Decision aids for promoting shared decision-making: A review of systematic reviews.

In the context of shared decision-making (SDM), experts have advocated the use of validated decision aids (DAs) as valuable tools for facilitating SDM in various healthcare scenarios. This comprehensive review attempts to analyze a vast corpus of DA research by performing thorough searches across four prominent databases (PubMed, CINAHL, Embase, and Web of Science). Independent reviewers selected relevant reviews, extracted data, and assessed review quality using the AMSTAR II tool. A total of 34 systematic reviews were identified and evaluated in this review, encompassing a wide range of outcomes associated with using DAs. These outcomes include patient knowledge, patient involvement in SDM, decision conflict, decision regret, satisfaction, and adherence. In addition, DAs positively affect healthcare provider outcomes by increasing satisfaction, reducing decision conflicts, and lengthening clinical consultations. This review highlights the need for additional research in specific contexts such as long-term care, mental health, and reproductive health to better understand the benefits and challenges of implementing DAs in these settings. Such research can contribute to the improvement of SDM practices and patient-centered care.

Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results.

BACKGROUND & AIMS: SERENE UC (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Ulcerative Colitis) evaluated the efficacy of higher adalimumab induction and maintenance dose regimens in patients with ulcerative colitis. METHODS: This phase 3, double-blind, randomized trial included induction and maintenance studies, with a main study (ex-Japan) and Japan substudy. Eligible patients (18-75 years, full Mayo score 6-12, centrally read endoscopy subscore 2-3) were randomized 3:2 to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3) or standard induction regimen (160 mg at week 0 and 80 mg at week 2); all received 40 mg at weeks 4 and 6. At week 8, all patients were rerandomized 2:2:1 (main study) to 40 mg every week (ew), 40 mg every other week (eow), or exploratory therapeutic drug monitoring; or 1:1 (Japan substudy) to 40 mg ew or 40 mg eow maintenance regimens. RESULTS: In the main study, 13.3% vs 10.9% of patients receiving the higher induction regimen vs standard induction regimen achieved clinical remission (full Mayo score ≤2 with no subscore >1) at week 8 (induction primary end point; P = .265); among week-8 responders, 39.5% vs 29.0% receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (maintenance primary end point; P = .069). In the integrated (main + Japan) population, 41.1% vs 30.1% of week-8 responders receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (nominal P = .045). Safety profiles were comparable between dosing regimens. CONCLUSION: Although primary end points were not met, a >10% absolute difference in clinical remission was demonstrated with higher adalimumab maintenance dosing. Higher dosing regimens were generally well tolerated and consistent with the known safety profile of adalimumab in ulcerative colitis. CLINICALTRIALS: gov, Number: NCT002209456.

Higher vs Standard Adalimumab Induction Dosing Regimens and Two Maintenance Strategies: Randomized SERENE CD Trial Results.

BACKGROUND & AIMS: Dose-optimization strategies for biologic therapies in Crohn's disease (CD) are not well established. The SERENE CD (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Crohn's Disease) trial evaluated higher vs standard adalimumab induction dosing and clinically adjusted (CA) vs therapeutic drug monitoring (TDM) maintenance strategies in patients with moderately to severely active CD. METHODS: In this phase 3, randomized, double-blind, multicenter trial, eligible adults (Crohn's Disease Activity Index score of 220-450, endoscopic evidence of mucosal inflammation, and previous failure of standard therapies) were randomized to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3; n = 308) or standard induction regimen (adalimumab 160 mg at week 0 and 80 mg at week 2; n = 206) followed by 40 mg every other week from week 4 onward. Co-primary end points included clinical remission at week 4 and endoscopic response at week 12. At week 12, patients were re-randomized to maintenance therapy optimized by Crohn's Disease Activity Index and C-reactive protein (CA; n = 92) or serum adalimumab concentrations and/or clinical criteria (TDM; n = 92); exploratory end points were evaluated at week 56. RESULTS: Similar proportions of patients receiving higher induction regimen and standard induction regimen achieved clinical remission at week 4 (44% in both; P = .939) and endoscopic response at week 12 (43% vs 39%, respectively, P = .462). Week 56 efficacy was similar between CA and TDM. Safety profiles were comparable between dosing regimens. CONCLUSIONS: Higher induction regimen was not superior to standard induction regimen, and CA and TDM maintenance strategies were similarly efficacious. Adalimumab therapy was well tolerated, and no new safety concerns were identified. (ClinicalTrials.gov, Number: NCT02065570).

