XR and mental wellbeing: state of the art and future research directions for the Metaverse.

Introduction: The purpose of this study is to provide an overview of extant research regarding XR technology and its effect on consumer wellbeing. With the hopes of informing marketing practitioners on XR consumer psychology, in preparation for the Metaverse. Methods: To achieve the above aim, two types of analysis took place. Firstly, a bibliometric analysis was conducted which was then followed by a framework-based structured literature review. The latter entailed an analysis of 81 articles evaluated from a positive psychological approach. Findings: Following the TCCM framework, the analysis revealed the most common psychological theories demonstrating potential avenues for XR to impact consumer wellbeing. Moreover, researchers found preliminary links between, theory, characteristics, and contexts. Giving a preliminary description of how theory manifests into reality. Finally, the overview of extant literature was used to propose new avenues for future research pertaining to marketing, the Metaverse, and consumer effects. Conclusion: In conclusion, the paper provides stakeholder insights which can ensure minimal consumer risk and sustainable use of the XR technology and Metaverse. While addressing the need for more research that uncovers the psychological effects of emerging technologies, so to prepare for the Metaverse. This is especially important when considering the current upsurge of these technologies and the uncertainties associated with their novelty and the idea of an 'always on' consumer.

Influenza burden averted with a cell-based quadrivalent seasonal influenza vaccine compared with egg-based quadrivalent seasonal influenza vaccine.

BACKGROUND: Cell-based quadrivalent inactivated influenza vaccines (IIV4c) avoid egg-adaptive mutations found in egg-based production, improving vaccine effectiveness (VE). Studies demonstrate improved VE for IIV4c relative to egg-based quadrivalent inactivated influenza vaccines (IIV4). RESEARCH DESIGN AND METHODS: We built on a static compartmental model developed by the CDC to estimate the influenza burden in persons 0-64 years that would be additionally averted by vaccination with IIV4c vs. IIV4. Model inputs were based on published data from 2017-2018, 2018-2019, and 2019-2020 Northern Hemisphere influenza seasons for the US. RESULTS: Over 3 influenza seasons, relative to IIV4, IIV4c would avert 31-39% more symptomatic cases, 29-40% more outpatient visits, 29-38% more hospitalizations and ICU admissions, and 34-49% more deaths vs. IIV4. In a deterministic sensitivity analysis, the main drivers were the relative VE of IIV4c vs. IIV4 in the 2017-2018 season and influenza burden estimates for the 2018-2019 and 2019-2020 seasons. Probabilistic sensitivity analysis showed that the interquartile range of symptomatic cases was ± 13% of baseline in 2017-2018, ±8% in 2018-2019, and ± 7% in 2019-2020. CONCLUSIONS: IIV4c prevented significantly more symptomatic cases, outpatient visits, hospitalizations, and deaths than IIV4 in persons aged 0-64 years over 3 influenza seasons.

Quantification of Right Ventricular Amyloid Burden with 18F-florbetapir PET/CT and its Association with Right Ventricular Dysfunction and Outcomes in Light-Chain Amyloidosis.

AIMS: In systemic light-chain (AL) amyloidosis, quantification of right ventricular (RV) amyloid burden has been limited and the pathogenesis of RV dysfunction is poorly understood. Using 18F-florbetapir positron emission tomography/computed tomography (PET/CT), we aimed to quantify RV amyloid, correlate RV amyloid with RV structure and function, determine the independent contributions of RV, left ventricular (LV) and lung amyloid to RV function, and to associate RV amyloid with major adverse cardiac events (MACE: death, heart failure hospitalization, cardiac transplantation). METHODS AND RESULTS: We prospectively enrolled 106 participants with AL amyloidosis (median age 62 years, 55% males) who underwent 18F-florbetapir PET/CT, magnetic resonance imaging and echocardiography. 18F-florbetapir PET/CT identified RV amyloid in 63% of those with, and 40% of those without cardiac involvement by conventional criteria. RV amyloid burden correlated with RV ejection fraction (EF), RV free wall longitudinal strain (FWLS), RV wall thickness, RV mass index, NT-proBNP, troponin T, LV amyloid and lung amyloid (each p<0.001). In multivariable analysis, RV amyloid burden, but not LV or lung amyloid burden, predicted RV dysfunction (EF p=0.014; FWLS p<0.001). During a median follow-up of 28 months, RV amyloid burden predicted MACE (p<0.001). CONCLUSIONS: This study shows for the first time that 18F-florbetapir PET/CT identifies early RV amyloid in systemic AL amyloidosis prior to alterations in RV structure and function. Increasing RV amyloid on 18F-florbetapir PET/CT is associated with worse RV structure and function, predicts RV dysfunction and predicts MACE. These results imply a central role for RV amyloid in the pathogenesis of RV dysfunction.

