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1.
bioRxiv ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39211079

ABSTRACT

Monocyte-derived macrophages recruited to injured tissues induce a maladaptive fibrotic response characterized by excessive production of collagen by local fibroblasts. Macrophages initiate this programming via paracrine factors, but it is unknown whether reciprocal responses from fibroblasts enhance profibrotic polarization of macrophages. We identify macrophage-fibroblast crosstalk necessary for injury-associated fibrosis, in which macrophages induced interleukin 6 ( IL-6 ) expression in fibroblasts via purinergic receptor P2rx4 signaling, and IL-6, in turn, induced arginase 1 ( Arg1 ) expression in macrophages. Arg1 contributed to fibrotic responses by metabolizing arginine to ornithine, which fibroblasts used as a substrate to synthesize proline, a uniquely abundant constituent of collagen. Imaging of idiopathic pulmonary fibrosis (IPF) lung samples confirmed expression of ARG1 in myeloid cells, and arginase inhibition suppressed collagen expression in cultured precision-cut IPF lung slices. Taken together, we define a circuit between macrophages and fibroblasts that facilitates cross-feeding metabolism necessary for injury-associated fibrosis.

2.
Article in English | MEDLINE | ID: mdl-39093622

ABSTRACT

ABSTRACT: Blunt cerebrovascular injuries are not as rare as they were once thought to be-but they still have the same potential for disastrous outcomes. They may occur following any trauma, but more common with higher energy transfer mechanisms. If stroke occurs, prompt recognition and treatment offers the best chance for optimal outcome. Early diagnosis and provision of antithrombotic therapy may prevent strokes, so screening of asymptomatic patients is recommended. Herein we will present what you need to know to diagnose and manage blunt cerebrovascular injury.

3.
Microcirculation ; : e12875, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38989907

ABSTRACT

OBJECTIVE: Tortuous microvessels are characteristic of microvascular remodeling associated with numerous physiological and pathological scenarios. Three-dimensional (3D) hemodynamics in tortuous microvessels influenced by red blood cells (RBCs), however, are largely unknown, and important questions remain. Is blood viscosity influenced by vessel tortuosity? How do RBC dynamics affect wall shear stress (WSS) patterns and the near-wall cell-free layer (CFL) over a range of conditions? The objective of this work was to parameterize hemodynamic characteristics unique to a tortuous microvessel. METHODS: RBC-resolved simulations were performed using an immersed boundary method-based 3D fluid dynamics solver. A representative tortuous microvessel was selected from a stimulated angiogenic network obtained from imaging of the rat mesentery and digitally reconstructed for the simulations. The representative microvessel was a venule with a diameter of approximately 20 µm. The model assumes a constant diameter along the vessel length and does not consider variations due to endothelial cell shapes or the endothelial surface layer. RESULTS: Microvessel tortuosity was observed to increase blood apparent viscosity compared to a straight tube by up to 26%. WSS spatial variations in high curvature regions reached 23.6 dyne/cm2 over the vessel cross-section. The magnitudes of WSS and CFL thickness variations due to tortuosity were strongly influenced by shear rate and negligibly influenced by tube hematocrit levels. CONCLUSIONS: New findings from this work reveal unique tortuosity-dependent hemodynamic characteristics over a range of conditions. The results provide new thought-provoking information to better understand the contribution of tortuous vessels in physiological and pathological processes and help improve reduced-order models.

