Immunotherapy utilization patterns in patients with advanced cancer and autoimmune disease.

PURPOSE: Immunotherapy has been shown to improve cancer survival, but there are no consensus guidelines to inform use in patients with both cancer and autoimmune disease (AD). We sought to examine immunotherapy utilization patterns between cancer patients with and without AD. PATIENTS AND METHODS: This retrospective cohort study utilized data from a de-identified nationwide oncology database. Patients diagnosed with advanced melanoma, non-small cell lung cancer, and renal cell carcinoma were included. Outcomes of interest included first-line immunotherapy, overall immunotherapy, and number of immunotherapy cycles. We used logistic and Poisson regression models to examine associations between AD and immunotherapy utilization patterns. RESULTS: A total of 25,076 patients were included (796 with AD). Patients with AD were more likely to be female, White, receive care at academic centers, and have ECOG ≥ 3. Controlling for demographic and clinical variables, AD was associated with lower odds of receiving first-line (odds ratio [OR] = 0.68, 95% confidence interval [CI] 0.56-0.82) and overall (OR = 0.80, 95% CI 0.67-0.94) immunotherapy. Among patients who received at least one cycle of immunotherapy, there was no difference in mean number of cycles received between patients with and without AD (11.3 and 10.5 cycles respectively). The incident rate of immunotherapy cycles received for patients with AD was 1.03 times that of patients without AD (95% CI 1.01-1.06). DISCUSSION: Patients with AD were less likely to receive immunotherapy as first-line and overall therapy for treatment of their advanced cancer. However, among those who did receive at least one cycle of immunotherapy, patients with AD received a similar number of cycles compared to patients without AD. This not only indicates that AD is not an absolute contraindication for immunotherapy in clinical practice but may also demonstrate overall treatment tolerability and net benefit in patients with AD.

The Impact of the Pandemic on the Quality of Colorectal and Anal Cancer Care, and 2-Year Clinical Outcomes.

We undertook a retrospective study to compare the quality of care delivered to a cohort of newly diagnosed adults with colon, rectal or anal cancer during the early phase of COVID-19 (02/20-12/20) relative to the same period in the year prior (the comparator cohort), and examine the impact of the pandemic on 2-year disease progression and all-cause mortality. We observed poorer performance on a number of quality measures, such as approximately three times as many patients in the COVID-19 cohort experienced 30-day post-surgical readmission (10.5% vs. 3.6%; SD:0.27). Despite these differences, we observed no statistically significant adjusted associations between COVID-19 and time to either all-cause mortality (HR: 0.88, 95% CI: 0.61-1.27, p = 0.50) or disease progression (HR: 1.16, 95% CI: 0.82-1.64, p = 0.41). However, there was a substantial reduction in new patient consults during the early phase of COVID-19 (12.2% decrease), which appeared to disproportionally impact patients who traditionally experience sociodemographic disparities in access to care, given that the COVID-19 cohort skewed younger and there were fewer patients from neighborhoods with the highest Housing and Dwelling, ands Age and Labour Force marginalization quintiles. Future work is needed to understand the more downstream effects of COVID-19 related changes on cancer care to inform planning for future disruptions in care.

Interventions for Concerning Patient-Reported Outcomes in Routine Cancer Care: A Systematic Review.

IMPORTANCE: Collecting patient-reported outcomes (PROs) in routine cancer care improves patient-clinician communication, decision making, and overall patient satisfaction. Recommendations exist regarding standardized ways to collect, store, and interpret PRO data. However, evidence on incorporating PROs into cancer process of care, especially the type of HIs that are warranted after observing a concerning PRO and the effectiveness of these HIs are lacking. OBJECTIVE: This study summarizes HIs triggered after PRO completion and their effectiveness in improving patient outcomes for adults being treated for cancer types that are resource intensive and associated with high symptom burden [i.e., gastrointestinal (GI), lung, and head and neck cancer (HNC)]. Secondary outcomes included factors associated with poor implementation of PROs. EVIDENCE REVIEW: A literature search of peer-reviewed publications on MEDLINE, CINAHL Plus, APA PsycInfo, Scopus, and Cochrane was conducted following PRISMA guidelines from 1 January 2012, to 31 July 2022. Trial and real-world studies describing HIs after PRO completion for adult patients being treated for GI, lung, and HNC were included. Sixteen studies involving 144,496 patients were included. The Joanna Briggs Institute critical appraisal checklist was used to assess risk of bias. FINDINGS: Of the 16 included studies, 5 included patients with HNC. Commonly used PRO measurement tools were the PRO-CTCAE and ESAS. Only three studies reported specific HIs delivered in response to concerning PROs and measured their effectiveness on patient outcomes. In all three studies, these HIs significantly improved cancer-related care. The most common HIs undertaken in response to concerning PROs were referrals to other specialists/allied healthcare professionals, medication changes, or self-management advice. Provider-related barriers to PRO measurement and delivery included the overwhelming number of alerts, the time required to address each PRO and the unclear role of healthcare providers in response to these alerts. Patient-related barriers included lower digital literacy and socioeconomic status, older age, rural living, and patients suffering from GI and HNC. CONCLUSIONS AND RELEVANCE: This review highlights that PRO-triggered HIs are heterogenous and can improve patient quality of life. Further studies are necessary to determine the types of interventions with the greatest impact on patient care and outcomes.