A Multicenter Study of Clinicopathology and Immunohistochemical Distinction between Adult and Pediatric Large B-Cell Lymphoma.

Introduction: Pediatric DLBCL is considered a homogenous group and has superior outcomes compared to adults. This study investigated the clinical pathology and immunohistochemical distinction between adult and pediatric large B-cell lymphoma. Methods: A cross-sectional study of 314 NHLs with the morphology of diffuse pattern, large B-cell, and CD20 expression was investigated. Results: Of 314 cases, there were 6 cases of pleomorphic MCL (all in adults), 19 cases of Burkitt lymphoma (all in children), and 289 cases of DLBCL. Pediatric DLBCL had many striking differences: More frequency in extra-nodal sites; a higher proportion of centroblastic morphology; a predominance of GCB-type; a high proliferation rate; an infrequency of Bcl2 protein expression, and a lack of double-expresser lymphoma. Conclusions: Our study demonstrated the significant biological differences between adult and pediatric DLBCL.

Reproductive biology research down under: highlights from the Australian and New Zealand Annual Meeting of the Society for Reproductive Biology, 2021.

Against the backdrop of a global pandemic, the Society for Reproductive Biology (SRB) 2021 meeting reunited the Australian and New Zealand reproductive research community for the first time since 2019 and was the first virtual SRB meeting. Despite the recent global research disruptions, the conference revealed significant advancements in reproductive research, the importance of which span human health, agriculture, and conservation. A core theme was novel technologies, including the use of medical microrobots for therapeutic and sperm delivery, diagnostic hyperspectral imaging, and hydrogel condoms with potential beyond contraception. The importance of challenging the contraceptive status quo was further highlighted with innovations in gene therapies, non-hormonal female contraceptives, epigenetic semen analysis, and in applying evolutionary theory to suppress pest population reproduction. How best to support pregnancies, particularly in the context of global trends of increasing maternal age, was also discussed, with several promising therapies for improved outcomes in assisted reproductive technology, pre-eclampsia, and pre-term birth prevention. The unique insights gained via non-model species was another key focus and presented research emphasised the importance of studying diverse systems to understand fundamental aspects of reproductive biology and evolution. Finally, the meeting highlighted how to effectively translate reproductive research into policy and industry practice.

Nuclear Receptors in Ovarian Function.

The ovary undergoes cycles of hormone production that regulate physiological changes necessary for folliculogenesis, ovulation and luteinisation, ultimately contributing to female reproductive success. Crucial to these biological processes is stage-specific nuclear receptor signalling. While the transcriptional regulatory roles of steroid receptors in female fertility and especially ovarian functions have long been documented, non-steroid receptors also play an important part in regulating gene expression at various stages of ovarian development. The recent application of high-throughput genomic and transcriptomic technologies has begun to shed light on the molecular mechanisms underlying ovarian nuclear receptor actions and pointed to a complex interplay between highly specific transcription co-regulators as well as between nuclear receptors in mediating mutual as well as unique target genes. Interrelationships between nuclear receptors as well as the involvement of context-specific protein and non-protein co-regulators are likely keys to the precise and specific nuclear receptor action in the ovary. Leveraging such knowledge on the nuclear receptor network is especially valuable in the development of novel fertility treatments as well as female contraceptives.

Cerebrolysin for stroke, neurodegeneration, and traumatic brain injury: review of the literature and outcomes.