4.
Minerva Surg ; 79(3): 273-285, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38847766

ABSTRACT

BACKGROUND: Colorectal (CRC) cancer is becoming a disease of the elderly. Ageing is the most significant risk factor for presenting CRC. Early diagnosis of CRC and management is the best way in achieving good outcomes and longer survival but patients aged ≥75 years are usually not screened for CRC. This group of patients is often required to be managed when they are symptomatic in the emergency setting with high morbidity and mortality rates. Our main aim is to provide clinical data about the management of elderly patients presenting complicated colorectal cancer who required emergency surgical management to improve their care. METHODS: The management of complicated COlorectal cancer in OLDER patients (CO-OLDER; ClinicalTrials.gov ID: NCT05788224; evaluated by the local ethical committee CPP EST III-France with the national number 2023-A01094-41) in the emergency setting project provides carrying out an observational multicenter international cohort study aimed to collect data about patients aged ≥75 years to assess modifiable risk factors for negative outcomes and mortality correlated to the emergency surgical management of this group of patients at risk admitted with a complicated (obstructed and perforated) CRC. The CO-OLDER protocol was approved by Institutional Review Board and released. Each CO-OLDER collaborator is asked to enroll ≥25 patients over a study period from 1st January 2018 to 30th October 2023. Data will be analyzed comparing two periods of study: before and after the COVID-19 pandemic. A sample size of 240 prospectively enrolled patients with obstructed colorectal cancer in a 5-month period was calculated. The secured database for entering anonymized data will be available for the period necessary to achieve the highest possible participation. RESULTS: One hundred eighty hospitals asked to be a CO-OLDER collaborator, with 36 potentially involved countries over the world. CONCLUSIONS: The CO-OLDER project aims to improve the management of elderly people presenting with a complicated colorectal cancer in the emergency setting. Our observational global study can provide valuable data on the effectiveness of different management strategies in improving primary assessment, management and outcomes for elderly patients with obstructed or perforated colorectal cancer in the emergency setting, guiding clinical decision-making. This information can help healthcare providers make informed decisions about the best course of action for these patients.


Subject(s)
COVID-19 , Colorectal Neoplasms , Humans , COVID-19/epidemiology , Aged , Aged, 80 and over , Male , Female , Risk Factors , Global Health , Intestinal Obstruction/surgery , Intestinal Obstruction/epidemiology
5.
bioRxiv ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38895236

ABSTRACT

Type 2 diabetes mellitus (T2DM) is associated with poor outcome after stroke. Peripheral monocytes play a critical role in the secondary injury and recovery of damaged brain tissue after stroke, but the underlying mechanisms are largely unclear. To investigate transcriptome changes and molecular networks across monocyte subsets in response to T2DM and stroke, we performed single-cell RNA-sequencing (scRNAseq) from peripheral blood mononuclear cells and bulk RNA-sequencing from blood monocytes from four groups of adult mice, consisting of T2DM model db/db and normoglycemic control db/+ mice with or without ischemic stroke. Via scRNAseq we found that T2DM expands the monocyte population at the expense of lymphocytes, which was validated by flow cytometry. Among the monocytes, T2DM also disproportionally increased the inflammatory subsets with Ly6C+ and negative MHC class II expression (MO.6C+II-). Conversely, monocytes from control mice without stroke are enriched with steady-state classical monocyte subset of MO.6C+II+ but with the least percentage of MO.6C+II- subtype. Apart from enhancing inflammation and coagulation, enrichment analysis from both scRNAseq and bulk RNAseq revealed that T2DM specifically suppressed type-1 and type-2 interferon signaling pathways crucial for antigen presentation and the induction of ischemia tolerance. Preconditioning by lipopolysaccharide conferred neuroprotection against ischemic brain injury in db/+ but not in db/db mice and coincided with a lesser induction of brain Interferon-regulatory-factor-3 in the brains of the latter mice. Our results suggest that the increased diversity and altered transcriptome in the monocytes of T2DM mice underlie the worse stroke outcome by exacerbating secondary injury and potentiating stroke-induced immunosuppression. Significance Statement: The mechanisms involved in the detrimental diabetic effect on stroke are largely unclear. We show here, for the first time, that peripheral monocytes have disproportionally altered the subsets and changed transcriptome under diabetes and/or stroke conditions. Moreover, genes in the IFN-related signaling pathways are suppressed in the diabetic monocytes, which underscores the immunosuppression and impaired ischemic tolerance under the T2DM condition. Our data raise a possibility that malfunctioned monocytes may systemically and focally affect the host, leading to the poor outcome of diabetes in the setting of stroke. The results yield important clues to molecular mechanisms involved in the detrimental diabetic effect on stroke outcome.

