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1.
One Health ; 19: 100890, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39314246

ABSTRACT

With modern international trade and the rapid movement of people, animals, and food products, today's risks to food security are increasing worldwide. It is clear that human health, animal health, environmental health, and agriculture are inextricable linked. Food security problems in one sector often adversely impact multiple other sectors. Food security threats are often complex with many factors influencing the emergence of new threats. As multiple US governmental agencies share responsibilities for food security threat mitigation, we need to find new ways for the numerous food security scientific disciplines and agencies to forge new effective research collaborations in meeting these threats. This special issue of the journal One Health seeks to give examples of such research. It represents a collection of scientific reports from oral and poster presentations delivered at the April 21-23, 2024, "International Symposium on One Health Research: Improving Food Security and Resilience" in Galveston, Texas.

2.
J Speech Lang Hear Res ; : 1-16, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39259879

ABSTRACT

PURPOSE: The purpose of the present study is to (a) provide quantitative data on the growth of levator veli palatini (LVP), velopharyngeal (VP), and craniofacial dimensions in children under 12 months while controlling for corrected age and sex and (b) compare variability within age and sex groups. METHOD: Magnetic resonance imaging scans of 75 infants between 0 and 12 months were measured and divided into four age groups. These data were obtained as part of a larger retrospective study. Following exclusion criteria, scans were analyzed, and dependent variables were obtained. RESULTS: There was a statistically significant (p < .0001) difference between corrected age groups on LVP muscle, VP, and craniofacial variables while controlling for sex. Significant growth effects were observed for LVP length (p < .0001), extravelar length (p < .0001), intravelar length (p = .048), midline thickness (p = .0001), origin-origin distance (p < .0001), velar length (p < .0001), velar thickness (p = .003), nasion-sella turcica distance (p < .0001), sella turcica-basion distance (p < .0001), and hard palate length (p < .0001). Significant sex effects were observed for pharyngeal depth (p = .026) and effective VP ratio (p = .014). When age was treated as a continuous variable, similar results were observed for all variables except pharyngeal depth. Within-group comparisons revealed the most variability occurs between 3 and 5.99 months for LVP and craniofacial variables and between 9 and 11.99 months of age for VP variables. Male participants demonstrated greater variability than female participants. CONCLUSIONS: Differences were observed in LVP, VP, and craniofacial variables in children under 12 months while controlling for sex. Males demonstrated larger values and greater variability for most variables.

3.
Article in English | MEDLINE | ID: mdl-39257341

ABSTRACT

OBJECTIVES: RA-associated interstitial lung disease (RA-ILD) includes multiple subtypes with varying histopathology, prognosis, and potential treatments. Limited research has investigated risk factors for different RA-ILD subtypes. Therefore, we examined demographic, serologic, and lifestyle associations with RA-ILD subtypes. METHODS: We systematically identified RA-ILD cases and RA-noILD controls in the Brigham RA Sequential Study and Mass General Brigham Biobank RA cohort. We determined RA-ILD subtype (usual interstitial pneumonia [UIP], nonspecific interstitial pneumonia [NSIP], and other/indeterminate) through chest high-resolution computed tomography imaging pattern. We investigated associations between demographic, lifestyle, and serologic factors and major RA-ILD subtypes using multivariable logistic regression. RESULTS: Among 3328 RA patients, we identified 208 RA-ILD cases and 547 RA-noILD controls. RA-UIP was associated with older age (OR 1.03 per year, 95%CI 1.01 to 1.05), male sex (OR 2.15, 95%CI 1.33 to 3.48), and seropositivity (OR 2.08 95%CI 1.24 to 3.48) while RA-NSIP was significantly associated only with seropositive status (OR 3.21, 95%CI 1.36 to 7.56). Non-fibrotic ILDs were significantly associated with smoking (OR 2.81, 95%CI 1.52 to 5.21). Having three RA-ILD risk factors (male, seropositive, smoking) had an OR of 6.89 (96%CI 2.41 to 19.7) for RA-UIP compared to having no RA-ILD risk factors. CONCLUSIONS: Older age, seropositivity, and male sex were strongly associated with RA-UIP while RA-related autoantibodies were associated with RA-NSIP. These findings suggest RA-ILD sex differences may be driven by RA-UIP and emphasizes the importance of further studies to clarify RA-ILD heterogeneity and optimize screening and treatment approaches.

