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1.
Dig Liver Dis ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38987040

ABSTRACT

BACKGROUND: Acute pancreatitis (AP) and venous thromboembolism (VTE) remain common and potentially lethal disease entities. AP might be an important trigger of systemic inflammtion and may activate the coagulation system with increased VTE risk. METHODS: The German nationwide inpatient sample was screened for patients admitted due to AP (ICD-code K85) 2005-2019. AP hospitalizations were stratified for VTE as well as risk-factors and the impact of VTE on in-hospital case-fatality rate were investigated. RESULTS: Overall, 797,364 hospitalizations of patients due to AP (aged in median 56.0 [IQR 44.0-71.0] years), 39.2 % females) were detected in Germany 2005-2019. Incidence of VTE in hospitalized AP patients was 1764.8 per 100,000 hospitalizations (1.8 %) with highest VTE rate between 5th and 6th decade. Cancer (OR 1.656 [95 %CI 1.513-1.812], P < 0.001), any surgery (OR 4.063 [95 %CI 3.854-4.284], P < 0.001), and heart failure (OR 1.723 [95 %CI 1.619-1.833], P < 0.001) were independently associated with VTE occurrence. Case-fatality (8.8 % vs. 2.7 %, P < 0.001) was more than 3-fold higher in AP patients with than without VTE. VTE was associated with increased case-fatality in AP patients (OR 3.925 [95 %CI 3.684-4.181], P < 0.001). CONCLUSIONS: VTE is a life-threatening event in hospitalized AP patients associated with an almost 4-fold increased case-fatality rate. Cancer, any surgery, thrombophilia and heart failure were important risk factors for occurrence of VTE in AP.

2.
J Neurochem ; 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39001667

ABSTRACT

APOE4 encoding apolipoprotein (Apo)E4 is the strongest genetic risk factor for Alzheimer's disease (AD). ApoE is key in intercellular lipid trafficking. Fatty acids are essential for brain integrity and cognitive performance and are implicated in neurodegeneration. We determined the sex- and age-dependent effect of AD and APOE4 on brain free fatty acid (FFA) profiles. FFA profiles were determined by LC-MS/MS in hippocampus, cortex, and cerebellum of female and male, young (≤3 months) and older (>5 months), transgenic APOE3 and APOE4 mice with and without five familial AD (FAD) mutations (16 groups; n = 7-10 each). In the different brain regions, females had higher levels than males of either saturated or polyunsaturated FFAs or both. In the hippocampus of young males, but not of older males, APOE4 and FAD each induced 1.3-fold higher levels of almost all FFAs. In young and older females, FAD and to a less extent APOE4-induced shifts among saturated, monounsaturated, and polyunsaturated FFAs without affecting total FFA levels. In cortex and cerebellum, APOE4 and FAD had only minor effects on individual FFAs. The effects of APOE4 and FAD on FFA levels and FFA profiles in the three brain regions were strongly dependent of sex and age, particularly in the hippocampus. Here, most FFAs that are affected by FAD are similarly affected by APOE4. Since APOE4 and FAD affected hippocampal FFA profiles already at young age, these APOE4-induced alterations may modulate the pathogenesis of AD.

3.
Article in English | MEDLINE | ID: mdl-39019399

ABSTRACT

BACKGROUND: According to person-by-environment models, individual differences in traits may moderate the association between stressors and the development of psychopathology; however, findings in the literature have been inconsistent and little literature has examined adolescent brain structure as a moderator of the effects of stress on adolescent internalizing symptoms. The COVID-19 pandemic presented a unique opportunity to examine the associations between stress, brain structure, and psychopathology. Given links of cortical morphology with adolescent depression and anxiety, the present study investigated whether cortical morphology moderates the relationship between stress from the COVID-19 pandemic on the development of internalizing symptoms in familial high-risk adolescents. METHODS: Prior to the COVID-19 pandemic, 72 adolescents (27M) completed a measure of depressive and anxiety symptoms and underwent magnetic resonance imaging. T1-weighted images were acquired to assess cortical thickness and surface area. Approximately 6-8 months after COVID-19 was declared a global pandemic, adolescents reported their depressive and anxiety symptoms and pandemic-related stress. RESULTS: Adjusting for pre-pandemic depressive and anxiety symptoms and stress, increased pandemic-related stress was associated with increased depressive but not anxiety symptoms. This relationship was moderated by cortical thickness and surface area in the anterior cingulate and cortical thickness in the medial orbitofrontal cortex such that increased stress was only associated with increased depressive and anxiety symptoms among adolescents with lower cortical surface area and higher cortical thickness in these regions. CONCLUSIONS: Results further our understanding of neural vulnerabilities to the associations between stress and internalizing symptoms in general, and during the COVID-19 pandemic in particular.

