Immunotherapy for ovarian cancer is improved by tumor targeted delivery of a neoantigen surrogate.

Ovarian cancer is known for its poor neoantigen expression and strong immunosuppression. Here, we utilized an attenuated non-pathogenic bacterium Listeria monocytogenes to deliver a highly immunogenic Tetanus Toxoid protein (Listeria-TT), as a neoantigen surrogate, into tumor cells through infection in a metastatic mouse ovarian cancer model (Id8p53-/-Luc). Gemcitabine (GEM) was added to reduce immune suppression. Listeria-TT+GEM treatments resulted in tumors expressing TT and reactivation of pre-existing CD4 and CD8 memory T cells to TT (generated early in life). These T cells were then attracted to the TT-expressing tumors now producing perforin and granzyme B. This correlated with a strong reduction in the ovarian tumors and metastases, and a significant improvement of the survival time compared to all control groups. Moreover, two treatment cycles with Listeria-TT+GEM doubled the survival time compared to untreated mice. Checkpoint inhibitors have little effect on ovarian cancer partly because of low neoantigen expression. Here we demonstrated that Listeria-TT+GEM+PD1 was significantly more effective (efficacy and survival) than PD1 or Listeria-TT+GEM alone, and that more treatment cycles with Listeria-TT+GEM+PD1 significantly increased the survival time compared to Listeria-TT+GEM alone. In summary, the results of this study suggest that our approach may benefit ovarian cancer patients.

Direct oral anticoagulant (DOACs) prescribing practices of members of the Society of Gynecologic Oncology and American Society of Clinical Oncology.

BACKGROUND: Cancer associated venous thromboembolism (VTE) is associated with significant morbidity and mortality. Direct oral anticoagulants (DOACs) have emerged as alternatives to injectable medications for both thromboprophylaxis and treatment of VTE. Several recent clinical trials have demonstrated safety and efficacy of DOACs in high risk patients receiving systemic chemotherapy as well as postoperative prophylaxis after surgery for gynecologic cancer. Major consensus guidelines from multiple organizations support the use of DOACs for these indications but prescription practices are not well characterized. METHODS: A survey study was sent concurrently to members of the Society of Gynecologic Oncology (SGO) and American Society of Clinical Oncology (ASCO) Research Survey Pool between May and June of 2021. The study was designed to assess DOAC prescription practices amongst members of these societies who routinely prescribe chemotherapy. Bivariate analyses comparing responses from ASCO participants and SGO participants were compared using chi-squared and Fisher exact tests. RESULTS: A total of 103 physicians were included in the ASCO group and 139 in the SGO group. A majority of participants in both groups reported familiarity with prescribing DOACs (99% of ASCO and 96% of SGO respondents). ASCO respondents were more likely to consider DOACs as first line therapy for treatment of cancer-associated VTE than SGO members (82% vs 63%, p < 0.01) and SGO members were more likely to consider low molecular weight heparin (LMWH) the standard of care treatment (66% vs 25% p < 0.01). Most respondents in both groups (75%) felt DOACs were equally safe and effective compared to LMWH but more ASCO members felt DOACs were cost effective (70% vs 49%, p < 0.01). More SGO respondents reported having prescribed prophylactic anticoagulation during chemotherapy than ASCO members (53% vs 35%, p < 0.01). CONCLUSION: ASCO respondents were more likely to prescribe DOACs for both treatment and prophylaxis of cancer-associated VTE than SGO members. However, SGO members were more likely to prescribe prophylactic anticoagulation to high risk patients initiating chemotherapy compared to ASCO members.

The experience of patients with lung cancer during the COVID-19 pandemic and its importance for post-pandemic outpatient cancer care planning: A cross sectional study exploring the roles of age and frailty.