4.
Surg Clin North Am ; 104(5): 1083-1093, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39237165

ABSTRACT

Minimally invasive procedures minimize trauma to the human body while maintaining satisfactory therapeutic results. Minimally invasive pancreas surgery (MIPS) was introduced in 1994, but questions regarding its efficacy compared to an open approach were widespread. MIPS is associated with several perioperative advantages while maintaining oncological standards when performed by surgeons with a robust training regimen and frequent practice. Future research should focus on addressing learning curve discrepancies while identifying factors associated with shortening the time needed to attain technical proficiency.


Subject(s)
Minimally Invasive Surgical Procedures , Pancreatectomy , Humans , Minimally Invasive Surgical Procedures/methods , Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Laparoscopy/methods , Robotic Surgical Procedures/methods , Pancreas/surgery , Learning Curve
5.
Br J Sports Med ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39237264

ABSTRACT

Multiligament knee injuries (MLKIs) represent a broad spectrum of pathology with potentially devastating consequences. Currently, disagreement in the terminology, diagnosis and treatment of these injuries limits clinical care and research. This study aimed to develop consensus on the nomenclature, diagnosis, treatment and rehabilitation strategies for patients with MLKI, while identifying important research priorities for further study. An international consensus process was conducted using validated Delphi methodology in line with British Journal of Sports Medicine guidelines. A multidisciplinary panel of 39 members from 14 countries, completed 3 rounds of online surveys exploring aspects of nomenclature, diagnosis, treatment, rehabilitation and future research priorities. Levels of agreement (LoA) with each statement were rated anonymously on a 5-point Likert scale, with experts encouraged to suggest modifications or additional statements. LoA for consensus in the final round were defined 'a priori' if >75% of respondents agreed and fewer than 10% disagreed, and dissenting viewpoints were recorded and discussed. After three Delphi rounds, 50 items (92.6%) reached consensus. Key statements that reached consensus within nomenclature included a clear definition for MLKI (LoA 97.4%) and the need for an updated MLKI classification system that classifies injury mechanism, extent of non-ligamentous structures injured and the presence or absence of dislocation. Within diagnosis, consensus was reached that there should be a low threshold for assessment with CT angiography for MLKI within a high-energy context and for certain injury patterns including bicruciate and PLC injuries (LoA 89.7%). The value of stress radiography or intraoperative fluoroscopy also reached consensus (LoA 89.7%). Within treatment, it was generally agreed that existing literature generally favours operative management of MLKI, particularly for young patients (LoA 100%), and that single-stage surgery should be performed whenever possible (LoA 92.3%). This consensus statement will facilitate clinical communication in MLKI, the care of these patients and future research within MLKI.

6.
J Sports Sci Med ; 23(1): 537-547, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39228778

ABSTRACT

Sports injuries pose significant challenges in athlete welfare and team dynamics, particularly in high-intensity sports like soccer. This study used machine learning algorithms to assess non-contact injury risk in professional male soccer players from physiological and mechanical load variables. Twenty-five professional male soccer players with a first-time, non-contact muscle injury were included in this study. Recordings of external load (speed, distance, and acceleration/deceleration data) and internal load (heart rate) were obtained during all training sessions and official matches over a 4-year period. Machine learning model training and evaluation features were calculated for each of nine different metrics for a 28-day period prior to the injury and an equal-length baseline epoch. The acute surge in the values of each workload metric was quantified by the deviation of maximum values from the average, while the variations of cumulative workload over the last four weeks preceding injury were also calculated. Seven features were selected by the model as prominent estimators of injury incidence. Three of the features concerned acute load deviations (number of sprints, training load score-incorporating heart rate and muscle load- and time of heart rate at the 90-100% of maximum). The four cumulative load features were (total distance, high speed and sprint running distance and training load score). The accuracy of the muscle injury risk assessment model was 0.78, with a sensitivity of 0.73 and specificity of 0.85. Our model achieved high performance in injury risk detection using a limited number of training load variables. The inclusion, for the first time, of heart rate related variables in an injury risk assessment model highlights the importance of physiological overload as a contributor to muscle injuries in soccer. By identifying the important parameters, coaches may prevent muscle injuries by controlling surges of training load during training and competition.