Incidence of Squamous Cell Carcinoma in Situ Upstaged to Invasive Squamous Cell Carcinoma During Mohs Surgery.

Objective: We sought to record the incidence and risk factors associated with upstaging squamous cell carcinoma in situ (SCCIS) to squamous cell carcinoma (SCC) during Mohs surgery with the largest sample size to date. Methods: Patient records of preoperative biopsy-proven SCCIS being treated with Mohs between January 2019 to March 2022 were identified and reviewed. Postoperative diagnoses of invasive SCC proven by dermal infiltration on pathology were identified as upstaged SCCIS. Results: From 2,043 cases of preoperative diagnosed SCCIS, 47 (2.3%) were upstaged to SCC during Mohs surgery. Of the 47 invasive tumors, a large proportion on the hands (29.8%) and lesions with larger preoperative sizes had a higher risk of being upstaged to invasive SCC in this study. Limitations: All of the patients included were from rural and suburban areas of North Carolina. The only sections obtained were those reviewed for margin analysis, which may significantly underestimate the actual number of invasive SCC, as only the deepest and furthest portions were examined. Conclusion: This retrospective study concluded that 2.3 percent of preoperatively diagnosed SCCIS were upstaged to SCC during treatment with Mohs surgery. Large lesions (>2cm) and lesions on the hand were more likely to be upstaged (29.8%). Treatment must be individualized considering the size of the lesion, the anatomic location, and the possibility that in some cases the initial biopsy may not have been able to accurately distinguish SCCIS from SCC. Although there is a myriad of treatment options for SCC, select patients with increased risk factors for upstaged SCC must be considered for margin assessed treatment modalities.

Myocardial Characterization for Early Diagnosis, Treatment Response Monitoring, and Risk Assessment in Systemic Light-Chain Amyloidosis.

Aims: In systemic light-chain (AL) amyloidosis, cardiac involvement portends poor prognosis. Using myocardial characteristics on magnetic resonance imaging (MRI), this study aimed to detect early myocardial alterations, to analyze temporal changes with plasma cell therapy, and to predict risk of major adverse cardiac events (MACE) in AL amyloidosis. Methods and Results: Participants with recently diagnosed AL amyloidosis were prospectively enrolled. Presence of AL cardiomyopathy (AL-CMP vs. AL-non-CMP) was determined by abnormal cardiac biomarkers. MRI was performed at baseline and 6 months, with 12-month imaging in AL-CMP cohort. MACE was defined as all-cause death, heart failure hospitalization, or cardiac transplantation. Mayo AL stage was based on troponin T, NT-proBNP, and difference in free light chains. The study cohort included 80 participants (median age 62 years, 58% males). Median left ventricular extracellular volume (ECV) was significantly higher in AL-CMP (53% vs. 30%, p<0.001). ECV was abnormal (>32%) in all AL-CMP and in 47% of AL-non-CMP. ECV tended to increase at 6 months and decreased significantly from 6 to 12 months in AL-CMP (median -3%, p=0.011). ECV was strongly associated with MACE (p<0.001), and improved MACE prediction when added to Mayo AL stage (p=0.002). ECV≤32% identified a cohort without MACE, while ECV>48% identified a cohort with 74% MACE. Conclusions: In AL amyloidosis, ECV detects subclinical cardiomyopathy. ECV tends to increase from baseline to 6 months and decreases significantly from 6 and 12 months of plasma cell therapy in AL-CMP. ECV provides excellent risk stratification and offers additional prognostic performance over Mayo AL stage.

