Long-term combined blockade of CXCR4 and PD-L1 with in vivo reassembly for intensive tumor interference.

Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly (p < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings.

Intervention to reduce loneliness among older adults in the community: Making friends with volunteers.

AIM: This study aimed to examine the effects of providing a program that introduced volunteers to make friends with older adults to reduce loneliness and increase loneliness literacy. METHODS: Eight community development associations in Taiwan participated in the study. In the first stage, older people living alone or with only a spouse, or those with a family, but without substantial interactions, were screened for loneliness. Older adults with a higher risk of loneliness were given priority to be invited to participate in this intervention. This 3-month intervention program was designed by each community development association and delivered at the older adults' homes. A total of 87 older persons completed both waves of the interviews. RESULTS: Loneliness was reduced (UCLA-6 Loneliness Scale scores decreased from 13.5 to 11.6), and loneliness literacy improved (loneliness literacy scores increased from 38.9 to 42.0) compared with what it was before the program. In a generalized linear model, when controlling for covariates, loneliness was reduced, but not significantly (B = -0.934, P > 0.05), whereas loneliness literacy improved significantly for older participants (B = 2.088, P < 0.05). CONCLUSIONS: Making friends with older adults who are lonely might improve their loneliness literacy. Geriatr Gerontol Int 2024; 24: 240-245.

Hereditary transthyretin cardiac amyloidosis proven by endomyocardial biopsy: a single-centre retrospective study and literature review.

BACKGROUND: This study aimed to report the genotypes and phenotypes of hereditary transthyretin cardiac amyloidosis (hATTR-CA) in a Western Chinese cohort and review the genetic profiles of this disorder in the Chinese population. METHODS: Transthyretin (TTR) gene sequencing of probands diagnosed with TTR cardiac amyloidosis and their relatives was performed at West China Hospital of Sichuan University from January 2018 to December 2021. All patients underwent endomyocardial biopsy for light and electron microscopy examinations. Clinical and essential examination materials were retrospectively collected and analysed. RESULTS: TTR gene alteration was demonstrated in five probands and their two relatives. Three TTR variants were identified, namely, Ser23Asn, Glu54Leu and Thr60Ala. This study is the first to report Glu54Leu as pathogenic mutations in Chinese hATTR-CA patients. The Ser23Asn mutation was the most common mutation in this cohort. Five probands, including two males and three females, were all ethnic Han-Chinese. The median age at diagnosis and delay in diagnosis (interval from onset to diagnosis) was 56 years (range, 54-69 years) and 8 years (range, from 1 to 30 years), respectively. Three cases showed a defined family history of amyloidosis. Endomyocardial biopsies and TTR immunohistochemistry showed positive results in all patients. Two probands died 17.0 months and 21.0 months after diagnosis. CONCLUSIONS: We identified one novel TTR variants causing hATTR-CA in the West Han Chinese population. To avoid misdiagnosis or delayed diagnosis of hATTR-CA, TTR genotypic screening and endomyocardial biopsy should be performed as soon as possible in cases with heightened clinical suspicion.

Rare Extranodal Manifestation of Rosai-Dorfman Disease Presenting as Nasal Obstruction and its Management.

Rosai-Dorfman disease (RDD) is a rare and benign lymphoproliferative disorder that commonly presents as painless, bilateral neck swelling. Extranodal presentations are considered rare, but the most common extranodal locations involved include skin, subcutaneous followed by nasal/paranasal sinuses. Although it is a benign condition, it may be mistaken as a malignant lesion and requires a biopsy for diagnostic confirmation. In this study, we report a rare case of RDD with bilateral neck node and nasal/paranasal sinus involvement which initially presented with bilateral nasal obstruction. And, we reviewed the management in this unusual case and discussed the helpful role imaging studies play in the further workup and subsequent follow-up to treatment response.

Assessing Geographic Variation in Rates of Cervical Cancer and Recurrent or Metastatic Cervical Cancer Among Medicaid Enrollees.