Subject(s)
Athletic Injuries , Heart Rate , Machine Learning , Running , Soccer , Humans , Soccer/injuries , Soccer/physiology , Male , Athletic Injuries/prevention & control , Risk Assessment , Running/injuries , Running/physiology , Young Adult , Physical Conditioning, Human/adverse effects , Physical Conditioning, Human/methods , Acceleration , Adult , Muscle, Skeletal/injuries , Muscle, Skeletal/physiology
7.
Nutrients ; 16(17)2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39275230

ABSTRACT

The aim of this study was to investigate the effects of a supplement rich in ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) and antioxidant vitamins on physical performance and body composition following a period of high-intensity functional training (HIFT). Nineteen healthy young adults (nine males, ten females) underwent an 8-week HIFT program (3 days·week-1) where they were randomized 1:1 into either the supplement group (SG)-n = 10, receiving a 20 mL daily dose of a dietary cocktail formula (Neuroaspis™ PLP10) containing a mixture of ω-3 and ω-6 PUFAs (12,150 mg), vitamin A (0.6 mg), vitamin E (22 mg), and γ-tocopherol (760 mg)-or the placebo group (PG)-n = 9, receiving a 20 mL daily dose of virgin olive oil. Body composition, cardiorespiratory fitness, muscle strength, and muscle endurance were assessed before and after the training period. Body mass did not change, but muscle mass increased by 1.7 ± 1.9% or 0.40 ± 0.53 kg in the SG (p = 0.021) and decreased by 1.2 ± 1.6% or 0.28 ± 0.43 kg (p = 0.097) in the PG, compared with baseline. VO2max, vertical jump, squat 1RM, bench press 1RM, and muscle endurance increased similarly in both groups. The effects of HIFT on physical performance parameters, muscle damage, and inflammation indices were not affected by the supplementation. In conclusion, HIFT combined with high doses of ω-3 and ω-6 PUFAs and antioxidant vitamins resulted in a small but significant increase in muscle mass and fat reduction compared with HIFT alone.


Subject(s)
Antioxidants , Body Composition , Dietary Supplements , Fatty Acids, Omega-3 , Fatty Acids, Omega-6 , Humans , Male , Female , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-6/administration & dosage , Antioxidants/administration & dosage , Double-Blind Method , Body Composition/drug effects , Young Adult , Adult , Muscle Strength/drug effects , Exercise/physiology , Vitamins/administration & dosage , Vitamins/pharmacology , Cardiorespiratory Fitness/physiology , Vitamin E/administration & dosage , Vitamin E/pharmacology , High-Intensity Interval Training/methods
8.
Article in English | MEDLINE | ID: mdl-39289537

ABSTRACT

BACKGROUND: Staging patients with high-risk prostate cancer (HRPCa) with conventional imaging of computed tomography (CT) and bone scintigraphy (BS) is suboptimal. Therefore, we aimed to compare the accuracy of whole-body magnetic resonance imaging (WBMRI) with conventional imaging to stage patients with HRPCa. METHODS: We prospectively enrolled patients with newly diagnosed HRPCa (prostate-specific antigen ≥20 ng/ml and/or Grade Group ≥4). Patients underwent BS, CT of the abdomen and pelvis, and WBMRI within 30 days of evaluation. The primary endpoint was the diagnostic performances of detecting metastatic disease to the lymph nodes and bone for WBMRI and conventional imaging. The reference standard was defined by histopathology or by all available clinical information at 6 months of follow-up. To compare diagnostic tests, Exact McNemar's test and area under the curve (AUC) of the receiver operating characteristics curves were utilized. RESULTS: Among 92 patients enrolled, 15 (16.3%) and 8 (8.7%) patients were found to have lymphatic and bone metastases, respectively. The sensitivity, specificity, and accuracy of WBMRI in detecting lymphatic metastases were 0.60 (95% confidence interval 0.32-0.84), 0.84 (0.74-0.92), and 0.80 (0.71-0.88), respectively, while CT were 0.20 (0.04-0.48), 0.92 (0.84-0.97), and 0.80 (0.71-0.88). The sensitivity, specificity, and accuracy of WBMRI to detect bone metastases were 0.25 (0.03-0.65), 0.94 (0.87-0.98), and 0.88 (0.80-0.94), respectively, while CT and BS were 0.12 (0-0.53), 0.94 (0.87-0.98), and 0.87 (0.78-0.93). For evaluating lymphatic metastases, WBMRI demonstrated a higher sensitivity (p = 0.031) and discrimination compared to CT (0.72 versus 0.56, p = 0.019). CONCLUSIONS: For staging patients with HRPCa, WBMRI outperforms CT in the detection of lymphatic metastases and performs as well as CT and BS in the detection of bone metastases. Further studies are needed to assess the cost effectiveness of WBMRI and the utility of combined PSMA PET and WBMRI.

