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1.
Bioact Mater ; 40: 64-73, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38948254

ABSTRACT

Composite biomaterials comprising polylactide (PLA) and hydroxyapatite (HA) are applied in bone, cartilage and dental regenerative medicine, where HA confers osteoconductive properties. However, after surgical implantation, adverse immune responses to these composites can occur, which have been attributed to size and morphology of HA particles. Approaches to effectively modulate these adverse immune responses have not been described. PLA degradation products have been shown to alter immune cell metabolism (immunometabolism), which drives the inflammatory response. Accordingly, to modulate the inflammatory response to composite biomaterials, inhibitors were incorporated into composites comprised of amorphous PLA (aPLA) and HA (aPLA + HA) to regulate glycolytic flux. Inhibition at specific steps in glycolysis reduced proinflammatory (CD86+CD206-) and increased pro-regenerative (CD206+) immune cell populations around implanted aPLA + HA. Notably, neutrophil and dendritic cell (DC) numbers along with proinflammatory monocyte and macrophage populations were decreased, and Arginase 1 expression among DCs was increased. Targeting immunometabolism to control the proinflammatory response to biomaterial composites, thereby creating a pro-regenerative microenvironment, is a significant advance in tissue engineering where immunomodulation enhances osseointegration and angiogenesis, which could lead to improved bone regeneration.

3.
Blood Adv ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38916866

ABSTRACT

We aim to evaluate impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using CIBMTR registry data for HCTs done between 2013 and 2019. In all 1597 undergoing HCT for myelofibrosis, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study eligible, 1032 patients who received peripheral blood grafts for chronic phase myelofibrosis, 38% recipients of haploidentical-HCT were of non-White/Caucasian ethnicity. Matched sibling donor (MSD)-HCTs were independently associated with superior overall survival (OS) in the first 3 months [reference MSD, haploidentical HR 5.80 (95% CI 2.52-13.35), matched unrelated HR 4.50 (95% CI 2.24-9.03), and mismatched unrelated HR 5.13 (95% CI 1.44-18.31), P<0.001]. This difference in OS aligns with lower graft failure with MSD [haploidentical HR 6.11 (95%CI 2.98-12.54), matched unrelated HR 2.33 (95%CI 1.20-4.51), mismatched unrelated HR 1.82 (95%CI 0.58-5.72). There was no significant difference in OS among haploidentical, matched unrelated, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months post-HCT, relapse, disease-free survival or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. While MSDs remain a superior donor option due to improved engraftment, there is no significant difference in HCT outcomes from haploidentical and matched unrelated donors. These results establish haploidentical-HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.

4.
Article in English | MEDLINE | ID: mdl-38787893

ABSTRACT

INTRODUCTION: Pedicle subtraction osteotomy (PSO) is a complex surgical procedure that provides correction of moderate sagittal imbalance. Surgical complications have adverse effects on patient outcomes and healthcare costs, making it imperative for clinical researchers to focus on minimizing complications. However, when it comes to risk modeling of PSO surgery, there is currently no consensus on which patient characteristics or measures should be used. This study aimed to describe complications and compare the performance of various sociodemographic characteristics, surgical variables, and established risk indices in predicting postoperative complications, infections, and readmissions after lumbar PSO surgeries. METHODS: A review was conducted on 191 patients who underwent PSO surgery at a single institution by a single fellowship-trained orthopaedic spine surgeon between January 1, 2018, and December 31, 2021. Demographic, intraoperative, and postoperative data within 30 days, 1 year, and 2 years of the index procedure were evaluated. Descriptive statistics, t-test, chi-squared analysis, and logistic regression models were used. RESULTS: Intraoperative complications were significantly associated with coronary artery disease (odds ratios [OR] 3.95, P = 0.03) and operating room time (OR 1.01, P = 0.006). 30-day complications were significantly cardiovascular disease (OR 2.68, P = 0.04) and levels fused (OR 1.10, P = 0.04). 2-year complications were significantly associated with cardiovascular disease (OR 2.85, P = 0.02). 30-day readmissions were significantly associated with sex (4.47, 0.04) and length of hospital stay (χ2 = 0.07, P = 0.04). 2-year readmissions were significantly associated with age (χ2 = 0.50, P = 0.03), hypertension (χ2 = 4.64, P = 0.03), revision surgeries (χ2 = 5.46, P = 0.02), and length of hospital stay (χ2 = 0.07, P = 0.03). DISCUSSION: This study found that patients with coronary vascular disease and longer fusions were at higher risk of postoperative complications and patients with notable intraoperative blood loss were at higher risk of postoperative infections. In addition, physicians should closely follow patients with extended postoperative hospital stays, with advanced age, and undergoing revision surgery because these patients were more likely to be readmitted to the hospital.