Cerebrolysin therapy has the potential to significantly aid in the treatment of a wide variety of debilitating neurological diseases including ischemic strokes, neurodegenerative disorders, and traumatic brain injuries. Although Cerebrolysin is not approved for use in the USA, it is used clinically in over 50 countries worldwide. In this review, we focus on outlining the role that Cerebrolysin has in stimulating the molecular signaling pathways that are critical for neurological regeneration and support. An extensive evaluation of these signaling pathways reveals that Cerebrolysin has the potential to intervene in a diverse array of pathophysiological causes of neurological diseases. In the clinical setting, Cerebrolysin is generally safe for human use and has provided functional improvement when used as an adjunct treatment. However, our literature review revealed inconsistent results, as several clinical studies suggested that Cerebrolysin treatment has minor clinical relevance and did not have significant advantages over a placebo. In conclusion, we found that Cerebrolysin therapy can potentially play a major role in the treatment of many neurological diseases. Nevertheless, there remains much to be elucidated about the efficacy of this treatment for specific neurological conditions, and more robust clinical data is needed to reach a consensus and properly define the therapeutic role of Cerebrolysin.

Differential capacity of CD90+ cells in autophagy activation following chemotherapy in hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: Analysis of cancer biomarkers is an important tool in developing targeted-therapy and in modulating chemoresistance. Here, we analyze the relevance of CD90, a marker of cancer stem cells (CSC) in hepatocellular carcinoma (HCC) and its correlation with autophagy. MATERIALS AND METHODS: For in vivo study, 86 specimens were collected from 43 patients undergoing liver resections. In each patient, HCC nodule (HCC) and surrounding non-tumor (SNT) were collected. For in vitro study, HCC cells JHH6 subpopulations expressing CD90+ and CD90- were isolated using magnetic-sorter and confirmed by flow-cytometry. Upon doxorubicin treatment, autophagy turn-over was analyzed by RTqPCR for mRNA expression, Western blot for protein expression, and autophagosome staining for autophagy-flux. Cytotoxicity test was performed by MTT assay. Gene and protein analysis were performed in clinical samples together with immunohistostaining. RESULTS: CD90 mRNA expression was higher in HCC than in SNT for 8-fold (p < 0.001). LC3-II protein was up-regulated in the HCC in comparison with the SNT (p < 0.05). In vitro model showed that CD90+ and CD90- cells had diverse expressions of autophagy-related genes. Upon doxorubicin treatment, autophagy was activated in both cells by increasing LC3-II protein expression, autophagic vacuoles, and dysregulation of autophagy-related mRNAs. A differential autophagic capacity was noticed between two subpopulations and it was correlated with cellular toxicity assay. CONCLUSIONS: We demonstrated the relevance of differential autophagy capacity of CD90+ cells in HCC. Autophagy was involved in cancer-defense mechanism against doxorubicin. Cancer promoting function of autophagy in CD90+ cells was also related to cancer environment.

Toward a robust tool for pharmacokinetic-based personalization of treatment with tacrolimus in solid organ transplantation: A model-based meta-analysis approach.

AIMS: The objective of this study is to develop a generic model for tacrolimus pharmacokinetics modelling using a meta-analysis approach, that could serve as a first step towards a prediction tool to inform pharmacokinetics-based optimal dosing of tacrolimus in different populations and indications. METHODS: A systematic literature review was performed and a meta-model developed with NONMEM software using a top-down approach. Historical (previously published) data were used for model development and qualification. In-house individual rich and sparse tacrolimus blood concentration profiles from adult and paediatric kidney, liver, lung and heart transplant patients were used for model validation. Model validation was based on successful numerical convergence, adequate precision in parameter estimation, acceptable goodness of fit with respect to measured blood concentrations with no indication of bias, and acceptable performance of visual predictive checks. External validation was performed by fitting the model to independent data from 3 external cohorts and remaining previously published studies. RESULTS: A total of 76 models were found relevant for meta-model building from the literature and the related parameters recorded. The meta-model developed using patient level data was structurally a 2-compartment model with first-order absorption, absorption lag time and first-time varying elimination. Population values for clearance, intercompartmental clearance, central and peripheral volume were 22.5 L/h, 24.2 L/h, 246.2 L and 109.9 L, respectively. The absorption first-order rate and the lag time were fixed to 3.37/h and 0.33 hours, respectively. Transplanted organ and time after transplantation were found to influence drug apparent clearance whereas body weight influenced both the apparent volume of distribution and the apparent clearance. The model displayed good results as regards the internal and external validation. CONCLUSION: A meta-model was successfully developed for tacrolimus in solid organ transplantation that can be used as a basis for the prediction of concentrations in different groups of patients, and eventually for effective dose individualization in different subgroups of the population.