10.
Pharmacology ; : 1-13, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39134007

ABSTRACT

INTRODUCTION: In our earlier efforts to establish gut-brain axis during alcohol use disorder (AUD), we have demonstrated that supplementation of C57BL/6J male mice with 8 mg/mL sodium butyrate, a major short-chain fatty acid, in drinking water reduced ethanol intake and neuroinflammatory response in antibiotic (ABX)-enhanced voluntary binge-like alcohol consumption model, drinking in the dark (DID). METHODS: To further evaluate the preclinical potential of SB, we have set a dose-escalation study in C57BL/6J male mice to test effects of ad libitum 20 mg/mL SB and 50 mg/mL SB and their combinations with ABX in the DID procedure for 4 weeks. Effects of these SB concentrations on ethanol consumption and bodily parameters were determined for the duration of the treatments. At the end of study, blood, liver, and intestinal tissues were collected to study any potential adverse effects ad to measure blood ethanol concentrations. RESULTS: Increasing SB concentrations in the drinking water caused a loss in the protective effect against ethanol consumption and produced adverse effects on body and liver weights, reduced overall liquid intake. The hypothesis that these effects were due to aversion to SB smell/taste at these high concentrations were further tested in a follow up proof-of-concept study with intragastric gavage administration of SB. The higher gavage dose (320 mg/kg) caused reduction in ethanol consumption without any adverse effects. CONCLUSION: Overall, these findings added more support for the therapeutic potential of SB in management of AUD, given a proper form of administration.

11.
ACS Macro Lett ; 13(9): 1133-1138, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39145595

ABSTRACT

The development of modern optoelectronic devices increases the need for lightweight and flexible transparent conductors. It is thus essential to develop new eco-friendly materials that can be easily processed for the fabrication of such devices. For this purpose, the synthesis of self-doped, highly conducting, transmissive, and water-processable polythiophene derivatives was performed via the direct heteroarylation polymerization method and a protection/deprotection strategy. Stable conductivities up to 1000 S cm-1 have been obtained. Champion materials (P1 and P7) were scaled and processed via the roll-to-roll compatible slot-die coating method to demonstrate their large area applicability. The best coated films exhibited optical transmittance greater than 79% at 550 nm with sheet resistances of 116 Ω â–¡-1. These values are comparable to indium-tin oxide on plastic and thus present a viable alternative to metal oxide-based electrodes.

12.
Lipids Health Dis ; 23(1): 242, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39123208

ABSTRACT

It had been observed that homozygous albumin knockout mice (Alb-/-) exhibit low plasma free fatty acid (FFA) concentration and improved blood glucose regulation. However, it was not yet known to what extent heterozygous albumin knockout (Alb+/-) mice would display a similar phenotype. Alb-/-, Alb+/-, and wild-type (WT) female mice were studied on a low-fat diet (LFD) or high-fat diet (HFD). On both diets, decreased plasma FFA concentration, and improved glucose tolerance test were observed in Alb-/-, but not in Alb+/-, compared to WT. Plasma adiponectin concentration showed greater elevation in Alb-/- than Alb+/-. Consistent with that, adiponectin gene expression was significantly higher in Alb-/- mice than in Alb+/- and WT mice. A dose-dependent response was observed for hepatic Acadl gene expression showing higher Acadl gene expression in Alb-/- mice than in Alb+/- and WT mice. In conclusion, although female Alb+/- mice exhibited some slight differences from WT mice (e.g., increased plasma adiponectin and hepatic Acadl gene expression), Alb+/- mice did not exhibit improved glucoregulation in comparison to WT mice, indicating that a minor suppression of albumin expression is not sufficient to improve glucoregulation. Furthermore, it is now clear that although the response of female mice to HFD might be unique from how males generally respond, still the complete albumin deficiency in Alb-/- mice and the associated FFA reduction is capable of improving glucoregulation in females on this diet. The present results have implications for the role of albumin and FFA in the regulation of metabolism.