5.
Leukemia ; 38(7): 1564-1569, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38750138

ABSTRACT

CD19 CAR T-cell (CAR-T) therapy is commonly administered to patients with relapsed or refractory large B-cell lymphomas (LBCL), but salvage or bridging therapy can sometimes lead to a complete response (CR) prior to infusion. Limited studies have assessed the outcomes of patients infused in CR. A total of 134 patients with LBCL in CR prior to CAR-T infusion were identified from the CIBMTR registry, with median prior lines of therapy of 3 (range 2-9). At two years post-infusion, the probability of progression-free survival was 43.5% (95% CI 34.4-52.8) and the probability of overall survival was 63.8% (95% CI 54.4-72.6). The cumulative incidence rates of non-relapse mortality and relapse/progression at two years were 9.2% (95% CI 4.5-15.4) and 47.3% (95% CI 38.2-56.6), respectively. The rate of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were 2.2% and 8.2%, respectively. In summary, CAR-T in heavily pretreated patients with LBCL who are in CR following two or more lines of prior therapy demonstrate that a subset of patients may remain free of progression at two years. Additionally, the toxicity profile was impressive with very low rates of grade 3 CRS and ICANS.


Subject(s)
Immunotherapy, Adoptive , Lymphoma, Large B-Cell, Diffuse , Remission Induction , Humans , Male , Middle Aged , Female , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Adult , Aged , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/immunology , Young Adult , Receptors, Chimeric Antigen/immunology , Survival Rate , Follow-Up Studies , Antigens, CD19/immunology , Pathologic Complete Response
6.
Angew Chem Int Ed Engl ; 63(25): e202405779, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38619535

ABSTRACT

Herein, we describe a general hydrodefunctionalization protocol of alcohols and amines through a common isonitrile intermediate. To cleave the relatively inert C-NC bond, we leveraged dual hydrogen atom transfer (HAT) and photoredox catalysis to generate a nucleophilic boryl radical, which readily forms an imidoyl radical intermediate from the isonitrile. Rapid ß-scission then accomplishes defunctionalization. This method has been applied to the hydrodefunctionalization of both amine and alcohol-containing pharmaceuticals, natural products, and biomolecules. We extended this approach to the reduction of carbonyls and olefins to their saturated counterparts, as well as the hydrodecyanation of alkyl nitriles. Both experimental and computational studies demonstrate a facile ß-scission of the imidoyl radical, and reconcile differences in reactivity between nitriles and isonitriles within our protocol.