Prognostic Value of Left Ventricular 18 F-Florbetapir Uptake in Systemic Light-Chain Amyloidosis.

Background: Myocardial immunoglobulin light-chain (AL) amyloid deposits trigger heart failure, cardiomyocyte stretch and myocardial injury, leading to adverse cardiac outcomes. Positron emission tomography/computed tomography (PET/CT) with 18 F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden, but its prognostic value is not known. Therefore, we aimed to evaluate the prognostic value of LV amyloid burden quantified by 18 F-florbetapir PET/CT and to identify mechanistic pathways mediating its association with outcomes. Methods: Eighty-one participants with newly-diagnosed systemic AL amyloidosis were prospectively enrolled and underwent 18 F-florbetapir PET/CT. LV amyloid burden was quantified using 18 F-florbetapir LV percent injected dose (%ID). Mayo AL stage was determined using troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and difference between involved and uninvolved free light chain levels. Major adverse cardiac events (MACE) were defined as all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months. Results: Among participants (median age 61 years, 57% males), 36% experienced MACE. Incidence of MACE increased across tertiles of LV amyloid burden from 7% to 63% (p<0.001). LV amyloid burden was significantly associated with MACE in univariable analysis (hazard ratio 1.45, 95% confidence interval 1.15-1.82, p=0.002). However, this association became non-significant in multivariable analyses adjusted for Mayo AL stage. Mediation analysis showed that the association between 18 F-florbetapir LV %ID and MACE was primarily mediated by NT-proBNP (p<0.001), a marker of cardiomyocyte stretch and component of Mayo AL stage. Conclusion: In this first study to link cardiac 18 F-florbetapir uptake to subsequent outcomes, LV amyloid burden estimated by LV %ID predicted MACE in AL amyloidosis. But this effect was not independent of Mayo AL stage. LV amyloid burden was associated with MACE primarily via NT-pro-BNP, a marker of cardiomyocyte stretch and component of Mayo AL stage. These findings provide novel insights into the mechanism through which myocardial AL amyloid leads to MACE. Clinical Perspective: In systemic light-chain (AL) amyloidosis, cardiac involvement is the key determinant of adverse outcomes. Usually, prognosis is based on the Mayo AL stage, determined by troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the difference between involved and uninvolved immunoglobulin free light chain levels (dFLC). Cardiac amyloid burden is not considered in this staging. In the present study, we used the amyloid-specific radiotracer 18 F-florbetapir to quantify left ventricular (LV) amyloid burden in 81 participants with newly-diagnosed AL amyloidosis and evaluated its prognostic value on major adverse outcomes (MACE: all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months). We found that higher LV amyloid burden by 18 F-florbetapir positron emission tomography/computed tomography (PET/CT) was strongly associated with MACE. However, this association became non-significant after adjustment for the Mayo AL stage. Mediation analysis offered novel pathophysiological insights, implying that LV amyloid burden leads to MACE predominantly through cardiomyocyte stretch and light chain toxicity (by NT-proBNP), rather than through myocardial injury (by troponin T), also considering the severity of plasma cell dyscrasia (by dFLC). This mediation by NT-proBNP may explain why the association with outcomes was non-significant with adjustment for Mayo AL stage. Together, these results establish quantitative 18 F-florbetapir PET/CT as a valid method to predict adverse outcomes in AL amyloidosis. These results support the use of 18 F-florbetapir PET/CT to measure the effects of novel fibril-depleting therapies, in addition to plasma cell therapy, to improve outcomes in systemic AL amyloidosis.

Point-of-care hemoglobin A1c margin of error alters resident management of Type 2 diabetes when near glycemic target.