Subject(s)
Adiponectin , Albumins , Blood Glucose , Diet, High-Fat , Fatty Acids, Nonesterified , Mice, Knockout , Animals , Female , Adiponectin/genetics , Adiponectin/metabolism , Adiponectin/blood , Mice , Fatty Acids, Nonesterified/blood , Fatty Acids, Nonesterified/metabolism , Diet, High-Fat/adverse effects , Albumins/metabolism , Albumins/genetics , Blood Glucose/metabolism , Liver/metabolism , Diet, Fat-Restricted , Glucose Tolerance Test , Serum Albumin/metabolism , Serum Albumin/genetics , Gene Expression Regulation , Mice, Inbred C57BL
13.
Cell Rep Med ; 5(8): 101668, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39094579

ABSTRACT

We describe the molecular-level composition of polyclonal immunoglobulin G (IgG) anti-spike antibodies from ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, vaccination, or their combination ("hybrid immunity") at monoclonal resolution. Infection primarily triggers S2/N-terminal domain (NTD)-reactive antibodies, whereas vaccination mainly induces anti-receptor-binding domain (RBD) antibodies. This imprint persists after secondary exposures wherein >60% of ensuing hybrid immunity derives from the original IgG pool. Monoclonal constituents of the original IgG pool can increase breadth, affinity, and prevalence upon secondary exposures, as exemplified by the plasma antibody SC27. Following a breakthrough infection, vaccine-induced SC27 gained neutralization breadth and potency against SARS-CoV-2 variants and zoonotic viruses (half-maximal inhibitory concentration [IC50] ∼0.1-1.75 nM) and increased its binding affinity to the protective RBD class 1/4 epitope (dissociation constant [KD] < 5 pM). According to polyclonal escape analysis, SC27-like binding patterns are common in SARS-CoV-2 hybrid immunity. Our findings provide a detailed molecular definition of immunological imprinting and show that vaccination can produce class 1/4 (SC27-like) IgG antibodies circulating in the blood.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Immunoglobulin G , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , Immunoglobulin G/immunology , Immunoglobulin G/blood , Humans , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/immunology , Antibodies, Viral/blood , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , Epitopes/immunology , Female , Antibodies, Monoclonal/immunology , Male
14.
Proc Natl Acad Sci U S A ; 121(35): e2408889121, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39167600

ABSTRACT

WD40 Repeat Domain 5 (WDR5) is a highly conserved nuclear protein that recruits MYC oncoprotein transcription factors to chromatin to stimulate ribosomal protein gene expression. WDR5 is tethered to chromatin via an arginine-binding cavity known as the "WIN" site. Multiple pharmacological inhibitors of the WDR5-interaction site of WDR5 (WINi) have been described, including those with picomolar affinity and oral bioavailability in mice. Thus far, however, WINi have only been shown to be effective against a number of rare cancer types retaining wild-type p53. To explore the full potential of WINi for cancer therapy, we systematically profiled WINi across a panel of cancer cells, alone and in combination with other agents. We report that WINi are unexpectedly active against cells derived from both solid and blood-borne cancers, including those with mutant p53. Among hematologic malignancies, we find that WINi are effective as a single agent against leukemia and diffuse large B cell lymphoma xenograft models, and can be combined with the approved drug venetoclax to suppress disseminated acute myeloid leukemia in vivo. These studies reveal actionable strategies for the application of WINi to treat blood-borne cancers and forecast expanded utility of WINi against other cancer types.


Subject(s)
Hematologic Neoplasms , Xenograft Model Antitumor Assays , Humans , Animals , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/genetics , Hematologic Neoplasms/metabolism , Mice , Cell Line, Tumor , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use
15.
Sci Rep ; 14(1): 18897, 2024 08 14.
Article in English | MEDLINE | ID: mdl-39143116

ABSTRACT

There is growing evidence that a relationship exists between mental and emotional wellbeing and the gut microbiota. Little is known regarding how the microbiota reacts to repeated acute stress events in dogs, and whether it is a predictor of stress response. In this study, we explored the impact on the gut microbiota and digestive health with two common events many pet dogs find stressful. Twenty healthy adult dogs, living within a colony, were exposed to either car travel or separation three times across eight-week intervals. Faecal samples were collected 24 h before, within 24 h, and 24-48 h after. Faecal quality and pH, and microbiota diversity and composition were analysed in context with wider published work on physiological stress measures. No significant changes were observed in faecal quality or pH with either stress event at any timepoint, indicating all pets remained in good digestive health. Microbiota analysis demonstrated no significant impact on alpha or beta diversity with either stressor. Microbial signatures previously linked to stress were not identified in these dogs and no changes were observed in the functional gut composition. Irrespective of whether the pet was considered "stressed" (i.e., exhibited an increase in serum cortisol), there was no effect on the microbiota and no taxa were predictive of stress response. Collectively, this work demonstrates, for this population, certain acute stress events have no meaningful impact on the canine gut microbiota, and it has no impact on the associated stress response.