6.
Psychol Methods ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38869857

ABSTRACT

Propensity score analysis (PSA) is a prominent method to alleviate selection bias in observational studies, but missing data in covariates is prevalent and must be dealt with during propensity score estimation. Through Monte Carlo simulations, this study evaluates the use of imputation methods based on multiple random forests algorithms to handle missing data in covariates: multivariate imputation by chained equations-random forest (Caliber), proximity imputation (PI), and missForest. The results indicated that PI and missForest outperformed other methods with respect to bias of average treatment effect regardless of sample size and missing mechanisms. A demonstration of these five methods with PSA to evaluate the effect of participation in center-based care on children's reading ability is provided using data from the Early Childhood Longitudinal Study, Kindergarten Class of 2010-2011. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

7.
Mass Spectrom Rev ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940512

ABSTRACT

Dental caries, a prevalent global infectious condition affecting over 95% of adults, remains elusive in its precise etiology. Addressing the complex dynamics of caries demands a thorough exploration of taxonomic, potential, active, and encoded functions within the oral ecosystem. Metabolomic profiling emerges as a crucial tool, offering immediate insights into microecosystem physiology and linking directly to the phenotype. Identified metabolites, indicative of caries status, play a pivotal role in unraveling the metabolic processes underlying the disease. Despite challenges in metabolite variability, the use of metabolomics, particularly via mass spectrometry and nuclear magnetic resonance spectroscopy, holds promise in caries research. This review comprehensively examines metabolomics in caries prevention, diagnosis, and treatment, highlighting distinct metabolite expression patterns and their associations with disease-related bacterial communities. Pioneering in approach, it integrates singular and combinatory metabolomics methodologies, diverse biofluids, and study designs, critically evaluating prior limitations while offering expert insights for future investigations. By synthesizing existing knowledge, this review significantly advances our comprehension of caries, providing a foundation for improved prevention and treatment strategies.

8.
Nat Commun ; 15(1): 5483, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38942804

ABSTRACT

Dexamethasone is the standard of care for critically ill patients with COVID-19, but the mechanisms by which it decreases mortality and its immunological effects in this setting are not understood. Here we perform bulk and single-cell RNA sequencing of samples from the lower respiratory tract and blood, and assess plasma cytokine profiling to study the effects of dexamethasone on both systemic and pulmonary immune cell compartments. In blood samples, dexamethasone is associated with decreased expression of genes associated with T cell activation, including TNFSFR4 and IL21R. We also identify decreased expression of several immune pathways, including major histocompatibility complex-II signaling, selectin P ligand signaling, and T cell recruitment by intercellular adhesion molecule and integrin activation, suggesting these are potential mechanisms of the therapeutic benefit of steroids in COVID-19. We identify additional compartment- and cell- specific differences in the effect of dexamethasone that are reproducible in publicly available datasets, including steroid-resistant interferon pathway expression in the respiratory tract, which may be additional therapeutic targets. In summary, we demonstrate compartment-specific effects of dexamethasone in critically ill COVID-19 patients, providing mechanistic insights with potential therapeutic relevance. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients.