AIMS: Point-of-care (POC) HbA1c is frequently used as a surrogate for serum HbA1c. We aimed to determine if resident management of type 2 diabetes changed after accounting for the + 0.5% margin of error associated with POC HbA1c devices. METHODS: Residents were surveyed in an outpatient clinic regarding two of their patients with type 2 diabetes for which they had obtained a POC HbA1c. For one patient, the resident was asked if management would change if the POC HbA1c were 0.5% higher (called the positive case), and for another if management would change if POC HbA1c were 0.5% lower (negative case). RESULTS: Twelve of 58 (21%) cases had a change in management. Of the 27 cases where POC HbA1c was near the glycemic target (defined as POC HbA1c ≥6.0% and <8.0%), 11 (41%) resulted in a change in management while one (3%) of the 31 cases outside that interval had a change in management. CONCLUSION: POC HbA1c testing is well-suited for patients with poorly controlled type 2 diabetes while serum HbA1c testing may be more appropriate when near a patient's personalized HbA1c target since small changes in HbA1c can lead to differences in medical management.

Additional Burden Averted in the United States From Use of MF59-Adjuvanted Seasonal Influenza Vaccine Compared With Standard Seasonal Influenza Vaccine Among Adults ≥65 Years.

Background: The MF59-adjuvanted trivalent inactivated influenza vaccine (aIIV3) is designed to overcome immunosenescence and enhance vaccine responses in older adults. We expanded on the Centers for Disease Control and Prevention (CDC) modeling method to estimate the number of additional influenza-related outcomes averted with aIIV3 versus generic quadrivalent inactivated influenza vaccine (IIV4) in adults ≥65 years over 3 influenza seasons (2017-2018 to 2019-2020) in the United States. Methods: A static compartmental model was developed based on an existing CDC model with 2 previously recommended calculation methods that increased the accuracy of the model in providing estimates of burden averted. Model inputs included vaccine effectiveness, vaccine coverage, population counts, and disease burden estimates. Additional burden averted (symptomatic cases, outpatient visits, hospitalizations, intensive care unit [ICU] admissions, and deaths) was expressed as total incremental cases averted between the vaccines. Sensitivity analyses tested the resilience of the model results to uncertainties in model inputs. Results: The model estimated that vaccination with aIIV3 versus IIV4 would avert 2.24 times as many symptomatic cases, outpatient visits, hospitalizations, ICU stays, and deaths during 2017-2018; the burden averted in 2018-2019 and 2019-2020 with aIIV3 would be 3.44 and 1.72 times that averted with IIV4, respectively. Disease burden estimates and relative vaccine effectiveness of aIIV3 had the greatest impact on model estimates. Conclusions: Over 3 influenza seasons, the model estimated that aIIV3 was more effective than IIV4 in averting influenza-related outcomes, preventing 1.72 to 3.44 times as many influenza illnesses with proportionate decreases in related healthcare use and complications.

Dermatomyositis: a debilitating paraneoplastic phenomenon following a diagnosis of localised squamous cell carcinoma of the cervix.

This case report describes the management of a patient, recently diagnosed with Stage IIIC cervical cancer, presenting with significant proximal muscle weakness, dysphagia and cutaneous changes over the hands, knees and outer thighs bilaterally. Following multiple investigations, this clinical presentation was proven to be dermatomyositis as a paraneoplastic phenomenon, a rare diagnosis with cervical cancer.Improvement of the presenting symptoms followed commencement of radical chemoradiation to the primary tumour plus administration of high dose steroids and intravenous immunoglobulins.As demonstrated in this case, and accompanying literature review, dermatomyositis is a rare complication of cervical cancer but should be considered as urgent treatment of the underlying malignancy is imperative. Involving members of the multidisciplinary team, including dieticians and physiotherapists, is of utmost importance to optimise the patient's recovery from such a debilitating diagnosis.

Beyond the Knife in Renal Cell Carcinoma: A Systematic Review-To Ablate or Not to Ablate?