OBJECTIVE: The objective of this study was to evaluate trends in prevalence of cervical cancer (CC) and rates of recurrent or metastatic cervical cancer (r/mCC) treatment initiation at the state and metropolitan statistical area (MSA) levels among Medicaid enrolled females from 2016 to 2019. METHODS: Retrospective analyses of nationwide Medicaid claims data were used to identify adult CC and r/mCC patients from 2016 to 2019. CC prevalence was estimated as the proportion of females diagnosed with CC out of all adult female Medicaid beneficiaries, and r/mCC by the proportion of CC patients who initiated a systemic treatment not associated with surgery or radiation to the number of enrollees with CC diagnosis in each state or MSA. Overall and annual rates were calculated for each state and MSA from 2016 to 2019. RESULTS: The analytic cohort included 70,865 adult female Medicaid beneficiaries with CC from 2016 to 2019, among whom 3375 were identified as r/mCC patients. Nationwide annual prevalence of CC remained relatively stable from 2016 to 2019, while r/mCC decreased slightly over the study period. Several MSAs experienced increasing rates of r/mCC from 2016 to 2019, including Mayaguez, PR, Aguadeilla-Isabela, PR, and Green Bay, WI. CONCLUSIONS: Claims data demonstrate areas in the United States with disproportionately high or increasing CC or r/mCC burden, indicating a potential gap in preventative care for females and an unmet need for education and health care resource allocation. Future research should evaluate associations between community-level factors and r/mCC burden.

Patterns of care and health care resource use among Medicaid-enrolled women with recurrent or metastatic cervical cancer.

BACKGROUND: Cervical cancer is a public health challenge and remains a disease with high unmet need. Previous real-world studies demonstrated significant variability in treatments for patients with recurrent or metastatic cervical cancer (r/mCC). A large proportion of patients with cervical cancer are insured through Medicaid; however, previous studies examining treatment patterns for r/mCC have not included Medicaid patients. As the r/mCC treatment landscape continues to evolve, there is a need to understand current real-world unmet need among patients with r/mCC enrolled in Medicaid. OBJECTIVE: To evaluate treatment patterns and health care resource utilization (HCRU) among Medicaid-enrolled women with r/mCC. METHODS: This is a retrospective analysis of nationwide Medicaid claims to assess patient characteristics, treatment patterns, and HCRU among patients with r/mCC between 2016 and 2019. First-line treatment (1L) for r/mCC was defined by the first administration of systemic therapy without concomitant radiation or surgery. Patient characteristics, treatment patterns, and HCRU were characterized by line of therapy. RESULTS: A total of 3,375 eligible adult female patients initiated systemic treatment for r/mCC between 2016 and 2019. Mean age at treatment initiation was 52.9 (SD ± 12.8) years. Nearly 1,300 (1,294, 38.3%) women had evidence of receiving second-line treatment (2L), with nearly one-third (N = 420) of those also having evidence of third-line treatment. The majority (60.5%) of 1L regimens were doublet chemotherapy ± bevacizumab, consistent with treatment guidelines. In contrast, no clear preferred treatment choice was observed among patients receiving 2L or later (2L+) therapy. Notably, immunotherapy accounted for 21.6% of treatment regimens in 2L/3L overall, with its use increasing substantially over time (<6% in 2016 to 40.8% in 2019). Despite increased use of immunotherapy, however, most patients did not remain on treatment for prolonged durations (immunotherapy median duration 2.2 months vs 2.4 months for nonimmunotherapy; P = 0.5). Across most HCRU measures (inpatient admissions, outpatient visits, emergency department visits, and pharmacy claims), 2L+ patients had significantly less utilization per patient compared with 1L patients in unadjusted analyses. CONCLUSIONS: This analysis found that the majority of Medicaid patients with r/mCC received guideline-recommended standard of care in 1L between 2016 and 2019. However, there was no clear standard of care for patients with 2L+ r/mCC enrolled in Medicaid over this time period. Although immunotherapy use is increasing, short durations of treatment suggest a potential unmet medical need among this population. New therapies should provide meaningful clinical benefit without significant increase in HCRU for Medicaid enrollees needing treatment for r/mCC. DISCLOSURES: Dr Leath has received consulting fees from Seagen Inc. for service on Scientific Advisory Boards, cervical cancer research funding from Agenus, Rubius Therapeutics, and Seagen Inc., and funding from the NCI UG1 CA23330 and P50 CA098252. Dr Ting and Dr Zhang are employees and stock owners of Seagen Inc. Mr Fiori and Dr Pauly are current employees and Ms Nysenbaum is a former employee of Manatt Health Strategies, which received funding from Seagen Inc. to conduct the study described here. Manatt Health Strategies has also previously received consulting fees from other pharmaceutical companies that they are not permitted to publicly disclose. This research was funded by Seagen Inc. Seagen Inc. conceptualized the study approach, methodology, and contributed to article writing and review but was not involved in data acquisition, manipulation, or analysis.