Legislative and judicial responses to public health protection under eco-environmental damage relief in China.

Background: The group-type health damage caused by eco-environmental damage has been stated in the Environmental Protection Law and other laws in China. The first-ever Chinese Civil Code, which took effect in 2021, has explicitly defined eco-environmental damage relief and imposed affirmative duties on those who polluted the environment or destroyed the ecology. This study aims to describe the status quo of public health protection in eco-environmental damage relief and explore its progress and limits in protecting public health. Methods: By reviewing China's legislation on relief of eco-environmental damage and observing the implementation of these laws in judicial practice. All judicial cases of eco-environmental damage published by Chinese courts from January 2021 to May 2023 were selected and examined. From the perspective of the comparison of laws, the measurement of interests and the execution of cases, we discussed the issues of China's legislative and judicial responses to public health. Results: The relief system of eco-environmental damage in China has been formed initially, but there are still some deficiencies: In the application of law for relief of public health, there are many choices of means, resulting in the choice conflict of law application; the public health damage in the eco-environmental damage case has been ignored by courts, and it has not been a dominant consideration element; the objects of the execution of the cases are directed to the pure eco-environmental restoration, and the restoration plan does not cover public health protection measures, which does not have a preventive effect on public health. The root cause of problems is that the relief of eco-environmental damage in China follows the logic of traditional private law. Conclusion: The issues mentioned above merit consideration in China's future law revisions and judicial practice. Based on the dual nature of public and private law in environmental health, it is necessary to adjust the provisions of responsibility for eco-environmental restoration from the framework of public law, including the scope and mechanism, and then further suggestion includes the legal subject, the benefit element and the use of funds.

Comprehensive genome sequence analysis of the devastating tobacco bacterial phytopathogen Ralstonia solanacearum strain FJ1003.

Due to its high genetic diversity and broad host range, Ralstonia solanacearum, the causative phytopathogen of the bacterial wilt (BW) disease, is considered a "species complex". The R. solanacearum strain FJ1003 belonged to phylotype I, and was isolated from the Fuzhou City in Fujian Province of China. The pathogen show host specificity and infects tobacco, especially in the tropical and subtropical regions. To elucidate the pathogenic mechanisms of FJ1003 infecting tobacco, a complete genome sequencing of FJ1003 using single-molecule real-time (SMRT) sequencing technology was performed. The full genome size of FJ1003 was 5.90 Mb (GC%, 67%), containing the chromosome (3.7 Mb), megaplasmid (2.0 Mb), and small plasmid (0.2 Mb). A total of 5133 coding genes (3446 and 1687 genes for chromosome and megaplasmid, respectively) were predicted. A comparative genomic analysis with other strains having the same and different hosts showed that the FJ1003 strain had 90 specific genes, possibly related to the host range of R. solanacearum. Horizontal gene transfer (HGT) was widespread in the genome. A type Ⅲ effector protein (Rs_T3E_Hyp14) was present on both the prophage and genetic island (GI), suggesting that this gene might have been acquired from other bacteria via HGT. The Rs_T3E_Hyp14 was proved to be a virulence factor in the pathogenic process of R. solanacearum through gene knockout strategy, which affects the pathogenicity and colonization ability of R. solanacearum in the host. Therefore, this study will improve our understanding of the virulence of R. solanacearum and provide a theoretical basis for tobacco disease resistance breeding.

Identification of Key Gene Networks and Deciphering Transcriptional Regulators Associated With Peanut Embryo Abortion Mediated by Calcium Deficiency.