4.
PLoS Negl Trop Dis ; 18(7): e0012319, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38968318

ABSTRACT

BACKGROUND: Strongyloidiasis is caused by a neglected nematode, manifesting as chronic intestinal infection with potentially severe manifestations. The disease is an emerging problem in non-endemic countries affecting travelers and migrants. Diagnosis of strongyloidiasis is hampered by the lack of standardization and absence of a gold standard. Since adequate direct methods to detect the motile larvae in stool samples are not widely available, other techniques such as serology have been developed. METHODS: We evaluated three commercial ELISA kits (DRG Instruments, IVD Research, and Bordier Affinity Products) to detect IgG antibodies against Strongyloides stercoralis assays utilizing serum samples from travelers with microscopically confirmed strongyloidiasis (n = 50) and other imported helminthic infections (n = 159) as well as healthy controls (n = 50). RESULTS: The DRG, IVD, and Bordier assays showed sensitivities of 58.0%, 64.0%, and 56.0%, respectively. Specificity values were 96.0%, 96.0%, and 92.0% in healthy controls, and 67.3%, 62.9%, and 76.7% in cases with other helminth infections, respectively. Cross-reactions were mostly observed in cases with other nematodes (37.5%, 42.5%, and 20.0%, respectively), but also in trematode (33.3%, 38.1%, and 19.0%, respectively) and in cestode infections (25.0%, 30.0%, and 32.5%, respectively). CONCLUSION: The study demonstrates the diagnostic limitations of serological assays to detect or exclude cases of strongyloidiasis in returning travelers, who frequently present with recent or acute infections.


Subject(s)
Antibodies, Helminth , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G , Sensitivity and Specificity , Serologic Tests , Strongyloides stercoralis , Strongyloidiasis , Strongyloidiasis/diagnosis , Strongyloidiasis/immunology , Humans , Animals , Strongyloides stercoralis/immunology , Strongyloides stercoralis/isolation & purification , Antibodies, Helminth/blood , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin G/blood , Serologic Tests/methods , Male , Adult , Female , Middle Aged , Reagent Kits, Diagnostic/standards , Cross Reactions
5.
Nutrients ; 16(11)2024 May 25.
Article in English | MEDLINE | ID: mdl-38892548

ABSTRACT

We previously demonstrated that diet supplementation with seaweed Sargassum fusiforme (S. fusiforme) prevented AD-related pathology in a mouse model of Alzheimer's Disease (AD). Here, we tested a lipid extract of seaweed Himanthalia elongata (H. elongata) and a supercritical fluid (SCF) extract of S. fusiforme that is free of excess inorganic arsenic. Diet supplementation with H. elongata extract prevented cognitive deterioration in APPswePS1ΔE9 mice. Similar trends were observed for the S. fusiforme SCF extract. The cerebral amyloid-ß plaque load remained unaffected. However, IHC analysis revealed that both extracts lowered glial markers in the brains of APPswePS1ΔE9 mice. While cerebellar cholesterol concentrations remained unaffected, both extracts increased desmosterol, an endogenous LXR agonist with anti-inflammatory properties. Both extracts increased cholesterol efflux, and particularly, H. elongata extract decreased the production of pro-inflammatory cytokines in LPS-stimulated THP-1-derived macrophages. Additionally, our findings suggest a reduction of AD-associated phosphorylated tau and promotion of early oligodendrocyte differentiation by H. elongata. RNA sequencing on the hippocampus of one-week-treated APPswePS1ΔE9 mice revealed effects of H. elongata on, amongst others, acetylcholine and synaptogenesis signaling pathways. In conclusion, extracts of H. elongata and S. fusiforme show potential to reduce AD-related pathology in APPswePS1ΔE9 mice. Increasing desmosterol concentrations may contribute to these effects by dampening neuroinflammation.