7.
Res Sq ; 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38464040

ABSTRACT

Skin fibrosis is a clinical problem with devastating impacts but limited treatment options. In the setting of diabetes, insulin administration often causes local dermal fibrosis, leading to a range of clinical sequelae including impeded insulin absorption. Mechanical forces are important drivers of fibrosis and, clinically, physical tension offloading at the skin level using an elastomeric patch significantly reduces wound scarring. However, it is not known whether tension offloading could similarly prevent skin fibrosis in the setting of pro-fibrotic injections. Here, we develop a porcine model using repeated local injections of bleomycin to recapitulate key features of insulin-induced skin fibrosis. Using histologic, tissue ultrastructural, and biomechanical analyses, we show that application of a tension-offloading patch both prevents and rescues existing skin fibrosis from bleomycin injections. By applying single-cell transcriptomic analysis, we find that the fibrotic response to bleomycin involves shifts in myeloid cell dynamics from favoring putatively pro-regenerative to pro-fibrotic myeloid subtypes; in a mechanomodulatory in vitro platform, we show that these shifts are mechanically driven and reversed by exogenous IL4. Finally, using a human foreskin xenograft model, we show that IL4 treatment mitigates bleomycin-induced dermal fibrosis. Overall, this study highlights that skin tension offloading, using an FDA cleared, commercially available patch, could have significant potential clinical benefit for the millions of patients dependent on insulin.

8.
Global Spine J ; : 21925682241242693, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38532704

ABSTRACT

STUDY DESIGN: Systematic review. OBJECTIVES: Intraoperative neuromonitoring (IOMN) has become a standard practice in the detection and prevention of nerve damage and postoperative deficit. While multicenter studies have addressed this inquiry, there have been no systematic reviews to date. This systematic review identifies the leading causes of IONM alerts during adult spinal deformity (ASD) surgeries. METHODS: Following PRISMA guidelines, a literature search was performed in PubMed and Embase. IONM alert causes were grouped by equivalent terms used across different studies and binned into larger categories, including surgical maneuver, Changes in blood pressure/temperature, Oxygenation, Anesthesia, Patient position, and Unknown. RESULTS: Inclusion criteria were studies on adult patients receiving ASD correction surgery using IONM with documented alert causes. 1544 references were included in abstract review, 128 in full text review, and 16 studies qualified for data extraction. From those studies, there was a total of 3945 adult patients with 299 IONM alerts. Surgical maneuver led the alert causes (258 alerts/86.3%), with signal loss most commonly occurring at correction or osteotomy (101/33.8% and 95/31.8% respectively). Pedicle screw placement caused 35 alerts (11.7%). Changes in temperature and blood pressure were the third largest category (34/11.4%). CONCLUSIONS: The most frequent causes of IONM alerts in ASD surgery were surgical maneuvers such as correction, osteotomy, and pedicle screw placement. This information provides spine surgeons with a quantitative perspective on the causes of IONM changes and show that most occur at predictable times during ASD surgery.

9.
Global Spine J ; : 21925682241226821, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38197607

ABSTRACT

STUDY DESIGN: Retrospective Cohort Analysis. OBJECTIVES: Extended hospital length of stay (LOS) poses a significant cost burden to patients undergoing adult spinal deformity (ASD) surgery. The purpose of this study is to investigate the relationship between late-week surgery and LOS in patients undergoing ASD surgery. METHODS: 256 patients who underwent ASD surgery between January 2018 and December 2021 by a single fellowship-trained orthopedic spine surgeon comprised the patient sample. Demographics, intraoperative, and perioperative data were collected for the 256 patients who underwent ASD surgery. Patients were divided into two groups based on surgical day of the week: (1) Early-week (Monday/Tuesday) n = 126 and (2) Late-week (Thursday/Friday) n = 130. Descriptive statistics, T-tests, and linear and logistic regression models were used to analyze the data. RESULTS: Surgical details and sociodemographic characteristics did not differ between the groups. When controlling for TLIF/DLIF status and PSO status there was no difference in mean length of stay between the groups. The late-week group was associated with a greater risk of 30-day readmission, but there was no difference in complications, infections, or intraoperative complications. CONCLUSIONS: We found no difference in mean length of stay between surgeries performed early in the week vs late in the week. Although late-week surgeries had higher 30-day readmission risk, all other outcomes, including complication rates, showed no significant differences. When adequate weekend post-operative care is available, we do not advise restricting ASD surgeries to specific weekdays.