Subject(s)
Feces , Gastrointestinal Microbiome , Stress, Psychological , Animals , Dogs , Feces/microbiology , Stress, Psychological/microbiology , Male , Female , Stress, Physiological
16.
J Surg Oncol ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39165230

ABSTRACT

BACKGROUND: In patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high-risk features on histopathologic examination. We evaluated the interaction between post-NAT lymph node metrics and AC receipt on survival. METHODS: Patients who received NAT followed by pancreatectomy (2010-2020) at seven centers were reviewed. Overall survival (OS) in patients receiving AC or not was stratified by lymph node positivity (LNP) or lymph node ratio (LNR) dichotomized at 0.1. Cox models evaluated the independent association between these nodal metrics, AC receipt, and OS. RESULTS: Of 464 patients undergoing NAT and resection, 264 (57%) received AC. Patients selected for AC were younger (median 63 vs. 67 years; p < 0.001), received shorter duration of NAT (2.8 vs. 3.2 months; p = 0.01), had fewer postoperative complications (Clavien-Dindo grade > 3: 1.2% vs. 11.7%; p < 0.001), and lower rates of pathologic complete response (4% vs. 11%; p = 0.01). The median number of nodes evaluated was similar between cohorts (n = 20 in both; p = 0.9). Post-NAT LNP rates were not different, and median LNR was 0.1, in AC and non-AC cohorts. Both LNP (hazard ratio [HR]: 2.1, p < 0.001) and LNR (0 < LNR ≤ 0.1: HR: 1.98, p = 0.002; LNR > 0.1: HR 2.46, p < 0.001) were independently associated with OS on Cox modeling, although receipt of AC was not associated with improved OS (median 30.6 vs. 29.4 months; p = 0.2). In patients with LNR > 0.1, receipt of AC was associated with significantly longer OS compared to non-AC (24 vs. 20 months, respectively; p = 0.04). CONCLUSIONS: LNR following NAT, not simply nodal positivity, may be useful to refine selection of AC in resected PDAC.

17.
J Surg Res ; 302: 611-620, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39182442

ABSTRACT

INTRODUCTION: Surgery followed by pathology-guided adjuvant therapy is standard treatment for colon cancer. Data from the FOxTROT clinical trial showed potential benefit of a 6-wk neoadjuvant chemotherapy (NACT) in T3/T4 patients. The present study evaluated real-world outcomes of neoadjuvant therapy in a national cohort of patients with resectable colon cancer. METHODS: 169,120 patients with clinical stage I, II, or III colon cancer from the National Cancer Database registry were included. Patients were categorized as having received neoadjuvant therapy followed by surgery (NACT), surgery then adjuvant chemotherapy (AC), or surgery alone. Factors associated with treatment sequencing and outcomes were assessed. RESULTS: Of identified patients, 1.4% received NACT including 0.5% of stage I, 1.8% of stage II, and 3.0% of stage III. For stage I, 5-y overall survival (OS) was 74.7% after AC, 62.2% after NACT, and 76.4% after SA. For stage II, 5-y OS was 73.2% after AC, 66.8% after NACT, and 64.3% after SA. For stage III, 5-y OS was 67.3% after AC, 67.7% after NACT, and 42.4% after SA. Cox proportional-hazards model suggested NACT had worse outcomes versus AC in clinical stages I (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.39-1.85, P < 0.01) and II (HR = 1.37, 95% CI 1.23-1.52, P < 0.01). In stage III, there was no difference in OS between NACT and AC (HR = 1.1, 95% CI 0.99-1.22, P = 0.05). CONCLUSIONS: In a real-world national cohort of patients with resectable colon cancer, NACT had no OS benefit over AC. Future studies should examine which subset of patients might benefit from neoadjuvant approaches.