Intensified systemic therapy in metastatic renal cell carcinoma (mRCC) has led to improved patient outcomes. Patients commonly require local control of one or a few metastases. The aim was to evaluate metastasis-directed ablative therapies in extracranial mRCC. Two databases and one registry were searched, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach, for all prospective and matched-pair case-control mRCC studies of radiofrequency ablation (RFA), cryotherapy, microwave ablation (MWA), and stereotactic body radiotherapy (SBRT). Eighteen studies were identified. Fourteen investigated SBRT in 424 patients. Four thermal ablation studies were identified: two cryotherapy (56 patients) and two RFA studies (90 patients). The median participant number was 30 (range 12-69). The combined median follow-up was 17.3 months (range 8-52). Four SBRT studies reported local control (LC) at 12 months, median 84.4% (range 82.5-93). Seven studies (six SBRT and one cryotherapy) reported an LC rate of median 87% (79-100%). Median overall survival (OS) was reported in eight studies (five SBRT, two cryotherapy, and one RFA) with a median of 22.7 months (range 6.7-not reached). Median progression-free survival was reported in seven studies (five SBRT, one cryotherapy, and one RFA); the median was 9.3 months (range 3.0-22.7 months). Grade ≥ 3 toxicity ranged from 1.7% to 10%. SBRT has excellent local control outcomes and acceptable toxicity. Only four eligible thermal ablative studies were identified and could not be compared with SBRT. Translationally rich definitive studies are warranted.

European Society of Gynaecological Oncology Guidelines for the Management of Patients with Vulvar Cancer - Update 2023.

BACKGROUND: As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer. OBJECTIVE: To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer. METHODS: The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives. RESULTS: The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.

Variance component estimation and genome-wide association of predicted methane production in crossbred beef steers.

Enteric methane is a potent greenhouse gas and represents an escape of energy from the ruminant digestive system. Additive genetic variation in methane production suggests that genetic selection offers an opportunity to diminish enteric methane emissions. Logistic and monetary difficulties in directly measuring methane emissions can make genetic evaluation on an indicator trait such as predicted methane production a more appealing option, and inclusion of genotyping data can result in greater genetic progress. Three predicted methane production traits were calculated for 830 crossbred steers fed in seven groups. The methane prediction equations used included mathematical models from Ellis et al. (2007), Mills et al. (2003), and IPCC (2019). Pearson correlations between the traits were all greater than 0.99, indicating that each prediction equation behaved similarly. Further, the Spearman correlations between the estimated breeding values for each trait were also 0.99, which suggests any of the predicted methane models could be used without substantially changing the ranking of the selection candidates. The heritabilities of Ellis, Mills, and IPCC predicted methane production were 0.60, 0.62, and 0.59, respectively. A genome-wide association study identified one single nucleotide polymorphism (SNP) that reached the threshold for significance for all of the traits on chromosome 7 related to oxidoreductase activity. Additionally, the SNP slightly below the significance threshold indicate genes related to collagen, intracellular microtubules, and DNA transcription may play a role in predicted methane production or its component traits.

Cattle produce methane, a greenhouse gas, as a byproduct of their digestion. It is possible to breed for animals which naturally produce less methane; however, measuring animals for methane production can be difficult or expensive and is required for effective selection. Therefore, an alternative solution is to use a mathematical model to predict methane production and select for animals with low predicted methane. The heritability of predicted methane production from each model ranged from 0.59 to 0.62. Animals were ranked nearly identical, regardless of model used. A genome-wide association study was also conducted to determine what loci may be related to predicted methane production. One significant locus was identified on chromosome 7 related to oxidoreductase activity. Other loci approaching significance showed that genes related to collagen production, intracellular microtubule binding, and DNA transcription may be related to predicted methane production. In particular, collagen turnover may have a relationship to predicted methane because it affects growth rate, which is driven by dry matter intake, which, in turn, is the primary driver of predicted methane production.

Comprehension by Caregivers and Adolescents of Clinical Trial Information Delivered via Multimedia Video Versus Conventional Practice: Nonrandomized Controlled Trial.