Cervical cancer geographical burden analyzer: An interactive, open-access tool for understanding geographical disease burden in patients with recurrent or metastatic cervical cancer.

OBJECTIVE: Cervical cancer (CC) disproportionately affects women based on socioeconomic status and racial/ethnic background. There is limited research in quantifying and visualizing whether substantial geographical disparities in the US exist with respect to CC burden, and especially with respect to recurrent or metastatic CC (r/mCC) disease burden. Identifying regions with higher r/mCC burden may help inform effective healthcare resource allocation and navigating patients to appropriate care. METHODS: We conducted a retrospective analysis of the 2015-2020 MarketScan® Commercial and Supplemental Medicare claims data; r/mCC burden was estimated as the number of patients initiating r/mCC systemic therapy over CC-diagnosed patients for each of the 410 metropolitan statistical areas (MSAs) considered. We developed a public, web-based tool, the Cervical Cancer Geographical Disease Burden Analyzer (Cervical Cancer Geo-Analyzer, http://www.geo-analyzer.org), that allows users to visualize r/mCC burden across MSAs over multiple years. RESULTS: There was considerable variation in r/mCC burden across MSAs, with a range of 0-83.3%. Burden increased in Boston-Cambridge-Newton, MA (r/mCC to CC ratio: 41% in 2018 to 50% in 2020), and Sacramento-Roseville-Arden-Arcade, CA (33% in 2018 to 50% in 2020). On the other hand, while r/mCC burden remained high, it decreased in Grand Rapids, MI (55% in 2018 to 31% in 2020) and San Francisco-Oakland-Hayward, CA (40% in 2018 to 26% in 2020). There were regions with sparse or no data, suggesting a need for more representative data capture. CONCLUSION: The Cervical Geo-Analyzer is a tool to visualize areas with high need for CC interventions. It also builds the foundation for further work to understand local risk factors of disease burden, identify populations of interest, characterize health disparities of CC or r/mCC and inform targeted interventions.

Factors associated with receipt of second-line recurrent or metastatic cervical cancer treatment in the United States: A retrospective administrative claims analysis.