10.
J Am Acad Orthop Surg ; 32(1): e33-e43, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37467386

ABSTRACT

INTRODUCTION: Pedicle subtraction osteotomies (PSOs) are complex spinal deformity surgeries that are associated with high complication rates. They are typically done by an experienced spine surgeon with another attending, resident, or physician assistant serving as the first assistant. The purpose of this study was to determine whether selecting a surgical team for single-level PSO based on case difficulty and fusion length could equalize intraoperative and perioperative outcomes among three groups: dual-attending (DA), attending and orthopaedic resident (RS), and attending and physician assistant (PA). METHODS: This study was a retrospective cohort analysis of 312 patients undergoing single-level thoracic or lumbar PSO from January 2007 to December 2020 by a fellowship-trained orthopaedic spine surgeon. Demographic, intraoperative, and perioperative data within 30 days and 2 years of the index procedure were analyzed. RESULTS: Patient demographics did not markedly differ between surgical groups. The mean cohort age was 64.5 years with BMI 31.9 kg/m 2 . Patients with the DA approach had a significantly longer surgical time (DA = 412 min vs. resident = 372 min vs. physician assistant = 323 min; P < 0.001). Patients within the DA group experienced a significantly lower rate of infection (DA = 2.1% [3/140] vs. RS = 7.9% [9/114] vs. PA = 1.7% [1/58], P = 0.043), surgical complication rate (DA = 26% [37/140] vs. RS = 41% [47/114] vs. PA = 33% [19/58], P < 0 .001), and readmission rate (DA = 6.4% [9/140] vs. RS = 12.3% [14/114] vs. PA = 19% [11/58] P = 0.030) within 30 days of surgery. No notable differences were observed among groups in 2-year complication, infection, readmission, or revision surgery rates. CONCLUSIONS: These study results support the DA surgeon approach. Resident involvement, even in less complex cases, can still negatively affect perioperative outcomes. Additional selection criteria development is needed.


Subject(s)
Osteotomy , Spinal Fusion , Humans , Middle Aged , Retrospective Studies , Osteotomy/adverse effects , Osteotomy/methods , Spine , Cohort Studies , Spinal Fusion/methods , Treatment Outcome
11.
Clin Spine Surg ; 37(3): E152-E157, 2024 04 01.
Article in English | MEDLINE | ID: mdl-38158604

ABSTRACT

STUDY DESIGN: A single-institution, retrospective cohort study. OBJECTIVE: The objective was to present demographic characteristics, mechanism of injuries, lengths of stay, intensive care unit (ICU) days, discharge locations, and causes of 90-day readmission for patients with subaxial spinal cord injuries resulting in paraplegia or tetraplegia. SUMMARY OF BACKGROUND DATA: Spinal cord injuries resulting in paraplegia or tetraplegia are rare injuries with debilitating outcomes. Numerous advances have occurred in caring for these patients, but patients still experience multiple complications. The severity of these injuries and numerous complications result in prolonged hospital stays and the need for extensive rehabilitation. METHODS: Twelve patients with subaxial spinal cord injury resulting in paraplegia or tetraplegia from a level 1 adult trauma center were reviewed. The primary outcomes included hospital length of stay, ICU days, intrahospital complications, 90-day readmission rates, and discharge location. We reviewed the literature for these outcomes in spinal cord injuries. RESULTS: For patients with subaxial spinal cord injuries resulting in paraplegia and tetraplegia, the average age was 36.0 years, and most were male [91.7% (11/12)]. The most common mechanism of injury was gunshot wounds[41.7% (5/12)]. Patients spent an average of 46.3 days in the hospital and 30.7 days in the ICU. Respiratory complications were the most common (9 patients). Fifty percent of patients (6/12) were discharged to the inpatient spinal cord rehab center, and 16.7% (2/12) expired while in the hospital. Two patients (20.0%) were readmitted within 90 days of discharge. CONCLUSIONS: Most patients with subaxial spinal cord injuries resulting in paraplegia or tetraplegia were young males with high-energy traumas. Many patients had intrahospital complications, and most were discharged to the hospital spinal rehab center. These findings likely stem from the severity of paraplegia and tetraplegia injuries and the need for rehabilitation.