Subject(s)
Alzheimer Disease , Dietary Supplements , Disease Models, Animal , Seaweed , Animals , Alzheimer Disease/drug therapy , Seaweed/chemistry , Mice , Hippocampus/drug effects , Hippocampus/metabolism , Plant Extracts/pharmacology , Mice, Transgenic , Sargassum/chemistry , Humans , Plaque, Amyloid , Cholesterol/metabolism , Cholesterol/blood , Male , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , tau Proteins/metabolism
6.
J Neurosurg Spine ; : 1-9, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848601

ABSTRACT

OBJECTIVE: There are limited data about the influence of the lumbar paraspinal muscles on the maintenance of sagittal alignment after pedicle subtraction osteotomy (PSO) and the risk factors for sagittal realignment failure. The authors aimed to investigate the influence of preoperative lumbar paraspinal muscle quality on the postoperative maintenance of sagittal alignment after lumbar PSO. METHODS: Patients who underwent lumbar PSO with preoperative lumbar MRI and pre- and postoperative whole-spine radiography in the standing position were included. Spinopelvic measurements included pelvic incidence, sacral slope, pelvic tilt, L1-S1 lordosis, T4-12 thoracic kyphosis, spinosacral angle, C7-S1 sagittal vertical axis (SVA), T1 pelvic angle, and mismatch between pelvic incidence and L1-S1 lordosis. Validated custom software was used to calculate the percent fat infiltration (FI) of the psoas major, as well as the erector spinae and multifidus (MF). A multivariable linear mixed model was applied to further examine the association between MF FI and the postoperative progression of SVA over time, accounting for repeated measures over time that were adjusted for age, sex, BMI, and length of follow-up. RESULTS: Seventy-seven patients were recruited. The authors' results demonstrated significant correlations between MF FI and the maintenance of corrected sagittal alignment after PSO. After adjustment for the aforementioned parameters, the model showed that the MF FI was significantly associated with the postoperative progression of positive SVA over time. A 1% increase from the preoperatively assessed total MF FI was correlated with an increase of 0.92 mm in SVA postoperatively (95% CI 0.42-1.41, p < 0.0001). CONCLUSIONS: This study included a large patient cohort with midterm follow-up after PSO and emphasized the importance of the lumbar paraspinal muscles in the maintenance of sagittal alignment correction. Surgeons should assess the quality of the MF preoperatively in patients undergoing PSO to identify patients with severe FI, as they may be at higher risk for sagittal decompensation.

7.
Article in English | MEDLINE | ID: mdl-38900623

ABSTRACT

Conventional approaches to dietary assessment are primarily grounded in self-reporting methods or structured interviews conducted under the supervision of dietitians. These methods, however, are often subjective, potentially inaccurate, and time-intensive. Although artificial intelligence (AI)-based solutions have been devised to automate the dietary assessment process, prior AI methodologies tackle dietary assessment in a fragmented landscape (e.g., merely recognizing food types or estimating portion size), and encounter challenges in their ability to generalize across a diverse range of food categories, dietary behaviors, and cultural contexts. Recently, the emergence of multimodal foundation models, such as GPT-4V, has exhibited transformative potential across a wide range of tasks (e.g., scene understanding and image captioning) in various research domains. These models have demonstrated remarkable generalist intelligence and accuracy, owing to their large-scale pre-training on broad datasets and substantially scaled model size. In this study, we explore the application of GPT-4V powering multimodal ChatGPT for dietary assessment, along with prompt engineering and passive monitoring techniques. We evaluated the proposed pipeline using a self-collected, semi free-living dietary intake dataset comprising 16 real-life eating episodes, captured through wearable cameras. Our findings reveal that GPT-4V excels in food detection under challenging conditions without any fine-tuning or adaptation using food-specific datasets. By guiding the model with specific language prompts (e.g., African cuisine), it shifts from recognizing common staples like rice and bread to accurately identifying regional dishes like banku and ugali. Another GPT-4V's standout feature is its contextual awareness. GPT-4V can leverage surrounding objects as scale references to deduce the portion sizes of food items, further facilitating the process of dietary assessment.

8.
Water Res ; 259: 121786, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38875862

ABSTRACT

Rivers are one of the main conduits that deliver plastic from land into the sea, and also act as reservoirs for plastic retention. Yet, our understanding of the extent of river exposure to plastic pollution remains limited. In particular, there has been no comprehensive quantification of the contributions from different river compartments, such as the water surface, water column, riverbank and floodplain to the overall river plastic transport and storage. This study aims to provide an initial quantification of these contributions. We first identified the main relevant transport processes for each river compartment considered. We then estimated the transport and storage terms, by harmonizing available observations on surface, suspended and floodplain plastic. We applied our approach to two river sections in The Netherlands, with a focus on macroplastics (≥2.5 cm). Our analysis revealed that for the studied river sections, suspended plastics account for over 96% of item transport within the river channel, while their relative contribution to mass transport is only 30%-37% (depending on the river section considered). Surface plastics predominantly consisted of heavier items (mean mass: 7.1 g/#), whereas suspended plastics were dominated by lighter fragments (mean mass: 0.1 g/#). Additionally, the majority (98%) of plastic mass was stored within the floodplains, with the river channel accounting for only 2% of the total storage. Our study developed a harmonized approach for quantifying plastic transport and storage across different river compartments, providing a replicable methodology applicable to different regions. Our findings emphasize the importance of systematic monitoring programs across river compartments for comprehensive insights into riverine plastic pollution.


