS and PFS were 56% (95%CI 46%-64%) and 14% (95%CI 8%-21%), respectively. Median TNT-D was 9 months (95%CI 6-11). No grade 4 or 5 toxicity was seen. In multivariable analysis, patients with 3 to 5 sites of metastatic progression had worse OS (HR 2.6, 95%CI 1.5-4.3, P < .001) and shorter TNT-D (HR 1.7, 95%CI 1.1-2.5, P = .01) than those with 0 to 2 sites. CONCLUSION: SBRT is a safe and viable treatment option for oligoprogressive and oligorecurrent NSCLC. Patients with 0 to 2 sites had better OS and longer TNT-D compared to those with 3 to 5 lesions.

Real-World Outcomes of Latinx Versus Non-Latinx Patients Treated With First-Line Immunotherapy for Metastatic Renal-Cell Carcinoma.

BACKGROUND: There are limited data regarding the impact of ethnicity among patients receiving immune checkpoint inhibitors. We evaluated real-world outcomes between Latinx and non-Latinx patients with metastatic renal-cell carcinoma (mRCC) treated with first-line nivolumab/ipilimumab within 2 different healthcare settings. METHODS: We performed a retrospective analysis of patients with mRCC who received nivolumab/ipilimumab within the Los Angeles County Department of Health Services (LAC-DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between January 1, 2015 and December 31, 2021. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method and covariates were adjusted using multivariate Cox proportional hazards regression. RESULTS: Of 94 patients, 40 patients (43%) were Latinx while the remainder were non-Latinx (44 pts [46%] White, 7 pts [7%] Asian, and 3 pts [3%] Other). Fifty (53%) and 44 (47%) patients received their care at COH and LAC-DHS, respectively. Most Latinx patients (95%) were treated at LAC-DHS, and most non-Latinx patients (89%) were treated at COH. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs. 25.2 months, hazard ratios [HR] 3.61, 95% CI 1.96-6.66, P ≤ .01). Multivariate analysis revealed a HR of 3.41 (95% CI 1.31-8.84; P = .01). At a median follow-up of 11.0 months, the median OS was not reached in either arm at the time of data cutoff. CONCLUSION: Latinx patients with mRCC had a shorter PFS treated with frontline nivolumab/ipilimumab compared to their non-Latinx counterparts. No difference was observed in OS although these data were immature. Larger studies are needed to further interrogate the social and economic determinants of ethnicity on clinical outcomes in mRCC.

Examining Exclusion Criteria in Advanced Prostate Cancer Clinical Trials: An Assessment of recommendations From the American Society Of Clinical Oncology and Friends of Cancer Research.

PURPOSE: Eligibility criteria illustrate the characteristics of the study population and promote the safety of participants. However, overreliance on restrictive eligibility criteria may limit the generalizability of outcomes. As a result, the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) issued statements to curtail these challenges. In this study, we aimed to assess restrictiveness in eligibility criteria across advanced prostate cancer clinical trials. MATERIALS AND METHODS: We identified all phase I, II, and III advanced prostate cancer clinical trials between June 30, 2012, and June 30, 2022, through Clinicaltrials.gov. We evaluated whether a clinical trial excluded, conditionally included, or did not report 4 common criteria: brain metastases, prior or concurrent malignancies, HIV infection, and hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. Performance status (PS) criteria were recorded based on the Eastern Cooperative Oncology Group (ECOG) scale. RESULTS: Out of 699 clinical trials within our search strategy, 265 (37.9%) trials possessed all the required data and were included in our analysis. The most common excluded condition of our interest was brain metastases (60.8%), followed by HIV positivity (46.4%), HBV/HCV positivity (46.0%), and concurrent malignancies (15.5%). Additionally, 50.9% of clinical trials only included patients with ECOG PS 0 to 1. HIV and HBV/HCV infection were exclusion criteria of 22 (80.8%) and 19 (73.1%) immunotherapy trials, respectively. CONCLUSION: Patients with brain metastases, prior or concurrent malignancies, HIV infection, HBV/HCV infection, or low-functioning PS were overly restricted from participating in advanced prostate clinical trials. Advocating for broader criteria may ameliorate generalizability.

Managing Metastatic Renal Cell Carcinoma after Progression on Immunotherapy.

Treatment of metastatic renal cell carcinoma (mRCC) after first-line immune checkpoint inhibitors (ICIs) lacks standardization, with limited evidence from small trials and retrospective data. Vascular endothelial growth factor receptor (VEGFR) inhibition through tyrosine kinase inhibitors (TKIs) is the most widely adopted second-line treatment. Encouraging results have been seen with VEGFR-TKIs in the second-line after exposure to an ICI-based combination, achieving a response rate of 30%, and 75% of patients achieving disease control. Rechallenge with ICI alone seems safe but has limited clinical benefit. Promising regimens with combination therapies and novel drugs are being evaluated in phase 3 trials.

A systematic review of informal supporters of intimate partner violence survivors: the intimate partner violence model of informal supporter readiness.