Cumulative exposure to work-related traumatic events and current post-traumatic stress disorder in New York City's first responders.

BACKGROUND AND OBJECTIVES: Cumulative exposure to work-related traumatic events (CE) is a foreseeable risk for psychiatric disorders in first responders (FRs). Our objective was to examine the impact of work-related CE that could serve as predictor of posttraumatic stress disorder (PTSD) and/or depression in FRs. DESIGN: Cross-sectional examination of previous CE and past-month PTSD outcomes and depression in 209 FRs. METHODS: Logistic (probable PTSD; probable depression) and Poisson regressions (PTSD score) of the outcomes on work-related CE indexes, adjusting for demographic variables. Differences across occupational groups were also examined. Receiver operating characteristic analysis determined the sensitivity and specificity of CE indexes. RESULTS: All indexes were significantly and differently associated with PTSD; associations with depression were non-significant. The index capturing the sheer number of different incidents experienced regardless of frequency ('Variety') showed conceptual, practical and statistical advantages compared to other indexes. In general, the indexes showed poor to fair discrimination accuracy. CONCLUSIONS: Work-related CE is specifically associated with PTSD. Focusing on the variety of exposures may be a simple and effective strategy to predict PTSD in FRs. Further research on sensitivity and specificity of exposure indexes, preferably examined prospectively, is needed and could lead to early identification of individuals at risk.

Integrating Social Determinants of Health With Treatment and Prevention: A New Tool to Assess Local Area Deprivation.

We assessed the appropriate geographic scale to apply an area deprivation index (ADI), which reflects a geographic area's level of socioeconomic deprivation and is associated with health outcomes, to identify and screen patients for social determinants of health. We estimated the relative strength of the association between the ADI at various geographic levels and a range of hospitalization rates by using age-adjusted odds ratios in an 8-county region of New York State. The 10-km local ADI estimates had the strongest associations with all hospitalization rates (higher odds ratios) followed by estimates at 20 km, 30 km, and the regional scale. A locally sensitive ADI is an ideal measure to identify and screen for the health care and social services needs and to advance the integration of social determinants of health with clinical treatment and disease prevention.

Immunohistochemical expression in idiopathic inflammatory myopathies at a single center in Vietnam.

Background: The identification of idiopathic inflammatory myopathies (IIMs) requires a comprehensive analysis involving clinical manifestations and histological findings. This study aims to provide insights into the histopathological and immunohistochemical aspects of IIMs. Methods: This retrospective case series involved 56 patients diagnosed with IIMs at the Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, from 2019 to 2023. The histology and immunohistochemical expression of HLA-ABC, HLA-DR, C5b-9, Mx1/2/3, and p62 were detected. Results: We examined six categories of inflammatory myopathy, including immunemediated necrotizing myopathy (58.9%), dermatomyositis (DM; 23.2%), overlap myositis (8.9%), antisynthetase syndrome (5.4%), inclusion body myositis (IBM; 1.8%), and polymyositis (1.8%). The average age of the patients was 49.7 ± 16.1 years, with a female-to-male ratio of 3:1. Inflammatory cell infiltration in the endomysium was present in 62.5% of cases, perifascicular atrophy was found in 17.8%, and fiber necrosis was observed in 42 cases (75.0%). Rimmed vacuoles were present in 100% of cases in the IBM group. Immunohistochemistry showed the following positivity rates: HLA-ABC (89.2%), HLA-DR (19.6%), C5b-9 (57.1%), and Mx1/2/3 (10.7%). Mx1/2/3 expression was high in DM cases. p62 vacuole deposits were noted in the IBM case. The combination of membrane attack complex and major histocompatibility complex I helped detect IIMs in 96% of cases. Conclusions: The diagnosis of IIMs and their subtypes should be based on clinical features and histopathological characteristics. Immunohistochemistry plays a crucial role in the diagnosis and differentiation of these subgroups.