Subject(s)
Environmental Monitoring , Plastics , Rivers , Rivers/chemistry , Netherlands , Environmental Monitoring/methods , Water Pollutants, Chemical/analysis
9.
J Agric Food Chem ; 72(26): 14830-14843, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38888424

ABSTRACT

Beyond the key bitter compound kaempferol 3-O-(2‴-O-sinapoyl-ß-d-sophoroside) previously described in the literature (1), eight further bitter and astringent-tasting kaempferol glucosides (2-9) have been identified in rapeseed protein isolates (Brassica napus L.). The bitterness and astringency of these taste-active substances have been described with taste threshold concentrations ranging from 3.3 to 531.7 and 0.3 to 66.4 µmol/L, respectively, as determined by human sensory experiments. In this study, the impact of 1 and kaempferol 3-O-ß-d-glucopyranoside (8) on TAS2R-linked proton secretion by HGT-1 cells was analyzed by quantification of the intracellular proton index. mRNA levels of bitter receptors TAS2R3, 4, 5, 13, 30, 31, 39, 40, 43, 45, 46, 50 and TAS2R8 were increased after treatment with compounds 1 and 8. Using quantitative UHPLC-MS/MSMRM measurements, the concentrations of 1-9 were determined in rapeseed/canola seeds and their corresponding protein isolates. Depending on the sample material, compounds 1, 3, and 5-9 exceeded dose over threshold (DoT) factors above one for both bitterness and astringency in selected protein isolates. In addition, an increase in the key bitter compound 1 during industrial protein production (apart from enrichment) was observed, allowing the identification of the potential precursor of 1 to be kaempferol 3-O-(2‴-O-sinapoyl-ß-d-sophoroside)-7-O-ß-d-glucopyranoside (3). These results may contribute to the production of less bitter and astringent rapeseed protein isolates through the optimization of breeding and postharvest downstream processing.


Subject(s)
Brassica napus , Glycosides , Kaempferols , Plant Proteins , Receptors, G-Protein-Coupled , Taste , Humans , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Brassica napus/chemistry , Brassica napus/metabolism , Brassica napus/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Proteins/chemistry , Glycosides/chemistry , Plant Extracts/chemistry , Seeds/chemistry , Seeds/metabolism , Brassica rapa/chemistry , Brassica rapa/metabolism
10.
J Neurosurg Spine ; : 1-9, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38875728

ABSTRACT

OBJECTIVE: The paraspinal muscles play an essential role in the stabilization of the lumbar spine. Lumbar paraspinal muscle atrophy has been linked to chronic back pain and degenerative processes within the spinal motion segment. However, the relationship between the different paraspinal muscle groups and facet joint osteoarthritis (FJOA) has not been fully explored. METHODS: In this cross-sectional study, the authors analyzed adult patients who underwent lumbar spinal surgery between December 2014 and March 2023 for degenerative spinal conditions and had preoperative MRI and CT scans. The fatty infiltration (FI) and functional cross-sectional area (fCSA) of the psoas, erector spinae, and multifidus muscles were assessed on axial T2-weighted MR images at the level of the upper endplate of L4 based on established studies and calculated using custom-made software. Intervertebral disc degeneration at each lumbar level was evaluated using the Pfirrmann grading system. The grades from each level were summed to report the cumulative lumbar Pfirrmann grade. Weishaupt classification (0-3) was used to assess FJOA at all lumbar levels (L1 to S1) on preoperative CT scans. The total lumbar FJOA score was determined by adding the Weishaupt grades of both sides at all 5 levels. Correlation and linear regression analyses were conducted to assess the relationship between FJOA and paraspinal muscle parameters. RESULTS: A total of 225 patients (49.7% female) with a median age of 61 (IQR 54-70) years and a median BMI of 28.3 (IQR 25.1-33.1) kg/m2 were included. After adjustment for age, sex, BMI, and the cumulative lumbar Pfirrmann grade, only multifidus muscle fCSA (estimate -4.69, 95% CI -6.91 to -2.46; p < 0.001) and FI (estimate 0.64, 95% CI 0.33-0.94; p < 0.001) were independently predicted by the total FJOA score. A similar relation was seen with individual Weishaupt grades of each lumbar level after controlling for age, sex, BMI, and the Pfirrmann grade of the corresponding level. CONCLUSIONS: Atrophy of the multifidus muscle is significantly associated with FJOA in the lumbar spine. The absence of such correlation for the erector spinae and psoas muscles highlights the unique link between multifidus muscle quality and the degeneration of the spinal motion segment. Further research is necessary to establish the causal link and the clinical implications of these findings.