Background: Intimate partner violence (IPV) is a serious public health issue that consists of physical, sexual, and psychological violence perpetrated by a current or former partner. Informal supporters (e.g., family and friends) of survivors are more often witness to IPV or are the first people a survivor will disclose abuse to and are more able to provide consistent ongoing support than professional services. Therefore, greater understanding of informal supporters is warranted to aid in reducing the risks experienced by survivors. This systematic review aimed to: (1) identify factors associated with either an increase or decrease in helping behaviour toward a survivor, (2), identify the most effective self-care strategies employed by informal supporters, and (3) consider the current theoretical approaches used to understand informal supporters help-giving behavioural intention. Methods: A systematic literature search was conducted following the PRISMA guidelines. The search included English language articles published between 2005 and 2021 in the databases Psych Articles, Scopus, Proquest Social Services Abstracts, and Ebscohost. Studies were included if the primary research aims explored the motivators and inhibitors of helping intention or self-care strategies of adult social network members of adult IPV survivors. Two reviewers independently screened all identified articles for inclusion suitability. Results: One hundred and twenty articles were subjected to full text screening resulting in 31 articles being identified as meeting inclusion criteria. Synthesis of the findings identified the following three key areas associated with help-giving behavioural intentions: normative factors, individual factors, and situational factors. There were no articles identified that considered self-care of informal supporters. Of the 31 articles, 22 had a theoretical underpinning. None of the utilised theories explained all three of the identified factors of help-giving behavioural intention. Conclusion: These results are integrated into a proposed Intimate Partner Violence Model of Informal Supporter Readiness (IPV-MISR), incorporating the identified factors associated with help-giving behavioural intention. This model provides a framework for conceptualising the readiness of an informal supporter to provide adequate support to IPV survivors. The model extends existing theoretical standpoints and has utility in both practice and research.

Twelve-Month Follow-up of the Immune Response After COVID-19 Vaccination in Patients with Genitourinary Cancers: A Prospective Cohort Analysis.

BACKGROUND: Vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have had a transformative impact on morbidity and mortality. However, the long-term impact of vaccination on patients with genitourinary cancers is currently unknown. MATERIALS AND METHODS: This study aimed to assess seroconversion rates in patients with genitourinary cancers receiving COVID-19 vaccination. Patients with prostate cancer, renal cell carcinoma, or urothelial cancer who had not been vaccinated for COVID-19 were included. Blood samples were obtained at baseline and after 2, 6, and 12 months of one dose of an FDA-approved COVID-19 vaccine. Antibody titer analysis was performed using the SCoV-2 Detect IgG ELISA assay, and the results were reported as immune status ratio (ISR). A paired t-test was used for comparison of ISR values between timepoints. In addition, T-cell receptor (TCR) sequencing was performed to assess for differences in TCR repertoire 2 months after vaccination. RESULTS: Out of 133 patients enrolled, 98 baseline blood samples were collected. At 2-, 6-, and 12-month time points 98, 70, and 50 samples were collected, respectively. Median age was 67 (IQR, 62-75), with the majority of patients diagnosed with prostate (55.1%) or renal cell carcinoma (41.8%). Compared to baseline (0.24 [95% CI, 0.19-0.31]) a significant increase in the geometric mean ISR values was observed at the 2-month timepoint (5.59 [4.76-6.55]) (P < .001). However, at the 6-month timepoint, a significant decrease in the ISR values was observed (4.66 [95% CI, 4.04-5.38]; P < .0001). Notably, at the 12-month timepoint, the addition of a booster dose resulted in an absolute increase in the ISR values compared to those who did not receive a booster dose (P = .04). CONCLUSIONS: Only a minority of patients with genitourinary cancers did not ultimately achieve satisfactory seroconversion after receiving commercial COVID-19 vaccination. Cancer type or treatment rendered did not appear to affect the immune response mounted after vaccination.

A Closer Look at EGFR Inhibitor Resistance in Non-Small Cell Lung Cancer through the Lens of Precision Medicine.

The development of EGFR small-molecule inhibitors has provided significant benefit for the affected patient population. Unfortunately, current inhibitors are no curative therapy, and their development has been driven by on-target mutations that interfere with binding and thus inhibitory activity. Genomic studies have revealed that, in addition to these on-target mutations, there are also multiple off-target mechanisms of EGFR inhibitor resistance and novel therapeutics that can overcome these challenges are sought. Resistance to competitive 1st-generation and covalent 2nd- and 3rd-generation EGFR inhibitors is overall more complex than initially thought, and novel 4th-generation allosteric inhibitors are expected to suffer from a similar fate. Additional nongenetic mechanisms of resistance are significant and can include up to 50% of the escape pathways. These potential targets have gained recent interest and are usually not part of cancer panels that look for alterations in resistant patient specimen. We discuss the duality between genetic and nongenetic EGFR inhibitor drug resistance and summarize current team medicine approaches, wherein clinical developments, hand in hand with drug development research, drive potential opportunities for combination therapy.

Systemic Therapy for Chondrosarcoma.