Subject(s)
Spinal Cord Injuries , Wounds, Gunshot , Adult , Female , Humans , Male , Paraplegia/complications , Paraplegia/rehabilitation , Quadriplegia/complications , Retrospective Studies , Spinal Cord Injuries/complications , Spinal Cord Injuries/rehabilitation , Wounds, Gunshot/complications
12.
Trop Med Infect Dis ; 8(12)2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38133447

ABSTRACT

Chagas disease is a public health problem in the Americas, from the southern United States (USA) to Argentina. In the USA, less than 1% of domestic cases have been identified and less than 0.3% of total cases have received treatment. Little is known about affected immigrant Latin American communities. A prospective study was conducted to assess knowledge about Chagas disease among the Latin American community living in the Greater New Orleans area. Participants answered a baseline questionnaire, viewed a short educational video presentation, completed a post-presentation questionnaire, and were screened with an FDA-approved blood rapid diagnostic test (RDT). A total of 154 participants from 18 Latin American countries (n = 138) and the USA (n = 16) were enrolled and screened for Trypanosoma cruzi infection. At baseline, 57% of the participants knew that Chagas disease is transmitted through an insect vector, and 26% recognized images of the vector. Following the administration of an educational intervention, the participants' knowledge regarding vector transmission increased to 91% and 35% of participants were able to successfully identify images of the vector. Five participants screened positive for T. cruzi infection, indicating a 3.24% [95%CI: 1.1-7.5%] prevalence of Trypanosoma cruzi infection within the Latin American community of the New Orleans area. Results highlight the urgent need for improving access to education and diagnostics of Chagas disease.

13.
Article in English | MEDLINE | ID: mdl-37967074

ABSTRACT

INTRODUCTION: With the increasing use of the internet for health information, it is essential to prioritize resources that match the reading level of patients and parents. Limited health literacy is a notable issue in the United States, creating a financial burden and negatively affecting patient outcomes. This study aimed to assess the availability and readability of pediatric hospital web pages concerning two prevalent spine conditions in children, spondylolisthesis and spondylolysis, specifically examining whether the available resources meet the recommended sixth grade reading level. METHODS: A total of 179 pediatric hospital web pages were assessed for their availability and readability of spondylolisthesis and spondylolysis patient information. The web pages' readability was assessed using five readability formulae. Descriptive statistics and Student t-tests were performed on the collected scores with significance set at P < 0.05. RESULTS: Among the analyzed hospitals, 40.2% had no information on spondylolisthesis or spondylolysis, 20.1% mentioned treating these conditions, 7.8% had < 100 dedicated words, and only 31.8% had dedicated web pages with more than 100 words on these conditions. The average reading grade level for the evaluated web pages was 12.0, indicating a high school education level is required for comprehension. None of the web pages were written below the recommended sixth grade reading level. DISCUSSION: The readability of the limited resources was markedly higher than the recommended reading level. In addition, this study emphasizes the need for enhanced accessibility and readability of online patient information from pediatric hospitals to improve parental comprehension and informed decision-making. Physicians should consider identifying online resources that they consider of high quality and acceptable readability to support better patient understanding and outcomes.


Subject(s)
Health Literacy , Spondylolisthesis , Child , Humans , United States , Comprehension , Hospitals, Pediatric
14.
Nat Commun ; 14(1): 7774, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38012131

ABSTRACT

Cryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures. The pipeline integrates the implementation and analysis of multi-scale MD simulations for identification, ranking and refinement of lipid binding poses which superpose onto cryo-EM map densities. Thus, LipIDens enables direct integration of experimental and computational structural approaches to facilitate the interpretation of lipid-like cryo-EM densities and to reveal the molecular identities of protein-lipid interactions within a bilayer environment. We demonstrate this by application of our open-source LipIDens code to ten diverse membrane protein structures which exhibit lipid-like densities.