11.
Eur Spine J ; 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38910167

ABSTRACT

PURPOSE: Surgeons' preoperative expectations of lumbar surgery may be associated with patient-reported postoperative outcomes. METHODS: Preoperatively spine surgeons completed a validated Expectations Survey for each patient estimating amount of improvement expected (range 0-100). Preoperative variables were clinical characteristics, spine-specific disability (ODI), and general health (RAND-12). Two years postoperatively patients again completed these measures and global assessments of satisfaction. Surgeons' expectations were compared to preoperative variables and to clinically important pre- to postoperative changes (MCID) in ODI, RAND-12, and pain and to satisfaction using hierarchical models. RESULTS: Mean expectations survey score for 402 patients was a 57 (IQR 44-68) reflecting moderate expectations. Lower scores were associated with preoperative older age, abnormal gait, sensation loss, vacuum phenomena, foraminal stenosis, prior surgery, and current surgery to more vertebrae (all p ≤ .05). Lower scores were associated postoperatively with not attaining MCID for the ODI (p = .02), RAND-12 (p = .01), and leg pain (p = .01). There were no associations between surgeons' scores and satisfaction (p = .06-.27). 55 patients (14%) reported unfavorable global outcomes and were more likely to have had fracture/infection/repeat surgery (OR 3.2, CI 1.6-6.7, p = .002). CONCLUSION: Surgeons' preoperative expectations were associated with patient-reported postoperative improvement in symptoms and function, but not with satisfaction. These findings are consistent with clinical practice in that surgeons expect some but not complete improvement from surgery and do not anticipate that any particular patient will have markedly unfavorable satisfaction ratings. In addition to preoperative discussions about expectations, patients and surgeons should acknowledge different types of outcomes and address them jointly in postoperative discussions.

12.
Article in English | MEDLINE | ID: mdl-38907582

ABSTRACT

STUDY DESIGN: Retrospective review of a prospective cohort study. OBJECTIVE: To identify the association between Oswestry Disability Index (ODI) subsections and overall improvement 2 years after lumbar surgery for degenerative lumbar spondylolisthesis (DLS). BACKGROUND: DLS often necessitates lumbar surgery. The ODI is a trusted measure for patient-reported outcomes (PROMs) in assessing spinal disorder outcomes. Surgeons utilize the ODI for baseline functional assessment and post-surgery progress tracking. However, it remains uncertain if and how each subsection influences overall ODI improvement. METHODS: This retrospective cohort study analyzed patients who underwent lumbar surgery for DLS between 2016 and 2018. Preoperative and 2-year postoperative ODI assessments were conducted. The study analyzed postoperative subsection scores and defined ODI improvement as ODIpreop-ODIpostop >0. Univariate linear regression was applied, and receiver operating characteristic (ROC) analysis determined cut-offs for subsection changes and postoperative target values to achieve overall ODI improvement. RESULTS: 265 patients (60% female, mean age 67±8 y) with a baseline ODI of 50±6 and a postoperative ODI of 20±7 were included. ODI improvement was noted in 91% (242 patients). Achieving a postoperative target score of ≤2 in subsections correlated with overall ODI improvement. Walking had the highest predictive value for overall ODI improvement (AUC 0.91, sensitivity 79%, specificity 91%). Pain intensity (AUC 0.90, sensitivity 86%, specificity 83%) and changing degree of pain (AUC 0.87, sensitivity 86%, specificity 74%) were also highly predictive. Sleeping had the lowest predictability (AUC 0.79, sensitivity 84%, specificity 65%). Except for sleeping, all subsections had a Youden-index >50%. CONCLUSION: These findings demonstrate how the different ODI subsections associate with overall improvement post-lumbar surgery for DLS. This understanding is crucial for refining preoperative education, addressing particular disabilities, and evaluating surgical efficacy. Additionally, it shows that surgical treatment does not affect all subsections equally.