Purpose: Contemporary, real-world data on eligible patients receiving treatment following progression on first-line (1L) recurrent or metastatic cervical cancer (r/mCC) therapy are needed to inform treatment algorithms and identify potential gaps in the r/mCC care continuum. Methods: This study estimated the prevalence and predictors of second-line (2L) r/mCC therapy among 1L-treated patients using the 2015-2020 IBM MarketScan® commercial claims database. Women ≥ 18 years diagnosed with cervical cancer and treated with first-line systemic therapies were identified and followed for 12 months from their 1L therapy end date. Women with claims for a new therapy after 60 days but no later than 365 days from the end of 1L treatment were identified as those who progressed and received 2L therapy for r/mCC. Descriptive statistics examined baseline cohort characteristics and multivariable logistic regression model examined the factors associated with receiving 2L treatment. Results: We identified 384 1L-treated patients with r/mCC with ≥ 12 months of follow-up post-1L treatment. During follow-up, over half (51.0 %) of the 1L-treated r/mCC patients received 2L treatment. Patients from the South and Midwest had a lower likelihood of receiving 2L treatment compared with those living in the Northeast (adjusted odds ratio [aOR] = 0.43; 0.23-0.84) and (aOR = 0.52; 0.28-0.95, respectively). Patients not treated with bevacizumab in 1L were also less likely to receive 2L therapy (aOR = 0.65; 0.43-0.99). Conclusion: Additional research and targeted outreach efforts are needed to understand geography-, population-, or practice-specific barriers impacting access to 2L therapy among patients with r/mCC.

Predictors of Basic Activity in Daily Living and Length of Hospitalization in Patients with COVID-19.

BACKGROUND: Patients recovered from COVID-19 often suffer from the sequelae of the disease, which can hinder the patients' activity in daily living. Early recognition of the patients at risk of prolonged hospitalization and impaired physical functioning is crucial for early intervention. We aim to identify the predictors of prolonged hospitalization and impaired activity in daily living in this study. METHODS: COVID-19 patients hospitalized in a medical center were divided into two groups according to the Barthel index three months after discharge and the median length of hospital stay, respectively. Chi-square test and Mann-Whitney U test were performed to check the differences between the two groups in patient characteristics as well as hematology tests at the emergency department, the intensive care unit mobility scale (ICUMS), and the medical research council sum score (MRCSS). Logistic regression and the receiver operating characteristic curve analysis were further performed for the factors with significant differences between the two groups. RESULTS: Both ICUMS and MRCSS showed significant differences between the groups. The ICUMS had an odds ratio of 0.61 and the MRCSS of 0.93 in predicting a Barthel index score less than 100 three months after discharge. The MRCSS had an odds ratio of 0.82 in predicting a prolonged length of hospital stay. CONCLUSION: Both ICUMS and MRCSS upon admission are predictive of a Barthel index score of less than 100 three months after discharge. On the other hand, only MRCSS has predictive value of a prolonged hospitalization.

Real-world treatment drop-off among recurrent or metastatic cervical cancer patients: A US community oncology-based analysis.

OBJECTIVE: Understanding real-world treatment patterns and proportions of eligible patients in each line of treatment is imperative to inform future clinical trial designs and multi-line treatment algorithm development. METHODS: We conducted a retrospective observational cohort study of adult women who received first-line (1 L) therapy for r/mCC between 01 September 2014 and 31 December 2019, using The US Oncology Network electronic health records and chart review data. Patients were followed to 31 December 2020. Patient demographic and clinical characteristics, treatment patterns, and clinical outcomes were assessed descriptively. RESULTS: A total of 262 patients with r/mCC met study inclusion criteria (mean age = 53 years). The majority of patients in 1 L received platinum-based chemotherapy doublet plus bevacizumab (66%) or chemotherapy doublet alone (24%). Nearly half the patients (48%) completing 1 L received 2 L therapy. Among these patients, there was no consistent 2 L treatment of choice. Overall median time to treatment discontinuation was 3.5 months from 1 L treatment initiation, and median overall treatment-free interval was 2.1 months from 1 L discontinuation. Besides elevated serum creatinine, abnormal BMI indicated a directional trend for lower likelihood of receiving 2 L. Other predictors may include no prior bevacizumab, worse ECOG, and earlier disease prevention. CONCLUSIONS: >50% of the patients who initiated 1 L treatment did not receive 2 L therapy, highlighting the need for novel and effective treatment options. As the treatment landscape continues to evolve, we anticipate that more patients will live longer with more treatment options across multiple lines of therapies in the r/mCC setting.