Subject(s)
COVID-19 Drug Treatment , COVID-19 , Cytokines , Dexamethasone , Lung , SARS-CoV-2 , Dexamethasone/therapeutic use , Dexamethasone/pharmacology , Humans , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/drug effects , Lung/drug effects , Lung/virology , Cytokines/metabolism , Cytokines/blood , Critical Illness , Male , Single-Cell Analysis , Female , Middle Aged , T-Lymphocytes/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , Aged , Lymphocyte Activation/drug effects
9.
J Periodontal Res ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38873831

ABSTRACT

AIM: The current study aimed to: (1) systematically review the published literature regarding the proteomics analyses of saliva and gingival crevicular fluid (GCF) in healthy humans and gingivitis and/or periodontitis patients; and (2) to identify the differentially expressed proteins (DEPs) based on the systematic review, and comprehensively conduct meta-analyses and bioinformatics analyses. METHODS: An online search of Web of Science, Scopus, and PubMed was performed without any restriction on the year and language of publication. After the identification of the DEPs reported by the included human primary studies, gene ontology (GO), the Kyoto encyclopedia of genes and genomes pathway (KEGG), protein-protein interaction (PPI), and meta-analyses were conducted. The risk of bias among the included studies was evaluated using the modified Newcastle-Ottawa quality assessment scale. RESULTS: The review identified significant differences in protein expression between healthy individuals and those with gingivitis and periodontitis. In GCF, 247 proteins were upregulated and 128 downregulated in periodontal diseases. Saliva analysis revealed 79 upregulated and 70 downregulated proteins. There were distinct protein profiles between gingivitis and periodontitis, with 159 and 31 unique upregulated proteins in GCF, respectively. Meta-analyses confirmed significant upregulation of various proteins in periodontitis, including ALB and MMP9, while CSTB and GSTP1 were downregulated. AMY1A and SERPINA1 were upregulated in periodontitis saliva. HBD was upregulated in gingivitis GCF, while DEFA3 was downregulated. PPI analysis revealed complex networks of interactions among DEPs. GO and KEGG pathway analyses provided insights into biological processes and pathways associated with periodontal diseases. CONCLUSION: The ongoing MS-based proteomics studies emphasize the need for a highly sensitive and specific diagnostic tool for periodontal diseases. Clinician acceptance of the eventual diagnostic method relies on its ability to provide superior or complementary information to current clinical assessment procedures. Future research should prioritize the multiplex measurement of multiple biomarkers simultaneously to enhance diagnostic accuracy and large study cohorts are necessary to ensure the validity and reliability of research findings.

10.
Knee Surg Sports Traumatol Arthrosc ; 32(9): 2290-2296, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38738862

ABSTRACT

PURPOSE: The purpose of this study was to examine the effects of intraoperative technology use on the rate of using polyethylene liners 15 mm or greater during primary total knee arthroplasty (TKA). METHODS: There were 103,295 implants from 16,386 primary unilateral TKAs performed on 14,253 patients at a single institution between 1 January 2018, and 30 June 2022, included in the current study. Robotic assistance and navigation guidance were used in 1274 (8%) and 8345 (51%) procedures, respectively. The remaining 6767 TKAs (41%) were performed manually. Polyethylene liners were manually identified and further subcategorised by implant thickness. Patients who underwent robotic-assisted TKA were younger (p < 0.001) and more likely to be male (p < 0.001) compared to patients who underwent navigation-guided or manual TKAs. RESULTS: Average polyethylene liner thickness was similar between groups (10.5 ± 1.5 mm for robotic-assisted TKAs, 10.9 ± 1.8 mm for navigation-guided TKAs and 10.8 ± 1.8 mm for manual TKAs). The proportions of polyethylene liners 15 mm or greater used were 4.9%, 3.8% and 1.9% for navigation-guided, manual and robotic-assisted procedures, respectively (p < 0.001). Multivariate regression analyses demonstrated that navigation-guided (odds ratio [OR]: 2.6, 95% confidence Interval [CI]: [1.75-4.07], p < 0.001) and manual (OR: 2.0, 95% CI: [1.34-3.20], p = 0.001) procedures were associated with an increased use of polyethylene liners 15 mm or greater. CONCLUSION: Robotic-assisted TKA was associated with a lower proportion of polyethylene liners 15 mm or greater used compared to navigation-guided and manual TKA. These findings suggest that robotic assistance can reduce human error via a more precise cutting system, limit over-resection of the tibia and flexion-extension gap mismatch and ultimately allow for more appropriately sized implants. LEVEL OF EVIDENCE: Level III, retrospective cohort study.


Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Polyethylene , Robotic Surgical Procedures , Surgery, Computer-Assisted , Humans , Arthroplasty, Replacement, Knee/methods , Arthroplasty, Replacement, Knee/instrumentation , Male , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/instrumentation , Aged , Female , Middle Aged , Surgery, Computer-Assisted/methods , Surgery, Computer-Assisted/instrumentation , Retrospective Studies , Prosthesis Design
11.
Am Surg ; 90(6): 1161-1166, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38751046

ABSTRACT

BACKGROUND: Blunt traumatic abdominal wall hernias (TAWHs) are rare but require a variety of operative techniques to repair including bone anchor fixation (BAF) when tissue tears off bony structures. This study aimed to provide a descriptive analysis of BAF technique for blunt TAWH repair. Bone anchor fixation and no BAF repairs were compared, hypothesizing increased hernia recurrence with BAF repair. METHODS: A secondary analysis of the WTA blunt TAWH multicenter study was performed including all patients who underwent repair of their TAWH. Patients with BAF were compared to those with no BAF with bivariate analyses. RESULTS: 176 patients underwent repair of their TAWH with 41 (23.3%) undergoing BAF. 26 (63.4%) patients had tissue fixed to bone, with 7 of those reinforced with mesh. The remaining 15 (36.6%) patients had bridging mesh anchored to bone. The BAF group had a similar age, sex, body mass index, and injury severity score compared to the no BAF group. The time to repair (1 vs 1 days, P = .158), rate of hernia recurrence (9.8% vs 12.7%, P = .786), and surgical site infection (SSI) (12.5% vs 15.6%, P = .823) were all similar between cohorts. CONCLUSIONS: This largest series to date found nearly one-quarter of TAWH repairs required BAF. Bone anchor fixation repairs had a similar rate of hernia recurrence and SSI compared to no BAF repairs, suggesting this is a reasonable option for repair of TAWH. However, future prospective studies are needed to compare specific BAF techniques and evaluate long-term outcomes including patient-centered outcomes such as pain and quality of life.


Subject(s)
Herniorrhaphy , Surgical Mesh , Wounds, Nonpenetrating , Humans , Male , Female , Wounds, Nonpenetrating/surgery , Herniorrhaphy/methods , Adult , Middle Aged , Abdominal Injuries/surgery , Suture Anchors , Recurrence , Retrospective Studies , Treatment Outcome , Hernia, Ventral/surgery , Hernia, Abdominal/surgery , Hernia, Abdominal/etiology , Injury Severity Score , Surgical Wound Infection/etiology , Surgical Wound Infection/epidemiology
12.
Arch Dermatol Res ; 316(5): 146, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38696005

ABSTRACT

Secondary malignancies are rare but devastating complications of longstanding burn scars. Squamous cell carcinoma is the most common, followed by basal cell carcinoma and melanomas. There are fewer than 50 total reported cases of malignant melanomas arising in burn scars. We report a case of malignant melanoma arising within a longstanding burn scar confirmed by histology, FISH, and PRAME staining to further characterize melanomas arising in burn scars and to illustrate the diagnostic challenges they present.


Subject(s)
Burns , Cicatrix , Melanoma , Skin Neoplasms , Female , Humans , Male , Middle Aged , Burns/complications , Burns/diagnosis , Burns/pathology , Cicatrix/etiology , Cicatrix/pathology , Cicatrix/diagnosis , gp100 Melanoma Antigen , In Situ Hybridization, Fluorescence , Melanoma/diagnosis , Melanoma/pathology , Melanoma/complications , Melanoma, Cutaneous Malignant , Skin Neoplasms/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/etiology
13.
bioRxiv ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38746396