13.
Eur Spine J ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937347

ABSTRACT

PURPOSE: The literature is scarce in exploring the role of imaging parameters like ultrasound (US) as a biomarker for surgical outcomes. The purpose of this study is to investigate the associations between skin US parameters and revision surgery following spine lumbar fusion. METHODS: Posterior lumbar fusion patients with 2-years follow-up were assessed. Previous fusion or revision not due to adjacent segment disease (ASD) were excluded. Revisions were classified as cases and non-revision were classified as controls. US measurements conducted at two standardized locations on the lumbar back. Skin echogenicity of the average dermal (AD), upper 1/3 of the dermal (UD), lower 1/3 of the dermal (LD), and subcutaneous layer were measured. Echogenicity was calculated with the embedded echogenicity function of our institution's imaging platform (PACS). Statistical significance was set at p < 0.05. RESULTS: A total of 128 patients (51% female, age 62 [54-72] years) were included in the final analysis. 17 patients required revision surgery. AD, UD, and LD echogenicity showed significantly higher results among revision cases 124.5 [IQR = 115.75,131.63], 128.5 [IQR = 125,131.63] and 125.5 [IQR = 107.91,136.50] compared to the control group 114.3 [IQR = 98.83,124.8], 118.5 [IQR = 109.28,127.50], 114 [IQR = 94.20,126.75] respectively. CONCLUSION: The findings of this study demonstrate a significant association between higher echogenicity values in different layers of the dermis and requiring revision surgery. The results provide insights into the potential use of skin US parameters as predictors for revision surgery. These findings may reflect underlying alterations in collagen. Further research is warranted to elucidate the mechanisms driving these associations.

14.
bioRxiv ; 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38883769

ABSTRACT

DNA damage and cytoplasmic DNA induce type-1 interferon (IFN-1) and potentiate responses to immune checkpoint inhibitors. Our prior work found that inhibitors of the DNA damage response kinase ATR (ATRi) induce IFN-1 and deoxyuridine (dU) incorporation by DNA polymerases, akin to antimetabolites. Whether and how dU incorporation is required for ATRi-induced IFN-1 signaling is not known. Here, we show that ATRi-dependent IFN-1 responses require uracil DNA glycosylase (UNG)-initiated base excision repair and STING. Quantitative analyses of nine distinct nucleosides reveals that ATRi induce dU incorporation more rapidly in UNG wild-type than knockout cells, and that induction of IFN-1 is associated with futile cycles of repair. While ATRi induce similar numbers of micronuclei in UNG wild-type and knockout cells, dU containing micronuclei and cytoplasmic DNA are increased in knockout cells. Surprisingly, DNA fragments containing dU block STING-dependent induction of IFN-1, MHC-1, and PD-L1. Furthermore, UNG knockout sensitizes cells to IFN-γ in vitro , and potentiates responses to anti-PD-L1 in resistant tumors in vivo . These data demonstrate an unexpected and specific role for dU-rich DNA in suppressing STING-dependent IFN-1 responses, and show that UNG-deficient tumors have a heightened response to immune checkpoint inhibitors. STATEMENT OF SIGNIFICANCE: Antimetabolites disrupt nucleotide pools and increase dU incorporation by DNA polymerases. We show that unrepaired dU potentiates responses to checkpoint inhibitors in mouse models of cancer. Patients with low tumor UNG may respond to antimetabolites combined with checkpoint inhibitors, and patients with high tumor UNG may respond to UNG inhibitors combined with checkpoint inhibitors.

15.
Cureus ; 16(5): e60058, 2024 May.
Article in English | MEDLINE | ID: mdl-38854208

ABSTRACT

Background Only a few studies have examined the impact of the coronavirus disease 2019 pandemic on spine ambulatory surgeries and changes in trends. Therefore, we investigated trends during the pre-pandemic period and three pandemic stages in patients undergoing lumbar decompression procedures in the ambulatory surgery (AMS) setting. Methodology A total of 2,670 adult patients undergoing one- or two-level lumbar decompression surgery were retrospectively reviewed. Patients were categorized into the following four groups: 1: pre-pandemic (before the pandemic from January 1, 2019, to March 16, 2020); 2: restricted period (when elective surgery was canceled from March 17, 2020, to June 30, 2020); 3: post-restricted 2020 (July 1, 2020, to December 31, 2020, before vaccination); and 4: post-restricted 2021 (January 1, 2021 to December 31, 2021 after vaccination). Simple and multivariable logistic regression analyses as well as retrospective interrupted time series (ITS) analysis were conducted comparing AMS patients in the four periods. Results Patients from the restricted pandemic period were younger and healthier, which led to a shorter length of stay (LOS). The ITS analysis demonstrated a significant drop in mean LOS at the beginning of the restricted period and recovered to the pre-pandemic levels in one year. Multivariable logistic regression analyses indicated that the pandemic was an independent factor influencing the LOS in post-restricted phases. Conclusions As the post-restricted 2020 period itself might be independently influenced by the pandemic, these results should be taken into account when interpreting the LOS of the patients undergoing ambulatory spine surgery in post-restricted phases.