INTRODUCTION: The COVID-19 pandemic impacted the care and experiences of people with cancer, but it presented an opportunity to improve the delivery of outpatient care post-pandemic. MATERIALS AND METHODS: We performed an observational cross-sectional study with people with lung cancer throughout the COVID-19 pandemic. A survey investigated patients' experiences and preferences regarding the delivery of cancer care to plan for post-pandemic care, as well as the pandemic's impact on their functional status (physical and psycho-social), exploring the role of age and frailty. RESULTS: Amongst 282 eligible participants, 88%, 86%, and 59% of patients reported feeling appropriately supported during the pandemic by their cancer centre, friends/family, and primary care services, respectively. Remote oncology consultations were delivered to 90% of patients during the pandemic, of which 3% did not meet patients' expectations. Regarding post-pandemic outpatient care preferences, face-to-face appointments were preferred by 93% for the first appointment, by 64% when discussing imaging results, and by 60% for reviews during anti-cancer treatments. Older patients aged 70 years and above were more likely to favour face-to-face appointments (p = 0.007), regardless of their frailty status. Patient preferences changed over time, with the more recent participants preferring remote appointments during anti-cancer treatments (p = 0.0278). Regarding the pandemic's impact, abnormal levels of anxiety and depression were found in 16% and 17% of patients, respectively. Younger patients experienced higher abnormal levels of anxiety and depression (p = 0.036, p = 0.021). Amongst the older sub-group, those with frailty had higher levels of anxiety and depression (p < 0.001). Amongst all participants, 54% reported a considerable negative impact from the pandemic on different aspects of their daily life, particularly emotional and psychological health and sleep patterns, which were more marked in younger patients and the older sub-group with frailty. Older patients without frailty reported the least impact on their functional status. DISCUSSION: There is a need for more personalised outpatient consultation options during cancer care. Whilst there is a preference for face-to-face consultations for older patients, following the pandemic there is a growing acceptance of remote consultations particularly during anti-cancer treatment. Older patients with lung cancer without frailty were less affected by the pandemic than those with frailty and younger patients, requiring less support from healthcare services.

Isolated recurrence of ovarian serous adenocarcinoma to adrenal gland.

Objectives: The purpose of this report was to present the diagnosis and management of an unusual case of a woman with ovarian carcinoma who developed an isolated recurrence to the adrenal gland six years after initial diagnosis. Case: A 79-year-old woman was diagnosed with stage IVa high-grade serous carcinoma of the ovary with malignant pleural effusion in January 2014. She received six cycles of carboplatin and paclitaxel and underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and optimal tumor debulking in May 2014. After developing new liver implants in August 2015 and peritoneal carcinomatosis in April 2016, she received 5 cycles of carboplatin and paclitaxel and 6 cycles of doxorubicin, respectively, after which she had no evidence of disease. In March 2020, a surveillance computed tomography (CT) scan showed a 1-cm interval thickening of the left adrenal gland suspicious for metastasis. Positron emission tomography (PET) scan revealed an adrenal mass that was intensely fluorodeoxyglucose (FDG) avid with subsequent fine-needle aspiration (FNA) consistent with metastatic serous carcinoma. She was treated with laparoscopic left adrenalectomy in October 2020 and underwent 4 cycles of adjuvant carboplatin and paclitaxel. Follow-up CT imaging revealed stable post-adrenalectomy status with no interval thickening of the gland and post-operative Ca-125 level of 11.2 from 26.1 pre-operatively. Conclusions: Interval adrenal thickening detected on surveillance CT was the most important initial indicator of adrenal metastasis in this case of ovarian carcinoma. The adrenal mass was further evaluated using PET CT and FNA for pathology diagnosis. As this new recurrence occurred in a patient with no evidence of disease, we suggested an aggressive management approach consisting of surgical excision in combination with chemotherapy to eliminate visible disease and optimize survival.

Developing an Agnostic Risk Prediction Model for Early AKI Detection in Cancer Patients.