Peanut embryo development is easily affected by a variety of nutrient elements in the soil, especially the calcium level. Peanut produces abortive embryos in calcium-deficient soil, but underlying mechanism remains unclear. Thus, identifying key transcriptional regulators and their associated regulatory networks promises to contribute to a better understanding of this process. In this study, cellular biology and gene expression analyses were performed to investigate peanut embryo development with the aim to discern the global architecture of gene regulatory networks underlying peanut embryo abortion under calcium deficiency conditions. The endomembrane systems tended to disintegrate, impairing cell growth and starch, protein and lipid body accumulation, resulting in aborted seeds. RNA-seq analysis showed that the gene expression profile in peanut embryos was significantly changed under calcium deficiency. Further analysis indicated that multiple signal pathways were involved in the peanut embryo abortion. Differential expressed genes (DEGs) related to cytoplasmic free Ca2+ were significantly altered. DEGs in plant hormone signaling pathways tended to be associated with increased IAA and ethylene but with decreased ABA, gibberellin, cytokinin, and brassinosteroid levels. Certain vital genes, including apoptosis-inducing factor, WRKYs and ethylene-responsive transcription factors, were up-regulated, while key regulators of embryo development, such as TCP4, WRI1, FUS3, ABI3, and GLK1 were down-regulated. Weighted gene co-expression network analysis (WGCNA) identified 16 significant modules associated with the plant hormone signaling, MAPK signaling, ubiquitin mediated proteolysis, reserve substance biosynthesis and metabolism pathways to decipher regulatory network. The most significant module was darkolivegreen2 and FUS3 (AH06G23930) had the highest connectivity among this module. Importantly, key transcription factors involved in embryogenesis or ovule development including TCP4, GLK1, ABI3, bHLH115, MYC2, etc., were also present in this module and down regulated under calcium deficiency. This study presents the first global view of the gene regulatory network involved in peanut embryo abortion under calcium deficiency conditions and lays foundation for improving peanut tolerances to calcium deficiency by a targeted manipulation of molecular breeding.

Effects of High Anxiety Scores on Surgical and Overall Treatment Plan in Patients with Breast Cancer Treated with Neoadjuvant Therapy.

BACKGROUND: Patients with newly diagnosed breast cancer and high levels of anxiety often pursue more aggressive surgical interventions. The neoadjuvant treatment (NAT) setting could provide a window of opportunity to address patients' anxiety. However, the impact of anxiety on surgical decisions in the setting of NAT for breast cancer has not been previously studied. MATERIALS AND METHODS: A prospective database of patients with breast cancer treated with NAT at BC Cancer was used to identify patients treated with NAT and subsequent surgical resection. Patients with bilateral breast cancer or BRCA mutations or those referred to the hereditary cancer program were excluded. An anxiety score of 0-3 was assigned based on responses to the Edmonton Symptom Assessment System and Psychosocial Screen for Cancer. Clinicopathological information and treatment data were retrieved and cross-referenced between the low-anxiety (scores 0-1) and high-anxiety (scores 2-3) cohorts. RESULTS: From 2012 to 2016, 203 patients met eligibility criteria. Of these, 93 patients (45.8%) had low anxiety and 110 patients (54.2%) had high anxiety. Overall, 161 patients (79.3%) had locally advanced cancers; no differences in stage, grade, or biomarkers were found between the low- and high-anxiety cohorts. Patients with high self-reported anxiety at initial consultation were younger (mean 56 years vs. 60 years; p = .011) and more likely to undergo mastectomy for breast-conserving surgery-eligible disease and bilateral mastectomy for unilateral disease compared with those with low anxiety (37.3% vs. 18.3%; likelihood ratio 9.15; p = .002). No significant differences in treatment timelines were identified between the two cohorts. CONCLUSION: Patients with high anxiety at initial consultation were nine times more likely to undergo aggressive surgery compared with patients with low anxiety. These findings underscore the need for early identification of patients who may benefit from tailored supportive and educational services to address sources of anxiety and knowledge gaps. IMPLICATIONS FOR PRACTICE: The prevalence of anxiety among women with newly diagnosed breast cancer is being increasingly acknowledged. However, health care providers have not fully appreciated the impact of anxiety on the surgical management of patients with early-stage breast cancer. This study highlights the importance of self-reported anxiety on surgical management. The preoperative period provides a unique window of opportunity to address sources of anxiety and provide targeted educational materials over a period of 4-6 months, which may ultimately lead to less aggressive surgery when it is not needed.