ABSTRACT

Cancer-associated mutations have been documented in normal tissues, but the prevalence and nature of somatic copy number alterations and their role in tumor initiation and evolution is not well understood. Here, using single cell DNA sequencing, we describe the landscape of CNAs in >42,000 breast epithelial cells from women with normal or high risk of developing breast cancer. Accumulation of individual cells with one or two of a specific subset of CNAs (e.g. 1q gain and 16q, 22q, 7q, and 10q loss) is detectable in almost all breast tissues and, in those from BRCA1 or BRCA2 mutations carriers, occurs prior to loss of heterozygosity (LOH) of the wildtype alleles. These CNAs, which are among the most common associated with ductal carcinoma in situ (DCIS) and malignant breast tumors, are enriched almost exclusively in luminal cells not basal myoepithelial cells. Allele-specific analysis of the enriched CNAs reveals that each allele was independently altered, demonstrating convergent evolution of these CNAs in an individual breast. Tissues from BRCA1 or BRCA2 mutation carriers contain a small percentage of cells with extreme aneuploidy, featuring loss of TP53 , LOH of BRCA1 or BRCA2 , and multiple breast cancer-associated CNAs in addition to one or more of the common CNAs in 1q, 10q or 16q. Notably, cells with intermediate levels of CNAs are not detected, arguing against a stepwise gradual accumulation of CNAs. Overall, our findings demonstrate that chromosomal alterations in normal breast epithelium partially mirror those of established cancer genomes and are chromosome- and cell lineage-specific.

14.
bioRxiv ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38798460

ABSTRACT

T cells have emerged as sex-dependent orchestrators of pain chronification but the sexually dimorphic mechanisms by which T cells control pain sensitivity is not resolved. Here, we demonstrate an influence of regulatory T cells (Tregs) on pain processing that is distinct from their canonical functions of immune regulation and tissue repair. Specifically, meningeal Tregs (mTregs) express the endogenous opioid, enkephalin, and mTreg-derived enkephalin exerts an antinociceptive action through a presynaptic opioid receptor signaling mechanism that is dispensable for immunosuppression. mTregs are both necessary and sufficient for suppressing mechanical pain sensitivity in female but not male mice. Notably, the mTreg modulation of pain thresholds depends on sex-hormones and expansion of enkephalinergic mTregs during gestation imparts a remarkable pregnancy-induced analgesia in a pre-existing, chronic, unremitting neuropathic pain model. These results uncover a fundamental sex-specific, pregnancy-pronounced, and immunologically-derived endogenous opioid circuit for nociceptive regulation with critical implications for pain biology and maternal health.

15.
J Clin Invest ; 134(9)2024 May 01.
Article in English | MEDLINE | ID: mdl-38690733

ABSTRACT

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.RESULTSIncreasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, formation of neutrophil extracellular traps, and T cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma Igs and B cells and dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to failure of viral clearance in patients with fatal illness.CONCLUSIONOur longitudinal multiomics profiling study revealed temporal coordination across diverse omics that potentially explain the disease progression, providing insights that can inform the targeted development of therapies for patients hospitalized with COVID-19, especially those who are critically ill.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, and R01AI122220); and National Science Foundation (DMS2310836).


Subject(s)
COVID-19 , Severity of Illness Index , Adult , Aged , Female , Humans , Male , Middle Aged , COVID-19/immunology , COVID-19/mortality , COVID-19/blood , Cytokines/blood , Cytokines/immunology , Longitudinal Studies , Multiomics
16.
Prev Med ; 185: 108010, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38801836