Efficacy and Safety of Upadacitinib or Elsubrutinib Alone or in Combination for Systemic Lupus Erythematosus: A Phase 2 Randomized Controlled Trial.

OBJECTIVE: The 48-week, phase 2 SLEek study (NCT03978520) evaluated the efficacy and safety of upadacitinib (Janus kinase inhibitor) and elsubrutinib (Bruton's tyrosine kinase inhibitor) alone or in combination (ABBV-599) in adults with moderately to severely active systemic lupus erythematosus (SLE). METHODS: Patients were randomized 1:1:1:1:1 to once-daily (QD) ABBV-599 high dose (HD; elsubrutinib 60mg + upadacitinib 30mg), ABBV-599 low dose (LD; elsubrutinib 60mg + upadacitinib 15mg), elsubrutinib 60mg, upadacitinib 30mg, or placebo. The primary endpoint was the proportion of patients achieving both SLE Responder Index-4 (SRI-4) and glucocorticoid dose ≤10mg QD at week 24. Additional assessments through week 48 included British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) and Lupus Low Disease Activity State (LLDAS) responses, number of flares, time to first flare, and adverse events. RESULTS: The study enrolled 341 patients. The ABBV-599LD and elsubrutinib arms were discontinued after a planned interim analysis showed lack of efficacy (no safety concerns). More patients achieved the primary endpoint with upadacitinib (54.8%; P=0.028) and ABBV-599HD (48.5%; P=0.081) versus placebo (37.3%). SRI-4, BICLA, and LLDAS response rates were higher for both upadacitinib and ABBV-599HD versus placebo at weeks 24 and 48. Flares were reduced and time to first flare through week 48 was substantially delayed with both upadacitinib and ABBV-599HD versus placebo. No new safety signals were observed beyond those previously reported for upadacitinib or elsubrutinib. CONCLUSIONS: Upadacitinib 30mg alone or in combination with elsubrutinib (ABBV-599HD) demonstrated significant improvements in SLE disease activity, reduced flares and were well tolerated through 48 weeks.

Pirfenidone affects human cardiac fibroblast proliferation and cell cycle activity in 2D cultures and engineered connective tissues.

The anti-fibrotic drug pirfenidone (PFD) is currently in clinical testing for the treatment of heart failure with preserved ejection fraction; however, its effects on human cardiac cells have not been fully investigated. Therefore, we aimed to characterize the impact of PFD on human cardiac fibroblasts (CF) in 2D culture as well as in 3D-engineered connective tissues (ECT). We analyzed proliferation by automated cell counting and changes in signaling by immunoblotting. We generated ECT with different geometries to modify the cellular phenotype and investigated the effects of PFD on cell number and viability as well as on cell cycle activity. We further studied its effect on ECT compaction, contraction, stiffening, and strain resistance by ECT imaging, pole deflection analysis, and ultimate tensile testing. Our data demonstrate that PFD inhibits human CF proliferation in a concentration-dependent manner with an IC50 of 0.43 mg/ml and its anti-mitogenic effect was further corroborated by an inhibition of MEK1/2, ERK1/2, and riboprotein S6 (rpS6) phosphorylation. In ECT, a lower cell cycle activity was found in PFD-treated ECT and fewer cells resided in these ECT after 5 days of culture compared to the control. Moreover, ECT compaction as well as ECT contraction was impaired. Consequently, biomechanical analyses demonstrated that PFD reduced the stiffness of ECT. Taken together, our data demonstrate that the anti-fibrotic action of PFD on human CF is based on its anti-mitogenic effect in 2D cultures and ECT.