BAHD1 serves as a critical regulator of breast cancer cell proliferation and invasion.

Breast cancer patients with lymphatic metastasis suffer from poor prognoses. There is an urgent need for controlling lymph node metastasis, but it has proven challenging so far. Here, we implemented LASSO analysis of The Cancer Genome Atlas database to identify genes related to lymph node metastasis and prognosis, and 15 genes were selected. We constructed a functional protein association network and univariate Cox regression to identify significant genes. The results showed that BAHD1 could be predictive of lymph node metastasis as well as prognosis. In vitro studies demonstrated that BAHD1 exerted appreciable effects on the proliferation, migration, and invasion capacity of breast cancer cells. Furthermore, downregulation of BAHD1 induced cell cycle arrest in G1 phase. Additionally, the mRNA levels of CCND1, CDK1 and YWHAZ were decreased upon BAHD1 silencing. These findings indicate that the expression of BAHD1 is essential in the progression of breast cancer, which may provide novel therapeutic and diagnostic clues and insights into the prevention of lymph node metastasis in breast cancer.

Trends in treatment patterns and costs of care among patients with advanced stage cervical cancer.

BACKGROUND: Current treatments for recurrent or metastatic cervical cancer (r/mCC) do not offer satisfactory clinical benefits, with most patients progressing beyond first-line (1L) treatment. With new treatments under investigation, understanding current treatment patterns, the impact of newly approved therapies, and total costs of care for r/mCC are important. METHODS: A retrospective analysis of a US commercial insurance claims database to identify adult patients with r/mCC between 2015 and Q1-2020; defining 1L treatment as the first administration of systemic treatment without concomitant chemoradiation or surgery. Patient characteristics, treatment regimens, duration of therapy, and total costs of care were evaluated for each line of therapy. RESULTS: 1323 women initiated 1L treatment for r/mCC (mean age, 56.1 years; mean follow-up, 16.5 months). One-third (n = 438) had evidence of second-line (2L) treatment; of these, 129 (29%) had evidence of third-line (3L) treatment. No regimen represented a majority among 2L+ treatments. The 2018 approval of pembrolizumab led to increased 2L immunotherapy use (0% in 2015, 37% in 2019/Q1-2020). However, only a small proportion of patients stayed on immunotherapy for a prolonged period. Mean per-patient-per-month total costs of care during treatment were $47,387 (1L), $77,661 (2L), and $53,609 (3L), driven primarily by outpatient costs. CONCLUSIONS: No clear standard of care was observed in 2L+. Although immunotherapy is increasingly used in 2L+, only a small subset of patients stayed on immunotherapy for a prolonged period, suggesting a need for more therapeutic options. Better understanding of disease biology and the introduction of new therapies may address these unmet needs.

Factors associated with receipt of second-line recurrent or metastatic cervical cancer treatment in the United States: A retrospective administrative claims analysis.

Purpose: Contemporary, real-world data on eligible patients receiving treatment following progression on first-line (1L) recurrent or metastatic cervical cancer (r/mCC) therapy are needed to inform treatment algorithms and identify potential gaps in the r/mCC care continuum. Methods: This study estimated the prevalence and predictors of second-line (2L) r/mCC therapy among 1L-treated patients using the 2015-2020 IBM MarketScan® commercial claims database. Women ≥ 18 years diagnosed with cervical cancer and treated with first-line systemic therapies were identified and followed for 12 months from their 1L therapy end date. Women with claims for a new therapy after 60 days but no later than 365 days from the end of 1L treatment were identified as those who progressed and received 2L therapy for r/mCC. Descriptive statistics examined baseline cohort characteristics and multivariable logistic regression model examined the factors associated with receiving 2L treatment. Results: We identified 384 1L-treated patients with r/mCC with ≥ 12 months of follow-up post-1L treatment. During follow-up, over half (51.0 %) of the 1L-treated r/mCC patients received 2L treatment. Patients from the South and Midwest had a lower likelihood of receiving 2L treatment compared with those living in the Northeast (adjusted odds ratio [aOR] = 0.43; 0.23-0.84) and (aOR = 0.52; 0.28-0.95, respectively). Patients not treated with bevacizumab in 1L were also less likely to receive 2L therapy (aOR = 0.65; 0.43-0.99). Conclusion: Additional research and targeted outreach efforts are needed to understand geography-, population-, or practice-specific barriers impacting access to 2L therapy among patients with r/mCC.

