Drebrin promotes lung adenocarcinoma cell migration through inducing integrin ß1 endocytosis.

Lung adenocarcinoma (LUAD) is the most common type of lung cancers, which remains the leading cause of cancer-related death worldwide. Drebrin can promote cell migration and invasion with poor prognosis, but its roes in LUAD tumor progression remains unknown. We showed that the expression of Drebrin was upregulated in clinical LUAD samples. A Kaplan-Meier survival analysis showed that a high expression of Drebrin predicated poor prognosis in LUAD. In vitro, Drebrin promoted anchorage-independent growth and migration of LUAD cells. Drebrin interacted with dynamin through CT domain, and served as an adaptor to promote LUAD cell migration through inducing integrin ß1 endocytosis. Thus, this study demonstrated the critical role of Drebrin in LUAD and associated mechanism.

Obesity enhances the response to neoadjuvant anti-PD1 therapy in oral tongue squamous cell carcinoma.

OBJECTIVES: Previous studies have demonstrated that obesity may impact the efficacy of anti-PD1 therapy, but the underlying mechanism remains unclear. In this study, our objective was to determine the prognostic value of obesity in patients with oral tongue squamous cell carcinoma (OTSCC) treated with pembrolizumab and establish a subtype based on fatty acid metabolism-related genes (FAMRGs) for immunotherapy. MATERIALS AND METHODS: We enrolled a total of 56 patients with OTSCC who underwent neoadjuvant anti-PD1 therapy. Univariate and multivariate Cox regression analyses, Kaplan-Meier survival analysis, and immunohistochemistry staining were performed. Additionally, we acquired the gene expression profiles of pan-cancer samples and conducted GSEA and KEGG pathway analysis. Moreover, data from TCGA, MSigDB, UALCAN, GEPIA and TIMER were utilized to construct the FAMRGs subtype. RESULTS: Our findings indicate that high Body Mass Index (BMI) was significantly associated with improved PFS (HR = 0.015; 95% CI, 0.001 to 0.477; p = 0.015), potentially attributed to increased infiltration of PD1 + T cells. A total of 91 differentially expressed FAMRGs were identified between the response and non-response groups in pan-cancer patients treated with immunotherapy. Of these, 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) were found to affect PD-1 expression and T cell infiltration in HNSCC, which may impact the efficacy of anti-PD1 therapy. CONCLUSION: This study demonstrates that obesity serves as a robust prognostic predictor for patients with OTSCC undergoing neoadjuvant anti-PD1 therapy. Furthermore, the expression of 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) plays a pivotal role in the context of anti-PD1 therapy and deserves further investigation.

The Impact of Antithrombotic Medications on Postoperative Bleeding Events Following Hemorrhoidectomy.

BACKGROUND: Bleeding complications are a risk associated with hemorrhoid procedures. Despite the prevalence of anticoagulant and antiplatelet therapies, including newer direct oral anticoagulants (DOACs) in the aging patient population there is a paucity of data regarding the impact of the use of antithrombotic therapy (AT) especially DOACs, on bleeding complications of hemorrhoid procedures. METHODS: We retrospectively reviewed charts of patients who had undergone a total of 1152 procedures, including hemorrhoid excision and ligation, at a single institution in the years 2016-2018. We noted whether they were prescribed AT, the indication for therapy, perioperative medication management, whether a PBE occurred, and how the PBE was managed. RESULTS: PBE's were noted in 5.92% of patients on ATs, as opposed to 2.66% of patients not on ATs (P = .014.) The odds ratio of having a PBE when on ATs vs not on ATs is 2.3 (95% CI 1.21 to 4.38, P = .011). Seven out of 40 (17.5%) total PBE's required hospital admission or repeat procedure, and this was not associated with AT use. Surprisingly, although males represented most of the patients on ATs, females were statistically more likely to have a PBE following a hemorrhoidectomy if on ATs. DISCUSSION: Patients on AT have an elevated risk of PBE compared to patients not on AT. No significant difference was found between the two groups when considering only those PBE's severe enough to require hospital admission or repeat procedure. Further research is required to establish clear guidelines regarding the perioperative management of AT for hemorrhoid procedures.

Intrathoracic plates versus extrathoracic plates: a comparison of postoperative pain in surgical stabilization of rib fracture technique.