OPINION STATEMENT: Clinical trial enrollment should be actively encouraged in all patients diagnosed with advanced, surgically unresectable chondrosarcoma (CS) due to the lack of consensus treatment recommendations. In the absence of an appropriate clinical trial, treatments are determined based on histologic subtype of CS with consideration given to targetable mutations (i.e., IDH1). Conventional CS is inherently resistant to cytotoxic chemotherapy and patients may benefit from antiangiogenic therapy including off-label use of pazopanib. Individuals harboring an IDH1 mutation may derive clinical benefit from ivosidenib, an IDH1 inhibitor. Upon progression and with functional status permitting, alternative options include mTOR inhibitors (sirolimus, temsirolimus) or other tyrosine kinase inhibitors (dasatinib), though no clear sequencing data exists. For dedifferentiated CS, conventional chemotherapies with osteosarcoma-like regimens are upfront options although prospective data is limited with minimal overall benefit. Alternative treatment options include immunotherapy with pembrolizumab or ivosidenib in IDH1-mutant, dedifferentiated CS, but questionable efficacy was observed in small sample sizes with either approach. In mesenchymal CS, treatment with Ewing sarcoma-like chemotherapy regimens may be considered, although data supporting its use is even more limited given its rarity.

Myelodysplastic syndrome in a 30-year-old man with coronavirus disease 2019 (COVID-19): a diagnostic challenge.

BACKGROUND: Myelodysplastic syndromes (MDS) mainly occur in the elderly but can rarely affect younger individuals too. The correct diagnosis relies on careful morphologic evaluation, cytogenetic/molecular results, and excluding reactive conditions mimicking MDS. We present the clinical, pathologic, cytogenetic, and molecular features of a case of MDS with excess blasts-2 (MDS-EB-2) in a 30-year-old male who was found to have pancytopenia during his hospitalization for coronavirus disease 2019 (COVID-19) and discuss the diagnostic challenges of MDS in patients with COVID-19. CASE PRESENTATION: A 30-year-old man presented to an outside hospital with fever, chills, weakness, coughing spells, dizziness and shortness of breath and was diagnosed with bilateral pneumonia due to COVID-19. At the outside hospital, he was found to be pancytopenic, and a subsequent bone marrow aspiration and biopsy raised concern for a COVID-19 induced hemophagocytic lymphohistiocytosis. In addition, MDS could not be ruled out. The patient was thus referred to our institute for further management. The patient's peripheral blood showed pancytopenia with occasional dysplastic neutrophils and a few teardrop cells. Given the diagnostic uncertainty, a bone marrow aspiration and a biopsy were repeated revealing a hypercellular bone marrow with erythroid hyperplasia, megakaryocytic hyperplasia, trilineage dysplasia, increased blasts (13%), many ring sideroblasts, and mild to moderate myelofibrosis, consistent with MDS-EB-2. Chromosomal analysis revealed isochromosome 14. Next generation sequencing demonstrated SF3B1 K700E mutation. DISCUSSION AND CONCLUSION: The diagnosis of MDS can be challenging, particularly in young patients. Cytopenia and myelodysplastic features have been reported in COVID-19 patients, making the diagnosis of MDS more elusive. A careful pathologic examination of the bone marrow with ancillary studies including flow cytometry, immunohistochemistry, and cytogenetic and molecular studies in combination with a thorough clinical evaluation, leads to the accurate diagnosis.

Attachment style, thought suppression, self-compassion and depression: Testing a serial mediation model.

Attachment anxiety has been consistently linked with increased vulnerability to depression, and hyperactivating emotion regulation strategies (e.g., rumination) have been shown to mediate this relationship. Investigations of mediators of the attachment avoidance to depression relationship have yielded inconsistent findings, and the nature of this relationship remains to be clarified. There is evidence to suggest that the constructs of thought suppression and self-compassion are associated with attachment avoidance and also with depressive symptomology. In order to further clarify the nature of this relationship, the present study tested a serial mediation model, whereby it was hypothesised that thought suppression and self-compassion were serial mediators of the relationship between attachment avoidance and depression. One hundred and forty-eight participants completed an online composite questionnaire consisting of the Experiences in Close Relationships-Revised Questionnaire, the White Bear Suppression Inventory, the Self-Compassion Scale, and the Depression Anxiety and Stress Scale-21. Initial results supported the hypothesised serial mediation model (Model A); that is, higher attachment avoidance predicted higher thought suppression, higher thought suppression predicted lower levels of self-compassion and lower levels of self-compassion predicted higher depression. However, this model was no longer significant following the inclusion of attachment anxiety as a covariate within the post-hoc analysis. A second, post-hoc serial mediation model was tested (Model B), with the only difference being that attachment anxiety replaced attachment avoidance as the independent variable. This model was significant, with and without the inclusion of attachment avoidance as a covariate. The study provides evidence for the central role of thought suppression and self-compassion as mechanisms underlying the relationship between insecure attachment and depression, and indicates that these factors operate in opposing directions. The findings are discussed in terms of explicating some of the processes through which insecure attachment confers vulnerability to depression. The implications of the observed degree of shared variance between the two attachment dimensions suggests these constructs may be more appropriately considered overlapping, rather than orthogonal.