18.
Am J Sports Med ; 52(10): 2532-2540, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39101611

ABSTRACT

BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in the treatment of knee cartilage defects, although limited research is available on its longer term (≥10 years) sustainability in the patellofemoral joint. PURPOSE: To report the clinical and radiological outcomes at ≥10 years in a prospectively recruited cohort of patients undergoing MACI in the patellofemoral joint and compare outcomes in patients undergoing MACI on the patella versus the trochlea. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The current study prospectively enrolled 95 patients who underwent patellofemoral MACI, of whom 29 (13 patella, 16 trochlea) underwent concomitant tibial tubercle osteotomy. Patients were assessed preoperatively and at 2, 5, and ≥10 years using a range of patient-reported outcome measures (PROMs) including the Knee injury and Osteoarthritis Outcome Score, the 36-item Short Form Health Survey, and the frequency and severity of knee pain as well as patient satisfaction, full active knee flexion and extension, and peak isokinetic knee extensor and flexor torques. High-resolution magnetic resonance imaging (MRI) was performed to assess pertinent graft parameters, as well as determine an overall MRI composite score, per the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system. Results were analyzed according to the graft location (patella or trochlea). RESULTS: Of the 95 patients recruited, 82 patients (41 patella, 41 trochlea) were available for a clinical review at ≥10 years after surgery (mean follow-up, 11.9 years [range, 10-15 years]). For the whole patellofemoral MACI cohort, all PROMs significantly improved over time (P < .05), with no significant changes (P > .05) observed in any MRI-based score from 2 to ≥10 years after surgery. At ≥10 years, 90.2% (n = 74) were satisfied with MACI in relieving their knee pain, and 85.4% (n = 70) were satisfied with the improvement in their ability to participate in sports. No differences (P > .05) were observed in PROMs between those undergoing patellar MACI and those undergoing trochlear MACI, although a significant group effect was observed for limb symmetry indices of knee extensor (P = .009) and flexor (P = .041) strength, which were greater in those undergoing patellar (vs trochlear) MACI. No statistically significant differences (P > .05) were observed between patellar and trochlear grafts on any MRI-based measure. In the cohort assessed at ≥10 years after surgery, 4 patients (2 patella, 2 trochlea) demonstrated graft failure on MRI scans, although a further 3 patients (all trochlea) were omitted from the ≥10-year review for having already progressed to total knee arthroplasty. CONCLUSION: Good clinical scores, high levels of patient satisfaction, and adequate graft survivorship were observed at ≥10 years after MACI on the patella and trochlea.


Subject(s)
Chondrocytes , Patellofemoral Joint , Transplantation, Autologous , Humans , Patellofemoral Joint/surgery , Patellofemoral Joint/diagnostic imaging , Chondrocytes/transplantation , Adult , Female , Male , Follow-Up Studies , Prospective Studies , Young Adult , Patient Reported Outcome Measures , Middle Aged , Magnetic Resonance Imaging , Adolescent , Patella/surgery , Patella/diagnostic imaging , Patient Satisfaction , Treatment Outcome , Cartilage, Articular/surgery , Cartilage, Articular/injuries , Cartilage, Articular/diagnostic imaging
19.
J Child Fam Stud ; 33(3): 982-997, 2024 Mar.
Article in English | MEDLINE | ID: mdl-39184136

ABSTRACT

Despite custodial grandchildren's (CG) traumatic histories and risk for psychological difficulties, knowledge is scant regarding the frequencies, types, and consequences es of adverse childhood experiences (ACEs) they have encountered. We examined self-reported ACEs via online surveys with 342 CG (ages 12 to 18) who were recruited to participate in an RCT of a social intelligence training program. ACEs were assessed by 14 widely used items, and risk for internalizing (ID) and externalizing (ED) difficulties were measured using 80th percentile cut-offs on the Strengths and Difficulties Questionnaire. Classification and regression tree analyses included all 14 ACEs (along with CG gender and age) as predictors of ID and ED risk separately. Given possible comorbidity, analyses were run with and without the other risk type as a predictor. Less than 9% of CG self-reported no ACEs, 48.6% reported two to five ACEs, and 30.5 % reported ≥ 6. Irrespective of ED risk, bullying from peers strongly predicted ID risk. ED risk was peak among CG who also had risk for ID. Without ID risk as a predictor, ED risk was highest among CG who were emotionally abused, not lived with a substance abuser, and encountered neighborhood violence. The frequency and types of ACEs observed were alarmingly higher than those among the general population, suggesting that many CG have histories of trauma and household dysfunction. That a small number of ACEs among the 14 studied here were significant predictors of ID and ED risk challenges the widespread belief of a cumulative dose ACE effect.

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