Use of acid-suppressive drugs and risk of fracture in children and young adults: a meta-analysis of observational studies.

BACKGROUND: Acid-suppressive drugs (ASDs) are being used by increasing number of children and young adults. However, evidence for a relationship between ASD use and the risk of fracture in these groups of patients is conflicting. We conducted a meta-analysis to evaluate the risk of fracture in children and young adults exposed to ASDs. METHODS: A literature search was performed using the PUBMED, EMBASE, and Cochrane Library databases from inception to November 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to determine the relationship of ASD use with fracture risk in children and young adults. RESULTS: Six studies reporting the outcomes of more than 900,000 children and young adults with ASD use were included in the meta-analysis. The pooled RR for fracture with the use of proton pump inhibitors (PPIs) versus non-use of these medications was 1.17 (95% CI = 1.1-1.25; P < 0.001) in children and 1.2 (95% CI = 0.87-1.65; P = 0.272) in young adults. By contrast, the use of histamine H2-receptor antagonists (H2RAs) was not significantly associated with fracture risk in children (RR, 1.08, 95% CI = 0.99-1.17; P = 0. 083) or young adults (RR, 1.08, 95% CI = 0.82-1.42; P = 0.589). Significant statistical and clinical heterogeneity among studies were determined for the main analysis and most of the subgroup analyses. CONCLUSIONS: Our study provides evidence linking PPI use to an increased risk of fracture in children. Thus, the use of PPIs in these patients should be carefully considered. However, randomized controlled studies are needed to determine causality and the role of unmeasured/residual confounding factors in this association.

Extracorporeal Shock Wave Therapy Combined with Complex Decongestive Therapy in Patients with Breast Cancer-Related Lymphedema: A Systemic Review and Meta-Analysis.

Breast cancer-related lymphedema (BCRL) is one of the most significant complications seen after surgery. Several studies demonstrated that extracorporeal shock wave therapy (ESWT), in addition to conventional complex decongestive therapy (CDT), had a positive effect on BCRL in various aspects. The systematic review and meta-analysis aim to explore the effectiveness of ESWT with or without CDT on BRCL patients. We searched PubMed, Embase, PEDro, Cochrane Library Databases, and Google Scholar for eligible articles and used PRISMA2020 for paper selection. Included studies were assessed by the PEDro score, Modified Jadad scale, STROBE assessment, and GRADE framework for the risk of bias evaluation. The primary outcomes were the volume of lymphedema and arm circumference. Secondary outcome measures were skin thickness, shoulder joint range of motion (ROM), and an impact on quality-of-life questionnaire. Studies were meta-analyzed with the mean difference (MD). Eight studies were included in the systemic review and four in the meta-analysis. In summary, we found that adjunctive ESWT may significantly improve the volume of lymphedema (MD = -76.44; 95% CI: -93.21, -59.68; p < 0.00001), skin thickness (MD = -1.65; 95% CI: -3.27, -0.02; p = 0.05), and shoulder ROM (MD = 7.03; 95% CI: 4.42, 9.64; p < 0.00001). The evidence level was very low upon GRADE appraisal. ESWT combined with CDT could significantly improve the volume of lymphedema, skin thickness, and shoulder ROM in patients with BCRL. There is not enough evidence to support the use of ESWT as a replacement for CDT. This study was registered with PROSPERO: CRD42021277110.