BACKGROUND: Research participants often misunderstand the required elements of informed consent information, whether provided in written or oral format. Informed consent instruments with embedded evidence-based learning theory principles administered in multimedia electronic formats may improve comprehension and retention. OBJECTIVE: This study aims to determine whether study information comprehension and retention using an interactive multimedia video consent process was noninferior to comprehension and retention after an in-person face-to-face interaction with a conventional written consent document for caregivers and adolescents enrolled in a clinical trial. METHODS: Participants were caregivers and children aged 12 to 17 years who were enrolled in a clinical trial of asthma treatment. Consent information was presented as a multimedia web-based video consent interaction or as a conventional written consent document with in-person interaction between the prospective participants and the study staff. The trial used a parallel nonrandomized noninferiority design that compared the 2 consent methods. Caregivers and adolescents completed a 17-item open-ended comprehension questionnaire (score range 17-51) at enrollment and at the end of the study 20 weeks later. Comprehension and retention were compared between the consent formats. Noninferiority was established if the 95% CI upper bound of the difference in scores (conventional format minus web-based) was less than the noninferiority margin of 2.4; superiority was established if the upper bound of the CI was <0. RESULTS: In total, 54 caregiver and adolescent dyads completed the interactive multimedia web-based video consent, and 25 dyads completed the conventional consent. Overall, 33% (26/79) of all adolescents were Black, 57% (45/79) were male, and 61% (48/79) had a household income of

Exploring the Darkverse: A Multi-Perspective Analysis of the Negative Societal Impacts of the Metaverse.

The Metaverse has the potential to form the next pervasive computing archetype that can transform many aspects of work and life at a societal level. Despite the many forecasted benefits from the metaverse, its negative outcomes have remained relatively unexplored with the majority of views grounded on logical thoughts derived from prior data points linked with similar technologies, somewhat lacking academic and expert perspective. This study responds to the dark side perspectives through informed and multifaceted narratives provided by invited leading academics and experts from diverse disciplinary backgrounds. The metaverse dark side perspectives covered include: technological and consumer vulnerability, privacy, and diminished reality, human-computer interface, identity theft, invasive advertising, misinformation, propaganda, phishing, financial crimes, terrorist activities, abuse, pornography, social inclusion, mental health, sexual harassment and metaverse-triggered unintended consequences. The paper concludes with a synthesis of common themes, formulating propositions, and presenting implications for practice and policy.

Socioeconomic Factors Associated With a Late-Stage Pancreatic Cancer Diagnosis: An Analysis of the National Cancer Database.

Background Pancreatic adenocarcinoma is an aggressive, lethal cancer. It is the fourth leading cause of cancer death in the United States and is often asymptomatic until later stages. Thus, it is critical to identify patients earlier in their disease course. Socioeconomic factors can assist in determining who is at higher risk of presenting at later stages of the disease. Using the National Cancer Database (NCDB), we aim to identify the associations between socioeconomic factors and the stage of pancreatic cancer at diagnosis. Methodology In this study, 256,822 patients from the NCDB who were diagnosed with pancreatic cancer from 2004 to 2018 at stage 0-I and stage IV were compared based on age, race, sex, ethnicity, insurance type, income, geographic location, education, and Charlson-Deyo score. Demographic factors of patients who presented with early and late-stage disease were compared using the chi-squared test and multivariate logistic regression. Results We identified significant associations between race, sex, insurance status, education, income, and geographic location with the stage of disease at diagnosis. Males were more likely to be diagnosed with late-stage cancer than early-stage (52.8% vs. 47.9%, p < 0.001). Females were more likely to have an earlier-stage diagnosis when compared to males (odds ratio (OR) = 0.857, 95% confidence interval (CI) = 0.839-0.875, p < 0.001). Black patients presented at a later stage when compared to White patients (OR = 1.106, 95% CI = 1.069-1.144, p < 0.001). Private and Medicaid insurance had higher rates of late-stage diagnosis than early stages, and all other types of insurance had lower rates of late-stage diagnosis than patients without insurance (p < 0.001). Patients from a zip code with less than $38,000 median household income and zip codes with lower levels of high school graduation had higher rates of late-stage diagnosis (p < 0.025). Conclusions Factors associated with the increased likelihood of pancreatic cancer presentation at the advanced stage compared to the early stage include multiple minority and traditionally underserved populations. Black race, underinsurance, or residing in low-income or low-education zip codes was significantly associated with presenting at a late stage, which is strongly associated with worse survival outcomes.