ABSTRACT

BACKGROUND: Limited research exists on contemporary opioid overdose mortality burden and trends in New York State, with most studies focusing on New York City. This study aimed to assess opioid overdose burden and death trends in New York State by age, sex, race/ethnicity, geographic area, opioid type, and overdose intent from 1999 to 2020. METHODS: Mortality data were obtained from the Centers for Disease Control and Prevention's WONDER database. Opioid overdose decedents were identified using relevant International Classification of Diseases, 10th Revision codes. Joinpoint regression analyzed trends, estimating annual and average annual percentage changes in age-adjusted mortality rates (AAMR). 95% confidence intervals were derived using the Parametric Method. RESULTS: From 1999 to 2020, New York State recorded 34,109 opioid overdose deaths (AAMR = 7.9 per 100,000 persons; 95% CI: 7.8-7.9). The overall trend increased by 12.6% per year (95% CI: 10.8, 14.4) from 2004 to 2020. Subgroups exhibited varying trends, with an 11.1% yearly increase among Non-Hispanic White persons from 2007 to 2020 (95% CI: 9.0, 13.2), a 24.6% annual rise among Non-Hispanic Black persons from 2012 to 2020 (95% CI: 17.7, 31.8), and an 18.3% increase yearly among Hispanic individuals from 2011 to 2020 (95% CI: 14.0, 22.9). Recent trends have worsened in both males and females, across all age groups, in both New York City (NYC) and areas outside NYC, and for heroin, natural and semisynthetic opioids, and synthetic opioids. CONCLUSIONS: Opioid overdose mortality in New York State has worsened significantly in the last two decades. Further research is essential to identify driving factors for targeted public health interventions.


Subject(s)
Opiate Overdose , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Analgesics, Opioid/poisoning , Drug Overdose/mortality , New York/epidemiology , Opiate Overdose/mortality , Opiate Overdose/epidemiology , Opioid-Related Disorders/mortality , White , Black or African American , Hispanic or Latino
17.
Ann Biomed Eng ; 52(9): 2457-2472, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38796670

ABSTRACT

Biomimetic tumor microenvironment models bridge the gap between in vitro and in vivo systems and serve as a useful way to address the modeling challenge of how to recreate the cell and system complexity associated with real tissues. Our laboratory has developed an ex vivo rat mesentery culture model, which allows for simultaneous investigation of blood and lymphatic microvascular network remodeling in an intact tissue environment. Given that angiogenesis and lymphangiogenesis are key contributors to the progression of cancer, the objective of this study was to combine tissue and tumor spheroid culture methods to establish a novel ex vivo tumor spheroid-tissue model by verifying its use for evaluating the effects of cancer cell behavior on the local microvascular environment. H1299 or A549 tumor spheroids were formed via hanging drop culture and seeded onto rat mesenteric tissues harvested from adult male Wistar rats. Tissues with transplanted spheroids were cultured in serum-free media for 3 to 5 days. PECAM, NG2, CD11b, and αSMA labeling identified endothelial cells, pericytes, immune cells, and smooth muscle cells, respectively. Time-lapse imaging confirmed cancer cell type specific migration. In addition to increasing PECAM positive capillary sprouting and LYVE-1 positive endothelial cell extensions indicative of lymphangiogenesis, tumor spheroid presence induced the formation of lymphatic/blood vessel connections and the formation of hybrid, mosaic vessels that were characterized by discontinuous LYVE-1 labeling. The results support the application of a novel tumor spheroid microenvironment model for investigating cancer cell-microvascular interactions.


Subject(s)
Lymphatic Vessels , Rats, Wistar , Spheroids, Cellular , Tumor Microenvironment , Animals , Spheroids, Cellular/pathology , Humans , Male , Rats , Lymphatic Vessels/pathology , Lymphatic Vessels/physiopathology , Lymphangiogenesis , Cell Line, Tumor , Neovascularization, Pathologic/pathology , Vascular Remodeling , Microvessels/pathology , A549 Cells
18.
Article in English | MEDLINE | ID: mdl-38695887