Efficacy of Neoadjuvant Endocrine Therapy Versus Neoadjuvant Chemotherapy in ER-positive Breast Cancer: Results From a Prospective Institutional Database.

BACKGROUND: Although neoadjuvant chemotherapy (NACT) has been established as a standard for medically fit patients with locally advanced breast cancer, there has been renewed interest in utilizing neoadjuvant endocrine therapy (NET) for women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Rates of pathologic complete response (pCR) are known to be low, but data regarding down-staging and long-term outcomes are inconsistent. PATIENTS AND METHODS: A prospective institutional database of patients with breast cancer treated with neoadjuvant therapy from 2012 to 2017 was analyzed to identify patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Patients who received NET were compared with those who received NACT. A matched analysis (age, stage, grade) was performed to compare rates of down-staging, pCR, breast conserving surgery, and CPS+EG scores. RESULTS: A total of 176 patients met eligibility criteria. Of these, 111 (63%) patients received NACT, 51 (29%) received NET, and 14 (8%) received both sequentially. Women prescribed NET were older (65.5 vs. 51.2 years; P < .0001) and presented with lower clinical stage (P < .0001). The median duration of NET was 90 days. When matched, clinical down-staging was more frequent with NACT (20/51; 39%) compared with NET (11/51; 22%) (P = .032). Of these, 2% achieved pCR in each cohort. Conversion rates to breast conserving surgery eligibility were low (8% and 13% with NET and NACT; P = .70). No significant differences in CPS+EG scores were identified. CONCLUSIONS: Significantly higher rates of down-staging were achieved with NACT compared with NET when patients were matched. This study highlights the importance of establishing tumor biology and the need for biomarkers that can be used as predictive tools to inform treatment.

Effects of left dlPFC modulation on social cognitive processes following food sampling.

BACKGROUND: The dorsolateral prefrontal cortex (dlPFC) plays a central role in the inhibition of eating, but also the modulation of conscious thought processes that might precede, accompany or follow initial food tasting. The latter might be particularly important to the extent that post-tasting cognitions may drive prolonged eating beyond the satiety point. However, we know very little about the effect of the dlPFC on conation following initial food sampling. This investigation compared the effects of dlPFC attenuation using repetitive transcranial magnetic stimulation (rTMS) on social cognition following (Study 1) and prior to (Study 2) a food consumption opportunity. METHODS: In Study 1, participants (N = 21; Mage = 21 years) were randomized to active or sham continuous theta-burst stimulation (cTBS; an inhibitory variant of rTMS) targeting the left dlPFC followed by an interference task. Participants subsequently completed measures of attitudes, norms and perceived control following a mock taste test. In Study 2, a second sample of right handed participants (N = 37; Mage = 21 years) were assigned to active or sham cTBS, followed by an interference task and two measures of attitudes (implicit and explicit), both assessed prior to the same taste test paradigm. RESULTS: In Study 1, findings revealed a reliable effect of cTBS on post-tasting attitudes (t(1,19) = 3.055, p = .007; d = 1.34), such that attitudes towards calorie dense snack foods were significantly more positive following active stimulation than following sham stimulation. Similar effects were found for social norms (t(1,19) = 3.024, p = .007, d = 1.31) and perceived control (t(1,20) = 19.247, p < .001, d = 0.50). In Study 2, no effects of cTBS were observed on pre-consumption attitudes, despite reliable effects on interference scores and subsequent consumption. CONCLUSIONS: The left dlPFC may selectively modulate facilitative social cognition following initial food sampling (but not pre-consumption).

The effects of short-term continuous subcutaneous insulin infusion treatment on fasting glucagon-like peptide-1 concentrations in newly diagnosed type 2 diabetes.