Efficacy and safety of mycophenolate mofetil in the treatment for IgA nephropathy: a meta-analysis of randomized controlled trials.

AIM: IgA nephropathy is virtually known as the most common glomerulopathy to end-stage renal failure in the world. Mycophenolate mofetil is a selective immunosuppressant widely used in organ transplantation, yet its tolerance and effectiveness in IgAN is controversial. METHODS: This is a systematic review and random-effects meta-analysis, searching PubMed, Embase, Te Cochrane Library, Science Citation Index, Ovid evidence-based medicine, Chinese Biomedical Literature and Chinese Science and Technology Periodicals. Screen out randomized controlled trials on patients with biopsy-proven IgA nephropathy and analysis mycophenolate mofetil treatment regimens used for therapy of IgA nephropathy. Complete remission and partial remission, doubling of creatinine level, proteinuria, incidence of end-stage kidney disease, infection, Cushing syndrome, diabetes, hepatic dysfunction or gastrointestinal symptoms, neurologic or visual ambiguity, acne, and alopecia were observed. RESULTS: Nine relevant trials were conducted with 587 patients enrolled. In Mycophenolate mofetil or plus medium/low-dose steroid comparing full-dose steroid alone or placebo, there was no significant difference. The risk of Cushing syndrome and diabetes had been significantly lowered with Mycophenolate mofetil-treated patients, while the risk of infection had been increased. CONCLUSIONS: Mycophenolate mofetil therapy did not differ in reducing proteinuria and Scr in patients with IgAN who had persistent proteinuria, while having fewer Cushing syndrome and diabetes risk and more infection risk. However, larger randomized studies are needed to reveal these results.

Patient characteristics, treatment patterns, and clinical outcomes among patients with previously treated recurrent or metastatic cervical cancer: A community oncology-based analysis.

OBJECTIVE: There is no standard systemic treatment for recurrent or metastatic cervical cancer (r/mCC) after failure of first-line (1L) therapy. This study characterizes the patient experience, treatment patterns, and clinical outcomes of patients who initiated second-line (2L) therapy for r/mCC in a US community oncology setting. METHODS: This is an observational study of cervical cancer patients who failed 1L systemic treatment for r/mCC and initiated 2L systemic therapy between 2014 and 2019 within the US Oncology Network (USON). USON's electronic health records were used to identify eligible patients and abstract data. Overall survival (OS), time to treatment discontinuation (TTD), and time to first subsequent treatment (TFST) were estimated using Kaplan-Meier methods. RESULTS: A total of 130 patients were identified (mean age 53 years). Over 60% of patients had Eastern Cooperative Oncology Group score of 0-1. Cytotoxic monotherapy was the most frequently prescribed regimen (N = 60, 46%) in 2L, followed by combination therapies (N = 45, 35%), pembrolizumab monotherapy (N = 19, 15%), and bevacizumab monotherapy (N = 6, 5%). Median OS was 9.1 months (95% CI: 7.2-12.2) after initiation of 2L therapy. Median TTD was 2.8 months (95% CI: 2.5-3.3), and median TFST was 4.9 months (95% CI: 4.2-5.7). No significant difference in outcomes was found when stratified by 2L treatments. CONCLUSIONS: The observed heterogeneity in 2L r/mCC therapy suggests no clear standard-of-care in this setting. Additionally, short duration of OS observed was consistent across 2L regimens. New, effective treatment options in this setting are needed.

Analyzing the potential therapeutic mechanism of Huashi Baidu Decoction on severe COVID-19 through integrating network pharmacological methods.