Subject(s)
Membrane Proteins , Molecular Dynamics Simulation , Membrane Proteins/chemistry , Cryoelectron Microscopy , Membrane Lipids , Protein Conformation
15.
Blood Adv ; 7(22): 7007-7016, 2023 11 28.
Article in English | MEDLINE | ID: mdl-37792849

ABSTRACT

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.


Subject(s)
Hematopoietic Stem Cell Transplantation , Myeloproliferative Disorders , Humans , Middle Aged , Transplantation, Homologous , Neoplasm Recurrence, Local , Hematopoietic Stem Cell Transplantation/adverse effects , Acute Disease , Myeloproliferative Disorders/pathology , Chronic Disease , Recurrence , Dendritic Cells/pathology
16.
Adv Sci (Weinh) ; 10(31): e2304632, 2023 11.
Article in English | MEDLINE | ID: mdl-37737614

ABSTRACT

Polylactide (PLA) is the most widely utilized biopolymer in medicine. However, chronic inflammation and excessive fibrosis resulting from its degradation remain significant obstacles to extended clinical use. Immune cell activation has been correlated to the acidity of breakdown products, yet methods to neutralize the pH have not significantly reduced adverse responses. Using a bioenergetic model, delayed cellular changes were observed that are not apparent in the short-term. Amorphous and semi-crystalline PLA degradation products, including monomeric l-lactic acid, mechanistically remodel metabolism in cells leading to a reactive immune microenvironment characterized by elevated proinflammatory cytokines. Selective inhibition of metabolic reprogramming and altered bioenergetics both reduce these undesirable high cytokine levels and stimulate anti-inflammatory signals. The results present a new biocompatibility paradigm by identifying metabolism as a target for immunomodulation to increase tolerance to biomaterials, ensuring safe clinical application of PLA-based implants for soft- and hard-tissue regeneration, and advancing nanomedicine and drug delivery.


Subject(s)
Inflammation , Polyesters , Humans , Polyesters/chemistry , Inflammation/metabolism , Biocompatible Materials , Cytokines/metabolism
17.
Biomater Adv ; 152: 213495, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37301057

ABSTRACT

Primary total joint arthroplasties (TJAs) are widely and successfully applied reconstructive procedures to treat end-stage arthritis. Nearly 50 % of TJAs are now performed in young patients, posing a new challenge: performing TJAs which last a lifetime. The urgency is justified because subsequent TJAs are costlier and fraught with higher complication rates, not to mention the toll taken on patients and their families. Polyethylene particles, generated by wear at joint articulations, drive aseptic loosening by inciting insidious inflammation associated with surrounding bone loss. Down modulating polyethylene particle-induced inflammation enhances integration of implants to bone (osseointegration), preventing loosening. A promising immunomodulation strategy could leverage immune cell metabolism, however, the role of immunometabolism in polyethylene particle-induced inflammation is unknown. Our findings reveal that immune cells exposed to sterile or contaminated polyethylene particles show fundamentally altered metabolism, resulting in glycolytic reprogramming. Inhibiting glycolysis controlled inflammation, inducing a pro-regenerative phenotype that could enhance osseointegration.


Subject(s)
Inflammation , Polyethylene , Humans , Polyethylene/adverse effects , Prostheses and Implants
18.
Int J Surg Case Rep ; 107: 108337, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37210802

ABSTRACT

INTRODUCTION: Intradural Candida Albicans infections are rare with limited number of reports on the pathological condition. Among these reports, patients with these infections had radiographic evidence supporting an intradural infection diagnosis. In this case, the patient displayed radiographic imaging suggestive of an epidural infection, but surgery revealed the infection to be intradural. This case exemplifies the importance of considering intradural infections in future cases of suspected epidural abscesses and highlights antibiotic management of intradural C. albicans infections. PRESENTATION OF CASE: A incarcerated 26-year-old male presented with a rare Candida Albicans infection. He arrived at the hospital unable to walk, and radiographic imaging was consistent with a thoracic epidural abscess. Due to his severe neurologic deficit and spreading edema, surgical intervention was required and revealed no signs of epidural infection. Incision of the dura revealed a purulent material cultured as C. albicans. After six weeks, the intradural infection returned and the patient required another surgery. This operation helped prevent further motor function loss. DISCUSSION: When patients present with a progressive neurologic deficit and radiographic evidence indicative of an epidural abscess, it is important for surgeons to be mindful of a possible intradural infection. If no abscess is found in the epidural space during surgery, opening the dura in patients with worsening neurologic symptoms must be considered to rule out an intradural infection. CONCLUSION: Preoperative suspicion of an epidural abscess can differ from intraoperative diagnosis and looking intradural for an infection can prevent further motor loss.