Outcomes associated with treatment to all sites of disease in patients with stage IVB cancer of the cervix.

OBJECTIVE: The use of chemoradiation in patients with stage IVB cancer of the cervix was evaluated to determine if definitive treatment offers benefit. METHODS: A database of 546 patients with cancer of the cervix treated between January 2005 and May 2021 at a tertiary academic medical center was reviewed retrospectively to identify patients with stage IVB disease. Log rank test, regression analysis, and the Kaplan-Meier method were used to identify and compare variables and estimate progression free survival and overall survival. RESULTS: Thirty-three patients with stage IVB cervical cancer were identified. Median age was 53 years (range 28-78). Pathology subtypes were squamous cell (n=22, 67%), adenocarcinoma (n=8, 24%), and clear cell (n=3, 9%). Metastases were classified as lymphatic (n=14, 42%) or hematogenous (n=19, 58%). Following treatment to all sites with chemoradiotherapy and selected use of surgery (n=23), six patients (26%, lymphatic n=4, hematogenous n=2) remained disease free for a median duration of 4 years (range 3-17 years). Recurrences in the remaining patients were distant (n=13) or local (n=4). All patients in the chemotherapy group (n=10, 100%) progressed. Kaplan-Meier analysis showed that median progression free survival was longer for patients treated at all disease sites than for patients treated with chemotherapy alone (19 vs 11 months, p=0.01). However, this was not the case for overall survival (49 vs 33 months, p=0.15). Patients with metastases limited to lymph nodes also had longer median progression free survival (22 vs 11 months, p=0.04) but not overall survival (p=0.68). CONCLUSIONS: Patients with stage IVB cancer of the cervix may benefit from treatment to all sites of disease, if feasible and safe, as demonstrated by improved progression free survival.

Targeted Molecular Testing in Endometrial Carcinoma: Validation of a Clinically Driven Selective ProMisE Testing Protocol.

Incorporation of molecular classification into clinicopathologic assessment of endometrial carcinoma (EC) improves risk stratification. Four EC molecular subtypes, as identified by The Cancer Genome Atlas, can be diagnosed through a validated algorithm Pro active M olecular R is k Classifier for E ndometrial Cancer (ProMisE) using p53 and mismatch repair (MMR) protein immunohistochemistry (IHC), and DNA polymerase epsilon ( POLE) mutational testing. Cost and access are major barriers to universal testing, particularly POLE analysis. We assessed a selective ProMisE algorithm (ProMisE-S): p53 and MMR IHC on all EC's with POLE testing restricted to those with abnormal MMR or p53 IHC (to identify POLEmut EC with secondary abnormalities in MMR and/or p53) and those with high-grade or non-endometrioid morphology, stage >IA or presence of lymphovascular space invasion (so as to avoid testing on the lowest risk tumors). We retrospectively compared the known ProMisE molecular classification to ProMisE-S in 912 EC. We defined a group of "very low-risk" EC (G1/G2, endometrioid, MMR-proficient, p53 wild-type, stage IA, no lymphovascular space invasion) in whom POLE testing will not impact on patient care; using ProMisE-S, POLE testing would not be required in 55% of biopsies and 38% of all EC's, after evaluation of the hysterectomy specimen, in a population-based cohort. "Very low-risk" endometrioid EC with unknown POLE status showed excellent clinical outcomes. Fifteen of 166 (9%) of all p53abn EC showed G1/G2 endometrioid morphology, supporting the potential value of universal p53 IHC. The addition of molecular testing changed the risk category in 89/896 (10%) EC's. In routine practice, POLE testing could be further restricted to only those patients in whom this would alter adjuvant therapy recommendations.