BACKGROUND AND AIM: Huashi Baidu Decoction (HSBD) is a novel complex prescription which has positive effects on severe COVID-19. This study was aimed to discover key Chinese materia medica, main active compounds, hub therapeutic target proteins and core signal pathways in the potential therapeutic mechanism of HSBD on severe COVID-19 through integrating network pharmacological methods. EXPERIMENTAL PROCEDURE: TCMSP, TCMID and STITCH databases were used to screen out active compounds and target proteins of HSBD. GeneCards database was used to screen out disease genes of severe COVID-19. The potential therapeutic targets of HSBD on severe COVID-19 were used to construct protein-protein interaction network through STRING database and the hub target proteins were discovered. Next, GO and KEGG enrichment analysis were carried out to discover core signal pathways. Finally, the network diagram of "Chinese materia medica-active compounds-therapeutic target proteins" was built, then key Chinese materia medica and main active compounds were selected. RESULTS AND CONCLUSION: HSBD might treat severe COVID-19 through 45 potential target genes, among them, there were 13 hub target genes: RELA, TNF, IL6, IL1B, MAPK14, TP53, CXCL8, MAPK3, MAPK1, IL4, MAPK8, CASP8, STAT1. Meanswhile, GO_BiologicalProcess and KEGG signaling pathways analysis results showed that the core signal pathways were inflammation and immune regulation pathways. Finally, 4 key Chinese materia medica and 11 main active compounds were discovered in the HSBD. In conclusion, the therapeutic mechanism of HSBD on severe COVID-19 might involve its pharmacological effects of anti-inflammation and immune regulation via acting on 45 disease-related proteins of severe COVID-19. TAXONOMY CLASSIFICATION BY EVISE: Viral Pneumonia, COVID-19, Acute Respiratory Distress Syndrome, Septic Shock, Chinese Herbal Medicine.

The Study of Yin-Chen-Hao-Tang Preventing and Treating Alcoholic Fatty Liver Disease through PPAR Signaling Pathway Based on Network Pharmacology and RNA-Seq Transcriptomics.

BACKGROUND: Alcoholic fatty liver disease (AFLD) is the first stage of the alcoholic liver disease course. Yin-Chen-Hao-Tang (YCHT) has a good clinical effect on the treatment of AFLD, but its molecular mechanism has not been elucidated. In this study, we tried to explore the molecular mechanism of YCHT in improving hepatocyte steatosis in AFLD mice through network pharmacology and RNA sequencing (RNA-Seq) transcriptomics. METHODS: Network pharmacological methods were used to analyze the potential therapeutic signaling pathways and targets of YCHT on AFLD. Then, the AFLD mice model was induced and YCHT was administered concurrently. Liver injury was measured by serum alanine aminotransferase (ALT) activity and liver tissue H&E staining, and liver steatosis was determined by serum triglyceride (TG) level and liver tissue Oil Red staining. The molecular mechanism of YCHT on prevention and treatment of mice AFLD was investigated according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differential expression genes data obtained by liver tissue RNA-Seq. Finally, ethanol-induced AFLD AML12 hepatocyte model was established, YCHT with or without PPARα agonist pemafibrate or PPARγ inhibitor GW9662 was administered, Nile Red fluorescent staining was used to evaluate steatosis levels in AML12 hepatocytes, and qRT-PCR was used to detect PPARα and PPARγ gene expression. RESULTS: The results of network pharmacology analysis showed that YCHT may exert its pharmacological effect on AFLD through 312 potential targets which are involved in many signaling pathways including the PPAR signaling pathway. AFLD mice experiments results showed that YCHT markedly decreased mice serum ALT activity and serum TG levels. YCHT also significantly improved alcohol-induced hepatic injury and steatosis in mice livers. Furthermore, KEGG pathway enrichment results of RNA-Seq showed that the PPAR signaling pathway should be the most relevant pathway of YCHT in the prevention and treatment of AFLD. AFLD hepatocyte model experiment results showed that YCHT could remarkably reduce hepatocyte steatosis through reducing PPARγ expression and increasing PPARα expression. CONCLUSIONS: Our study discovered that PPARγ and PPARα are the key targets and the PPAR signaling pathway is the main signaling pathway for YCHT to prevent and treat AFLD.