19.
Front Public Health ; 11: 1117841, 2023.
Article in English | MEDLINE | ID: mdl-37113181

ABSTRACT

The effect of disaster events on increasing drug-involved deaths has been clearly shown in previous literature. As the COVID-19 pandemic led to stay-at-home orders throughout the United States, there was a simultaneous spike in drug-involved deaths around the country. The landscape of a preexisting epidemic of drug-involved deaths in the United States is one which is not geographically homogenous. Given this unequal distribution of mortality, state-specific analysis of changing trends in drug use and drug-involved deaths is vital to inform both care for people who use drugs and local policy. An analysis of public health surveillance data from the state of Louisiana, both before and after the initial stay-at-home order of the COVID-19 pandemic, was used to determine the effect the pandemic may have had on the drug-involved deaths within this state. Using the linear regression analysis of total drug-involved deaths, as well as drug-specific subgroups, trends were measured based on quarterly (Qly) deaths. With the initial stay-at-home order as the change point, trends measured through quarter 1 (Q1) of 2020 were compared to trends measured from quarter 2 (Q2) of 2020 through quarter 3 (Q3) of 2021. The significantly increased rate of change in Qly drug-involved deaths, synthetic opioid-involved deaths, stimulant-involved deaths, and psychostimulant-involved deaths indicates a long-term change following the initial response to the COVID-19 pandemic. Changes in the delivery of mental health services, harm reduction services, medication for opioid use disorder (MOUD), treatment services, withdrawal management services, addiction counseling, shelters, housing, and food supplies further limited drug-involved prevention support, all of which were exacerbated by the new stress of living in a pandemic and economic uncertainty.


Subject(s)
COVID-19 , Drug Overdose , Humans , United States/epidemiology , COVID-19/epidemiology , Pharmaceutical Preparations , Pandemics , Drug Overdose/epidemiology , Louisiana/epidemiology
20.
Global Spine J ; : 21925682231168578, 2023 Apr 03.
Article in English | MEDLINE | ID: mdl-37010029

ABSTRACT

STUDY: Retrospective Study. OBJECTIVE: At the North American Spine Society (NASS) conference, participants may influence spine surgery practices and patient care through their contributions. Therefore, their financial conflicts of interest are of notable interest. This study aims to compare the demographics and payments made to participating surgeons. METHODS: A list of 151 spine surgeons was created based on those who participated in the 2022 NASS conference. Demographic information was obtained from public physician profiles. General payments, research payments, associated research funding, and ownership interest were collected for each physician. Descriptive statistics and two-tailed t-tests were used. RESULTS: In 2021, 151 spine surgeon participants received industry payments, totaling USD 48 294 115. The top 10% of orthopedic surgeons receiving payments accounted for 58.7% of total orthopedic general value, while the top 10% of neurosurgeons accounted for 70.1%. There was no significant difference between these groups' general payment amounts. Surgeons with 21-30 years of experience received the most general funding. There was no difference in funding between surgeons in academic or private settings. For all surgeons, royalties accounted for the largest percentage of the general value exchanged, while food/beverage accounted for the largest percentage of transactions. CONCLUSIONS: Our study found that only years of experience had a positive association with general payments, and most monetary value belonged to a small handful of surgeons. These participants receiving significant money may promote techniques requiring products of companies providing their compensation. Future conferences may require disclosure policy changes so attendees understand the degree of funding participants receive.

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