OBJECTIVE: Early short-term intensive insulin therapy in newly diagnosed type 2 diabetes patients shows benefit in glycemic control and ß-cell function. Glucagon-like peptide-1 (GLP-1) plays an important role in glucose metabolism and development of type 2 diabetes. We did a study to observe the changes of GLP-1 and ß-cell function after short-term continuous subcutaneous insulin infusion (CSII) treatment. METHODS: A total of 66 subjects were enrolled, including 30 normal glucose tolerance controls (NGT) and 36 patients with newly diagnosed type 2 diabetes between October 2015 and July 2016. Fasting plasma glucose (FPG), insulin, and GLP-1 were measured in each subject. The patients underwent CSII treatment for 2 weeks, and then FBG, insulin, and GLP-1 were measured. HOMA-IR and HOMA-B were then calculated. RESULTS: All patients achieved target glycemic control in two weeks. HOMA-IR and HOMA-B improved significantly after intensive interventions (p < 0.05). The GLP-1 concentration increased significantly in patients after treatment (p < 0.05). When grouped according to bodyweight and age in all patients, the HOMA-IR changed significantly in overweight and old age subgroups, the HOMA-B increased significantly in normal weight, overweight and middle age subgroups, and the GLP-1 concentration also increased significantly in overweight and middle age subgroups respectively (p < 0.05). CONCLUSION: Short-term CSII treatment can obtain glycemic control target and recover ß-cell function and GLP-1 secretion in newly diagnosed type 2 diabetes patients. The overweight and middle-aged patients may get more benefit from this treatment.

[Variance of mean platelet volume in subjects with normal glucose tolerance, impaired glucose regulation and type 2 diabetic mellitus and its relationship with diabetic peripheral artery disease].

OBJECTIVE: To explore the variance of mean platelet volume (MPV) in subjects with normal glucose tolerance (NGT), impaired glucose regulation (IGR) and type 2 diabetes mellitus (T2DM) and risk factors of MPV changes and analyze the relationship between MPV and diabetic peripheral artery disease (PAD). METHODS: A total of 173 subjects were enrolled into this observational cross-sectional study. They were divided into 3 groups: NGT (n = 41), IGR (n = 41) and T2DM (n = 91). Blood pressure (BP), platelet count (PLT), mean platelet volume (MPV) and such fasting serum lipids as triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), fast plasma glucose (FPG) and serum uric acid (UA) were determined. HbA1c and ankle/brachial index (ABI) were also measured. RESULTS: (1) The MPV level was highest in the T2DM group (12.3 ± 1.5) fl. And it was significantly higher in the IGR group than in the NGT group (9.7 ± 0.9 vs 8.0 ± 0.9) fl (P < 0.01). It was significantly higher in diabetics with HbA1c ≥ 7% (13.2 ± 1.9) fl than in patients those with HbA1c 7% (11.8 ± 1.7) fl (P < 0.01); (2) Stepwise multiple regression analysis showed that age, serum creatinine, LDL-C and fasting plasma glucose (FPG) were important influencing factors of MPV (adjusted R(2) = 0.891); (3) Multiple Logistic regression analysis indicated that MPV was an important risk factor of PAD. CONCLUSION: The MPV level in T2DM is significantly higher than that in NGT and IGR subjects. FPG, LDL-C, age and serum creatinine are important contributors to MPV. And MPV is an important risk factor of PAD.

[Effects of L-threonate on bone resorption by osteoclasts in vitro].

OBJECTIVE: To clarify if calcium L-threonate and sodium L-threonate have inhibitory effects on the bone resorption of rabbit's osteoclasts in vitro. METHODS: This study contained a total of 16 culture groups, including one group as control and 5 groups treated by 5 drugs (calcium D-threonate, sodium L-threonate, alendronate, 17beta-estradiol and calcium gluconate) each at the final concentrations of 10(-9) mol/L, 10(-7) mol/L, 10(-5) mol/L respectively. After 7 days, eight bone slices of every group were stained with toluidine blue and the areas of resorptive pits were analyzed under light microscope; the concentrations of C-telopeptide of type I collagen (CTx or Crosslaps) in culture supernatants were measured by ELISA. RESULTS: (1) The resorption area and the CTx concentration of the Calcium L-threonate groups were reduced significantly as compared with those of control and of Calcium gluconate groups respectively. The resorption area and CTx level of the Sodium L-threonate groups were significantly reduced when compared with those of the control, but the effects of Calcium gluconate groups were not so. (2) The reduction in the resorption area and CTx concentration of Calcium L-threonate group was more than that of Sodium L-threonate group. (3) The reductive effect of the high concentration (10(-5)) group of Calcium L-threonate on the area and CTx level was corresponding to that of 17beta-estradiol at a concentration between 10(-7) and 10(-9). (4) The resorption area was related to the CTx concentration (r=0.876). (5) The CTX level was much more sensitive, precise and stable than the concentration. CONCLUSION: L-threonate, especially calcium L-threonate could inhibit the bone resorption of osteoclasts in vitro, and its effect might be related to the radical of L-threonic acid. The CTx concentration in culture supernatants might be an effective marker quantitatively reflecting the bone resorption by osteoclasts in vitro.