16.
17.
Eur Spine J ; 33(5): 1737-1746, 2024 May.
Article in English | MEDLINE | ID: mdl-38801435

ABSTRACT

PURPOSE: This study aimed to investigate the impact of sarcopenia and lumbar paraspinal muscle composition (PMC) on patient-reported outcomes (PROs) after lumbar fusion surgery with 12-month follow-up (12 M-FU). METHODS: A prospective investigation of patients undergoing elective lumbar fusion was conducted. Preoperative MRI-based evaluation of the cross-sectional area (CSA), the functional CSA (fCSA), and the fat infiltration(FI) of the posterior paraspinal muscles (PPM) and the psoas muscle at level L3 was performed. Sarcopenia was defined by the psoas muscle index (PMI) at L3 (CSAPsoas [cm2]/(patients' height [m])2). PROs included Oswestry Disability Index (ODI), 12-item Short Form Healthy Survey with Physical (PCS-12) and Mental Component Scores (MCS-12) and Numerical Rating Scale back and leg (NRS-L) pain before surgery and 12 months postoperatively. Univariate and multivariable regression determined associations among sarcopenia, PMC and PROs. RESULTS: 135 patients (52.6% female, 62.1 years, BMI 29.1 kg/m2) were analyzed. The univariate analysis demonstrated that a higher FI (PPM) was associated with worse ODI outcomes at 12 M-FU in males. Sarcopenia (PMI) and higher FI (PPM) were associated with worse ODI and MCS-12 at 12 M-FU in females. Sarcopenia and higher FI of the PPM are associated with worse PCS-12 and more leg pain in females. In the multivariable analysis, a higher preoperative FI of the PPM (ß = 0.442; p = 0.012) and lower FI of the psoas (ß = -0.439; p = 0.029) were associated with a worse ODI at 12 M-FU after adjusting for covariates. CONCLUSIONS: Preoperative FI of the psoas and the PPM are associated with worse ODI outcomes one year after lumbar fusion. Sarcopenia is associated with worse ODI, PCS-12 and NRS-L in females, but not males. Considering sex differences, PMI and FI of the PPM might be used to counsel patients on their expectations for health-related quality of life after lumbar fusion.


Subject(s)
Lumbar Vertebrae , Paraspinal Muscles , Patient Reported Outcome Measures , Sarcopenia , Spinal Fusion , Humans , Male , Female , Sarcopenia/diagnostic imaging , Middle Aged , Lumbar Vertebrae/surgery , Lumbar Vertebrae/diagnostic imaging , Prospective Studies , Aged , Paraspinal Muscles/diagnostic imaging , Follow-Up Studies , Awards and Prizes
18.
Br J Surg ; 111(5)2024 May 03.
Article in English | MEDLINE | ID: mdl-38713609

ABSTRACT

BACKGROUND: Data on the incidence and clinical relevance of gallstones in patients with suspected acute alcoholic pancreatitis are lacking and are essential to minimize the risk of recurrent acute pancreatitis. The aim of this study was to assess the incidence of gallstones and the associated rate of recurrent acute pancreatitis in patients with presumed acute alcoholic pancreatitis. METHODS: Between 2008 and 2019, 23 hospitals prospectively enrolled patients with acute pancreatitis. Those diagnosed with their first episode of presumed acute alcoholic pancreatitis were included in this study. The term gallstones was used to describe the presence of cholelithiasis or biliary sludge found during imaging. The primary outcome was pancreatitis recurrence during 3 years of follow-up. RESULTS: A total of 334 patients were eligible for inclusion, of whom 316 were included in the follow-up analysis. Gallstone evaluation, either during the index admission or during follow-up, was performed for 306 of 334 patients (91.6%). Gallstones were detected in 54 patients (17.6%), with a median time to detection of 6 (interquartile range 0-42) weeks. During follow-up, recurrent acute pancreatitis occurred in 121 of 316 patients (38.3%), with a significantly higher incidence rate for patients with gallstones compared with patients without gallstones (59% versus 34.2% respectively; P < 0.001), while more patients with gallstones had stopped drinking alcohol at the time of their first recurrence (41% versus 24% respectively; P = 0.020). Cholecystectomy was performed for 19 patients with gallstones (36%). The recurrence rate was lower for patients in the cholecystectomy group compared with patients who did receive inadequate treatment or no treatment (5/19 versus 19/34 respectively; P = 0.038). CONCLUSION: Gallstones were found in almost one in every five patients diagnosed with acute alcoholic pancreatitis. Gallstones were associated with a higher rate of recurrent pancreatitis, while undergoing cholecystectomy was associated with a reduction in this rate.