Acute kidney injury (AKI) is a common complication among oncology patients associated with lower remission rates and higher mortality. To reduce the impact of this condition, we aimed to predict AKI earlier than existing tools, to allow clinical intervention before occurrence. We trained a random forest model on 597,403 routinely collected blood test results from 48,865 patients undergoing cancer treatment at The Christie NHS Foundation Trust between January 2017 and May 2020, to identify AKI events upcoming in the next 30 days. AKI risk levels were assigned to upcoming AKI events and tested through a prospective analysis between June and August 2020. The trained model gave an AUROC of 0.881 (95% CI 0.878-0.883), when assessing predictions per blood test for AKI occurrences within 30 days. Assigning risk levels and testing the model through prospective validation from the 1st June to the 31st August identified 73.8% of patients with an AKI event before at least one AKI occurrence, 61.2% of AKI occurrences. Our results suggest that around 60% of AKI occurrences experienced by patients undergoing cancer treatment could be identified using routinely collected blood results, allowing clinical remedial action to be taken and disruption to treatment by AKI to be minimised.

Incidence, Etiology, and Risk Factors of Clinical Mastitis in Dairy Cows under Semi-Tropical Circumstances in Chattogram, Bangladesh.

Clinical mastitis (CM) is an important production disease in dairy cows, but much of the knowledge required to effectively control CM is lacking, specifically in low-income countries where most farms are small and have specific dairy management, such as regular udder cleaning and practicing hand milking. Therefore, we conducted a 6-month-long cohort study to (a) estimate the incidence rate of clinical mastitis (IRCM) at the cow and quarter level, (b) identify risk factors for the occurrence of CM, (c) describe the etiology of CM, and (d) quantify antimicrobial susceptibility (AMS) against commonly used antimicrobial agents in S. aureus and non-aureus Staphylococcus spp. (NAS) in dairy farms in the Chattogram region of Bangladesh. On 24 farms, all cows were monitored for CM during a 6-month period. Cases of CM were identified by trained farmers and milk samples were collected aseptically before administering any antimicrobial therapy. In total, 1383 lactating cows were enrolled, which totaled 446 cow-years at risk. During the study period, 196 new cases of CM occurred, resulting in an estimated crude IRCM of 43.9 cases per 100 cow-years, though this varied substantially between farms. Among the tested CM quarter samples, Streptococci (22.9%) followed by non-aureus staphylococci (20.3%) were the most frequently isolated pathogens and resistance of S. aureus and NAS against penicillin (2 out of 3 and 27 out of 39 isolates, respectively) and oxacillin (2 out of 3 and 38 out of 39 isolates, respectively) was common. The IRCM was associated with a high milk yield, 28 to 90 days in milk, and a higher body condition score. Our results show that there is substantial room for udder health improvement on most farms.

Unknotting the interactive effects of learning processes on cultural evolutionary dynamics.

Forms of non-random copying error provide sources of inherited variation yet their effects on cultural evolutionary dynamics are poorly understood. Focusing on variation in granny and reef knot forms, we present a mathematical model that specifies how these variant frequencies are affected by non-linear interactions between copying fidelity, mirroring, handedness and repetition biases. Experiments on adult humans allowed these effects to be estimated using approximate Bayesian computation and the model is iterated to explain the prevalence of granny over reef knots in the wild. Our study system also serves to show conditions under which copying fidelity drives heterogeneity in cultural variants at equilibrium, and that interaction between unbiased forms of copying error can skew cultural variation.

Perceptions of physical activity engagement among adults with rheumatoid arthritis and rheumatologists.

AIM: Physical activity (PA) among adults with rheumatoid arthritis (RA) is suboptimal. This study assessed PA motivations and perceptions in adults with RA and rheumatologists. METHODS: Patients and rheumatologists participated in structured interviews led by a behavioral scientist. Sessions were audiotaped, transcribed and coded. RESULTS: Twenty-three patients (mean age = 63 [standard deviation = 10], 96% female) and seven rheumatologists (57% male, 29% fellows) participated. Nine themes emerged: communication with the rheumatologist, environment/access, symptom management, social support, mental health, breaking inactivity cycles, integrating PA into routines, staying in control and challenge/intimidation. Highly active patients viewed PA differently than low active patients. The need to compete with RA-free individuals may impede PA. CONCLUSION: Understanding how patients conceptualize PA will enable clinicians to formulate PA strategies to motivate patients.