PD-L1 and TILs expression and their association with clinicopathological characteristics in Vietnamese women with primary invasive breast cancer.

Tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are promising new factors in the prognosis and prediction of breast cancer patients. Our study evaluated the prevalence of expression of TILs on hematoxylin and eosin (H&E) slides, PD-L1 expression on immunohistochemistry, and their association with clinicopathological characteristics in Vietnamese women with invasive breast cancer. This study was conducted on 216 women with primary invasive breast cancer. The evaluation of TILs on the HE slides was based on the International TILs Working Group 2014 recommendation. PD-L1 protein expression was determined using the Combined Positive Score, the number of tumor cells, lymphocytes, and macrophages stained by PD-L1 divided by the total viable tumor cells multiplied by 100. Based on the cutoff of 11%, the prevalence of TILs expression was 35.6%, of which highly expressed TILs (≥50%) accounted for 15.3%. Postmenopausal women and those who had a body mass index of 25 kg/m2 or greater had a higher odds of having TILs expression. However, patients who had the expression of Ki-67, HER-positive molecular subtype, and triple-negative subtype were more likely to have TILs expression. The prevalence of PD-L1 expression was 30.1%. A significantly higher odds of having PD-L1 was found in patients who had a history of benign breast disease, self-detected tumor and had TILs expression. The expression of TILs and PD-L1 is common in Vietnamese women with invasive breast cancer. Because of the importance of these expressions, routine evaluation to find women who had TILs and PD-L1 is needed so that treatment and prognosis can be optimized. Such routine evaluation can be targeted to those who had a high-risk profile found in this study.

Concordance of Clinical, Histologic and Direct Immunofluorescence Findings in Patients with Autoimmune Bullous Dermatoses in Vietnam.

Introduction: Autoimmune bullous dermatoses (ABD) represent a heterogeneous group of blistering disorders that may be debilitating with high morbidity. Clinical, histological, and direct immunofluorescence (DIF) studies are essential in establishing an accurate diagnosis of ABD, which is essential for its clinical management. Our study objective was to perform a systematic evaluation of ABD cases in a patient population at an academic medical center in Ho Chi Minh City, Vietnam, and determine the degree of concordance of clinical, histological, and DIF findings in ABD. Methodology: A systematic retrospective cross-sectional study was performed on 92 patients diagnosed with ABD by clinical, histological, and DIF studies at the University of Medicine and Pharmacy in Ho Chi Minh City, Vietnam, between September 2019 and September 2021. The clinical histories, H and E stained tissue sections, and DIF stains were evaluated by pathologists at the University of Medicine and Pharmacy. Results: ABD was evaluated as a whole and subdivided into an intraepidermal blister subgroup and a subepidermal blister subgroup. The analysis of paired diagnostic methods (clinical, histological, and DIF) for concordance with the final diagnosis was performed and showed that there were no statistically significant differences between the paired methods (McNemar's test, p > 0.05). There was moderate concordance between the clinical, histological, and DIF diagnoses among all ABD cases (Brennan-Prediger coefficient Kappa test, κBP = 0.522, CI = 0.95). In the intraepidermal blister subgroup, the diagnostic accuracies of the histology and DIF stains were comparable to each other, and both were more accurate than a clinical diagnosis alone. In the subepidermal blister subgroup, there was no statistically significant difference in each pair of the three diagnostic methods (clinical, histological, and DIF) (McNemar's test, p > 0.05). The concordance between the clinical, histological, and DIF diagnoses was high for the intraepidermal blister subgroup (Kappa test, κBP = 0.758, CI = 0.95). However, the concordance between the clinical, histological, and DIF diagnoses was slight for the subepidermal blister subgroup (Kappa test, κBP = 0.171, CI = 0.95). Conclusion: Histological evaluation is highly accurate in the diagnosis of the intraepidermal blister subgroup, but it is not as accurate in the diagnosis of the subepidermal blister subgroup in the Vietnamese patient cohort in which clinical, histological, and DIF studies were performed. DIF stains are a crucial diagnostic tool for ABD in this patient population.