Subject(s)
Gallstones , Pancreatitis, Alcoholic , Recurrence , Humans , Gallstones/complications , Gallstones/surgery , Gallstones/epidemiology , Male , Female , Middle Aged , Pancreatitis, Alcoholic/complications , Pancreatitis, Alcoholic/epidemiology , Aged , Incidence , Prospective Studies , Adult , Cholecystectomy , Follow-Up Studies
19.
J Stroke Cerebrovasc Dis ; 33(8): 107786, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38782166

ABSTRACT

OBJECTIVES: Periodic imaging follow-up for patients with unruptured intracranial aneurysms (UIA) is crucial, as studies indicate higher rupture risk with aneurysm growth. However, few studies address patient adherence to follow-up recommendations. This study aims to identify compliance rates and factors influencing follow-up adherence. METHODS: Patients with a UIA were identified from our institution's database from 2011-2021. Follow-up imaging (CT/MR Angiogram) was advised at specific intervals. Patients were categorized into compliant and non-compliant groups based on first-year compliance. Factors contributing to compliance were assessed through multivariate logistic regression. Phone interviews were conducted with non-compliant patients to understand reasons for non-adherence. RESULTS: Among 923 UIA diagnosed patients, 337 were randomly selected for analysis. The median follow-up period was 1.4 years, with a 42% first-year compliance rate. The mean aneurysm size was 3.3 mm. Five patients had a rupture during follow-up, of which 4 died. Compared with patients consulting specialists at the initial diagnosis, those seen by non-specialists exhibited lower compliance (OR 0.25, p < 0.001). Loss to follow-up was greatest during transition from emergency service to specialist appointments. Patients who spoke languages other than English exhibited poorer compliance than those speaking English (OR 0.20, p = 0.01). CONCLUSIONS: Significant amounts of UIA patients at low rupture risk were lost to follow-up before seeing UIA specialists. Main non-compliance factors include inadequate comprehension of follow-up instructions, poor care transfer from non-specialists to specialist, and insurance barriers.

20.
Article in English | MEDLINE | ID: mdl-38717315

ABSTRACT

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To analyze the relationship of abdominal aortic calcification (AAC) and a reduction in the cross-sectional area (CSA) and the fatty infiltration (FI) of the paravertebral muscles in patients undergoing lumbar fusion surgery. BACKGROUND: Both AAC and paraspinal muscle degeneration have been shown to be associated with poorer outcomes after surgical treatment of degenerative diseases of the lumbar spine. However, there is a lack of data on the association between AAC and paraspinal muscle changes in patients undergoing spine surgery. METHODS: We retrospectively analyzed patients undergoing lumbar fusion for degenerative spinal pathologies. Muscular and spinal degeneration were measured on magnetic resonance imaging (MRI). AAC was classified on lateral lumbar radiographs. The association of AAC and paraspinal muscle composition was assessed by a multivariate regression analysis adjusted for age, sex, body mass index (BMI), comorbidities, and lumbar degeneration. RESULTS: A total of 301 patients was included. Patients with AAC showed significantly higher degrees of intervertebral disc and facet joint degeneration as well as higher total endplate scores at the L3/4 level. The univariable regression analysis showed a significant positive correlation between the degree of AAC and the FI of the erector spinae (b=0.530, P<0.001) and multifidus (b=0.730, P<0.001). The multivariable regression analysis showed a significant positive correlation between the degree of AAC and the FI of the erector spinae (b=0.270, P=0.006) and a significant negative correlation between the degree of AAC and the CSA of the psoas muscle (b=-0.260, P=0.003). CONCLUSION: This study demonstrates a significant and independent association between AAC and degeneration of the erector spinae and the psoas muscles in patients undergoing lumbar fusion. As both AAC and degeneration of paraspinal muscles impact postoperative outcomes negatively, preoperative assessment of AAC may aid in identifying patients at higher risk after lumbar surgery.

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