Background: Surgical stabilization of rib fractures (SSRF) has been shown to improve outcomes, yet there is an absence of studies comparing SSRF techniques. An intrathoracic system that minimizes incision length has recently been developed and adopted by multiple institutions. We hypothesized that SSRF with an intrathoracic system plus intercostal nerve cryoneurolysis (IC) leads to improved pain control compared with an extrathoracic system plus IC. Methods: A single-center, retrospective chart review was performed comparing intrathoracic SSRF versus extrathoracic SSRF, and included patients undergoing SSRF from 2015 to 2021 at a level 1 trauma center. Patients who did not undergo intercostal nerve cryoablation were excluded. The primary outcome was opioid consumption based on morphine milligram equivalent (MME) consumption. We collected Rib score, Blunt Pulmonary Contusion 18 Score, number of rib fractures, number of ribs plated, and Injury Severity Score (ISS) to compare baseline characteristics of each group. Results: A total of 112 patients were evaluated for study inclusion. Thirty-one patients were excluded due to missing outcomes data and/or lack of cryoablation. There was no difference in ISS or Rib Score between the intrathoracic (n=33) and extrathoracic (n=48) groups. At 7-day follow-up, the median MME requirement was significantly lower in the intrathoracic group (21.25) versus the extrathoracic group (46.20) (p=0.02). Conclusion: Intrathoracic SSRF was associated with a lower postoperative MME consumption compared with extrathoracic SSRF. These data support the use of intrathoracic SSRF to improve pain control compared to extrathoracic SSRF. Level of evidence: III.

Variation in Care of Well-Appearing Hypothermic Young Infants: A Multisite Study.

BACKGROUND AND OBJECTIVES: Numerous decision tools have emerged to guide management of febrile infants, but limited data exist to guide the care of young infants presenting with hypothermia. We evaluated the variation in care for well-appearing hypothermic young infants in the hospital and/or emergency department setting between participating sites. METHODS: This is a retrospective cohort study of well-appearing infants ≤90 days old across 9 academic medical centers from September 1, 2016 to May 5, 2021. Infants were identified via billing codes for hypothermia or an initial temperature ≤36.0°C with manual chart review performed. Primary outcomes included assessment of variation in diagnostic evaluation, disposition, empirical antimicrobial therapy, and length of stay. RESULTS: Of 14 278 infants originally identified, 739 met inclusion criteria. Significant interhospital variation occurred across all primary outcomes. Across sites, a full serious bacterial illness evaluation was done in 12% to 76% of hypothermic infants. Empirical antibiotics were administered 20% to 87% of the time. Performance of herpes simplex viral testing ranged from 7% to 84%, and acyclovir was empirically started 8% to 82% of the time. Hospital admission rates ranged from 45% to 100% of patients. CONCLUSIONS: Considerable variation across multiple aspects of care exists for well-appearing young infants presenting with hypothermia. An improved understanding of hypothermic young infants and their risk of infection can lead to the development of clinical decision tools to guide appropriate evaluation and management.

Too Much Too Late? Chemotherapy Administration at the End of Life: A Retrospective Observational Study.

PURPOSE: Cancer treatment for those nearing death has become increasingly aggressive over time despite evidence that less aggressive approaches are associated with better quality of life and sometimes longer survival. Chemotherapy administration in the last 14 days of life is one of the proposed benchmarks for quality of cancer care. The purpose of our study is to evaluate factors associated with aggressive cancer treatment in patients who died within 2 weeks of receiving chemotherapy. METHODS: This retrospective cohort study evaluated adult patients who died between 1 February 2018 and 1 March 2019 after receiving cancer treatment in the preceding 14 days at the Prisma Health Cancer Institute. This project was approved by our institutional review board. Data was obtained by review of electronic medical records and analyzed using commercial software. RESULTS: We identified 92 patients who met inclusion criteria for the study. Of those who were staged, 57% had metastatic disease. A majority received treatments with only palliative intent (54%). These patients overwhelmingly died in the hospital (62%). Few had documented advanced directives (28%) or dedicated palliative care for longer than 1 week (28%). Overall, this cohort reflects a rate of 11.7% of patients who received cancer treatment during the study time period. SIGNIFICANCE OF RESULTS: Patients receiving aggressive cancer treatment at the end of life elucidate significant gaps in quality cancer care, particularly the early involvement of dedicated palliative care. Systematic review helped identify multiple gaps and assisted in implementing interventions to improve this outcome.

Attitudes, beliefs and behaviors of religiosity, spirituality, and cultural competence in the medical profession: A cross-sectional survey study.