ABSTRACT

AIM: This study aimed to evaluate the impact of the WSES-AAST guidelines in clinical practice and to investigate the knowledge, attitudes, and practices of emergency surgeons in managing the complications of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: The MIBODI survey is a cross-sectional study among WSES members designed as an international web-based survey, according to the Checklist for Reporting Results of Internet E-Surveys, to collect data on emergency surgeons' knowledge, attitudes, and practices concerning the management of patients presenting with acute complications of CD and UC. The questionnaire was composed of 30 questions divided into five sections: (1) demographic data, (2) primary evaluation, (3) non-operative management, (4) operative management, and (5) perianal sepsis management. RESULTS: Two hundred and forty-two surgeons from 48 countries agreed to participate in the survey. The response rate was 24.2% (242/1000 members on WSES mail list). Emergency surgeons showed high adherence to recommendations for 6 of the 21 assessed items, with a "correct" response rate greater than or equal to 60%, according to WSES-AAST recommendations. Nine critical issues were highlighted, with correct answers at a rate of less than 50%. CONCLUSIONS: Inflammatory bowel disease is a complex disease that requires a multidisciplinary approach with close collaboration between gastroenterologists and surgeons. Emergency surgeons play a crucial role in managing complications related to IBD. One year after publication, the MIBODI study showed significant global implementation of the WSES-AAST guidelines in clinical practice, offering an imperative tool in the improved management of IBD in emergency and urgent settings.

19.
GMS Infect Dis ; 12: Doc01, 2024.
Article in English | MEDLINE | ID: mdl-38764941

ABSTRACT

Uncomplicated cystitis is affecting many women of all ages and has a great impact on the quality of life, especially in women suffering from recurrent, uncomplicated cystitis. By far the most frequent uropathogen, E. coli, may have acquired increasing resistance against a variety of oral antibiotics, which may differ between countries and regions. Therefore, local resistance data are important to be considered. On the other hand, non-antibiotic therapy has also become an option which should be discussed and offered to the patient. In patients suffering from recurrent uncomplicated cystitis, individual risk factors and possible behavioral changes should first be taken into account. Non-antimicrobial prophylactic strategies shown to be successful in well-designed clinical studies are the next options. Long term antibiotic prophylaxis, however, should only be considered as a last option. For some of those patients self-diagnosis and self-treatment may be suitable, e.g. by using a recognized questionnaire.

20.
Am Surg ; : 31348241256084, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775262

ABSTRACT

BACKGROUND: The abdominal seat belt sign (SBS) is associated with an increased risk of hollow viscus injury (HVI). Older age is associated with worse outcomes in trauma patients. Thus, older trauma patients ≥65 years of age (OTPs) may be at an increased risk of HVI with abdominal SBS. Therefore, we hypothesized an increased incidence of HVI and mortality for OTPs vs younger trauma patients (YTPs) with abdominal SBS. STUDY DESIGN: This post hoc analysis of a multi-institutional, prospective, observational study (8/2020-10/2021) included patients >18 years old with an abdominal SBS who underwent abdominal computed tomography (CT) imaging. Older trauma patients were compared to YTPs (18-64 years old) with bivariate analyses. RESULTS: Of the 754 patients included in this study from nine level-1 trauma centers, there were 110 (14.6%) OTPs and 644 (85.4%) YTPs. Older trauma patients were older (mean 75.3 vs 35.8 years old, P < .01) and had a higher mean Injury Severity Score (10.8 vs 9.0, P = .02). However, YTPs had an increased abdominal abbreviated-injury scale score (2.01 vs 1.63, P = .02). On CT imaging, OTPs less commonly had intraabdominal free fluid (21.7% vs 11.9%, P = .02) despite a similar rate of abdominal soft tissue contusion (P > .05). Older trauma patients also had a statistically similar rate of HVI vs YTPs (5.5% vs 9.8%, P = .15). Despite this, OTPs had increased mortality (5.5% vs 1.1%, P < .01) and length of stay (LOS) (5.9 vs 4.9 days P < .01). CONCLUSION: Despite a similar rate of HVI, OTPs with an abdominal SBS had an increased rate of mortality and LOS. This suggests the need for heightened vigilance when caring for OTPs with abdominal SBS.

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