FAAH inhibition ameliorates breast cancer in a murine model.

Breast cancer is the leading cancer among females worldwide. Disease outcome depends on the hormonal status of the cancer and whether or not it is metastatic, but there is a need for more efficacious therapeutic strategies where first line treatment fails. In this study, Fatty Acid Amide Hydrolase (FAAH) inhibition and endocannabinoids were examined as therapeutic alternatives. FAAH is an integral membrane enzyme that hydrolyzes endocannabinoids, rendering them inactive, and FAAH inhibition is predicted to increase cancer cell death. To test this, breast cancer cells were probed for FAAH expression using Western blot analysis, treated with FAAH inhibitors, exogenous endocannabinoids, and combinations of the two treatments, and assessed for viability. High levels of FAAH were observed in different breast cancer cell lines. FAAH inhibition was more effective than exogenous endocannabinoid treatment, and the combination of FAAH inhibitors and endocannabinoids was the most effective in inducing apoptosis of breast cancer cells in vitro. In addition, in vivo FAAH inhibition reduced breast cancer growth in immunodeficient mice. FAAH inhibition is a promising approach, and tremendous progress has been made in the field to validate this mechanism as an alternative to chemotherapy. Further research exploring the therapeutic potential and impact of FAAH expression on cancer cells is warranted.

Coronavirus Disease 2019, Diabetes, and Inflammation: A Systemic Review.

People with cardiometabolic diseases [namely type 2 diabetes (T2D), obesity, or metabolic syndrome] are more susceptible to coronavirus disease 2019 (COVID-19) infection and endure more severe illness and poorer outcomes. Hyperinflammation has been suggested as a common pathway for both diseases. To examine the role of inflammatory biomarkers shared between COVID-19 and cardiometabolic diseases, we reviewed and evaluated published data using PubMed, SCOPUS, and World Health Organization COVID-19 databases for English articles from December 2019 to February 2022. Of 248 identified articles, 50 were selected and included. We found that people with diabetes or obesity have (i) increased risk of COVID-19 infection; (ii) increased risk of hospitalization (those with diabetes have a higher risk of intensive care unit admissions) and death; and (iii) heightened inflammatory and stress responses (hyperinflammation) to COVID-19, which worsen their prognosis. In addition, COVID-19-infected patients have a higher risk of developing T2D, especially if they have other comorbidities. Treatments controlling blood glucose levels and or ameliorating the inflammatory response may be valuable for improving clinical outcomes in these patient populations. In conclusion, it is critical for health care providers to clinically evaluate hyperinflammatory states to drive clinical decisions for COVID-19 patients.

Bellevue Hospital, the Oldest Public Health Center in the United States of America.

Bellevue Hospital is known as the oldest public hospital in the United States of America. Although its historical beginnings date back to the 1600s, it was officially founded on the second floor of the New York City Almshouse in 1736, 40 years before the American Revolution. It has since been at the forefront of administering comprehensive patient care and medical education. Moreover, Bellevue has built a reputation for serving homeless, immigrant, or minority populations while also delivering care to United States presidents. This tradition of treating patients regardless of socioeconomic or racial status has made Bellevue one of the most historically renowned hospitals in the country. Today, Bellevue hospital represents a significant branch of the New York City health system and a public health leader. Moreover, it has housed pioneers in neurosurgery, including the father of functional ultrasonic neurosurgery, Dr. Russel Meyers, as well as Dr. Dorothy Klenke Nash, the only active female neurosurgeon in the United States from 1928 to 1960. Herein, we will explore Bellevue's historical and medical significance, from its humble beginnings to its current status as a public health leader.