INTRODUCTION: Religion and spirituality play important roles in the lives of many, including healthcare providers and their patients. The purpose of this study was to examine the relationships between religion, spirituality, and cultural competence of healthcare providers. METHODS: Physicians, residents, and medical students were recruited through social platforms to complete an electronically delivered survey, gathering data regarding demographics, cultural competency, religiosity, and spirituality. Four composite variables were created to categorize cultural competency: Patient Care Knowledge, Patient Care Skills/Abilities, Professional Interactions, and Systems Level Interactions. Study participants (n = 144) were grouped as Christian (n = 95)/non-Christian (n = 49) and highly religious (n = 62)/not highly religious (n = 82); each group received a score in the four categories. Wilcoxon rank sum and Chi-square tests were used for analysis of continuous and discrete variables. RESULTS: A total of 144 individuals completed the survey with the majority having completed medical school (n = 87), identifying as women (n = 108), white (n = 85), Christian (n = 95), and not highly religious (n = 82). There were no significant differences amongst Christian versus non-Christian groups or highly religious versus not highly religious groups when comparing their patient care knowledge (p = .563, p = .457), skills/abilities (p = .423, p = .51), professional interactions (p = .191, p = .439), or systems level interaction scores (p = .809, p = .078). Nevertheless, participants reported decreased knowledge of different healing traditions (90%) and decreased skills inquiring about religious/spiritual and cultural beliefs that may affect patient care (91% and 88%). Providers also reported rarely referring patients to religious services (86%). CONCLUSIONS: Although this study demonstrated no significant impact of healthcare providers' religious/spiritual beliefs on the ability to deliver culturally competent care, it did reveal gaps around how religion and spirituality interact with health and healthcare. This suggests a need for improved cultural competence education.

Exercise Counseling in Pregnancy: Do Women Perceive Receiving the Information They Need?

The American College of Obstetricians and Gynecologists recommends that women exercise throughout pregnancy unless they have a condition-related contraindication. This study's purpose was to determine if pregnant women perceive receiving exercise counseling by their providers with details of frequency, intensity, type, and time (FITT principle). Women in 2 postpartum care units of a large health care system were invited to complete a voluntary, anonymous survey regarding whether they received exercise counseling during their prenatal care. Survey results were descriptively reported, stratified by demographic variables, and analyzed using Fisher's exact tests. Of 224 postpartum women surveyed, 130 (58.0%) perceived receiving exercise counseling during pregnancy; 119 (91.5%) did not recall receiving counseling on exercise frequency. Though 165 (73.6%) exercised before becoming pregnant, 64 (38.8%) ceased exercise during pregnancy. Eighty-eight (39.3%) received advice from other sources/non-health care professionals. Privately insured women reported receiving exercise counseling at a higher rate (70.1%) than those on Medicaid (44.8%) or uninsured (40.0%; P = .004). A disproportionate number of pregnant women perceived not receiving adequate prenatal exercise counseling or received incomplete counseling. Women at a socioeconomic disadvantage may be vulnerable. As social determinants of health, structural barriers, and socioeconomic status likely contribute, women may benefit from more targeted inclusive and equitable messaging.

PMEPA1 Is a Prognostic Biomarker That Correlates With Cell Malignancy and the Tumor Microenvironment in Bladder Cancer.

Prostate transmembrane protein androgen induced 1 (PMEPA1) has been reported to promote cancer progression, but the potential role of PMEPA1 in bladder cancer (BLCA) remains elusive. We assess the role of PMEPA1 in BLCA, via a publicly available database and in vitro study. PMEPA1 was identified from 107 differentially expressed genes (DEGs) to have prognostic value. GO, KEGG, and GSEA analysis indicated that PMEPA1 was involved in cancer progression and the tumor microenvironment (TME). Then bioinformatical analysis in TCGA, GEO, TIMER, and TISIDB show a positive correlation with the inflammation and infiltration levels of three tumor-infiltrating immune cells (TAMs, CAFs, and MDSCs) and immune/stromal scores in TME. Moreover, in vitro study revealed that PMEPA1 promotes bladder cancer cell malignancy. Immunohistochemistry and survival analysis shed light on PMEPA1 potential to be a novel biomarker in predicting tumor progression and prognosis. At last, we also analyzed the role of PMEPA1 in predicting the molecular subtype and the response to several treatment options in BLCA. We found that PMEPA1 may be a novel potential biomarker to predict the progression, prognosis, and molecular subtype of BLCA.

Suppression of DLBCL Progression by the E3 Ligase Trim35 Is Mediated by CLOCK Degradation and NK Cell Infiltration.

The majority of diffuse large B-cell lymphoma (DLBCL) patients develop relapsed or refractory disease after standard ruxolitinib, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, which is partly related to a dysregulated tumor immune microenvironment. However, how the infiltration of immune cells is appropriately regulated is poorly understood. Herein, we show that the E3 ubiquitin ligase Trim35 is expressed at low levels in human DLBCL tissues. We also show that overexpression of Trim35 suppresses DLBCL cell proliferation and correlates with inferior survival in DLBCL patients. Our mechanistic study shows that Trim35 functions as an E3 ligase to mediate the ubiquitination and degradation of CLOCK, a key regulator of circadian rhythmicity. High expression of Trim35 correlates with NK cell infiltration in DLBCL, partly due to the degradation of CLOCK. Consistently, patients with high expression of CLOCK show poor overall survival. Overall, these findings suggest that Trim35 suppresses the progression of DLBCL by modulating the tumor immune microenvironment, indicating that it may be a promising diagnostic and prognostic biomarker in DLBCL.