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1.
JCO Precis Oncol ; 8: e2400161, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39013135

ABSTRACT

PURPOSE: To characterize the relationship between Decipher genomic classifier scores and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-based metastatic spread. MATERIALS AND METHODS: We identified patients from four institutions who underwent PSMA PET/CT scans pretreatment for primary staging or postradical prostatectomy (RP) for suspected recurrence and had Decipher transcriptomic data available from biopsy or RP specimens. PSMA PET/CT-based patterns of spread were classified as localized (miT + N0M0) or nonlocalized (miN1M0 or miM1a-c). We calculated the association between Decipher scores and the risk of nonlocalized disease on PSMA PET/CT using multivariable logistic regression for pretreatment patients and multivariable Cox regression for post-RP patients. We also compared select transcriptomic signatures between patients with localized and nonlocalized diseases. RESULTS: Five hundred eighty-six patients were included (pretreatment: n = 329; post-RP: n = 257). Higher Decipher scores were associated with nonlocalized disease on PSMA PET/CT both pretreatment (odds ratio, 1.18 [95% CI, 1.03 to 1.36] per 0.1 increase in Decipher score, P = .02) and post-RP (hazard ratio, 1.15 [95% CI, 1.05 to 1.27] per 0.1 increase in Decipher score, P = .003). In the pretreatment setting, nonlocalized disease was associated with higher rates of TP53 mutations and lower rates of PAM50 luminal A subtype compared with localized disease. In the post-RP setting, overexpression of signatures related to metabolism, DNA repair, and androgen receptor signaling were associated with higher rates of nonlocalized disease. CONCLUSION: Higher Decipher scores were associated with nonlocalized disease identified on PSMA PET/CT both pretreatment and post-RP. There were several transcriptomic differences between localized and nonlocalized diseases in both settings.


Subject(s)
Gene Expression Profiling , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms/genetics , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Retrospective Studies , Aged , Middle Aged , Glutamate Carboxypeptidase II/genetics , Antigens, Surface/genetics , Transcriptome
3.
Nat Chem Biol ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965384

ABSTRACT

Targeted protein degradation (TPD) is an emerging therapeutic strategy that would benefit from new chemical entities with which to recruit a wider variety of ubiquitin E3 ligases to target proteins for proteasomal degradation. Here we describe a TPD strategy involving the recruitment of FBXO22 to induce degradation of the histone methyltransferase and oncogene NSD2. UNC8732 facilitates FBXO22-mediated degradation of NSD2 in acute lymphoblastic leukemia cells harboring the NSD2 gain-of-function mutation p.E1099K, resulting in growth suppression, apoptosis and reversal of drug resistance. The primary amine of UNC8732 is metabolized to an aldehyde species, which engages C326 of FBXO22 to recruit the SCFFBXO22 Cullin complex. We further demonstrate that a previously reported alkyl amine-containing degrader targeting XIAP is similarly dependent on SCFFBXO22. Overall, we present a potent NSD2 degrader for the exploration of NSD2 disease phenotypes and a new FBXO22-recruitment strategy for TPD.

4.
Int J Cancer ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973574

ABSTRACT

The objective of this study is to report the long-term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event-free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre-specified groups. Two hundred and twenty-two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8-year EFS was 75% (95% confidence interval: 69%-83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow-up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post-chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.

5.
Eur Urol Oncol ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38987159

ABSTRACT

BACKGROUND AND OBJECTIVE: Renal function preservation is particularly important following nonoperative treatment of localized renal cell carcinoma (RCC) since patients are often older with medical comorbidities. Our objective was to report long-term renal function outcomes after stereotactic ablative radiotherapy (SABR) including patients with a solitary kidney. METHODS: Patients with primary RCC treated with SABR with ≥2 yr of follow-up at 12 International Radiosurgery Consortium for Kidney institutions were included. Renal function was measured by estimated glomerular filtration rate (eGFR). KEY FINDINGS AND LIMITATIONS: In total, 190 patients (56 with a solitary kidney) underwent SABR and were followed for a median of 5.0 yr (interquartile range [IQR]: 3.4-6.8). In patients with a solitary kidney versus bilateral kidneys, pre-SABR eGFR (mean [standard deviation]) was 61.1 (23.2) versus 58.0 (22.3) ml/min (p = 0.32) and the median tumor size was 3.65 cm (IQR: 2.59-4.50 cm) versus 4.00 cm (IQR: 3.00-5.00 cm; p = 0.026). At 5 yr after SABR, eGFR decreased by -14.5 (7.6) and -13.3 (15.9) ml/min (p = 0.67), respectively, and there were similar rates of post-SABR dialysis (3.6% [n = 2/56] vs 3.7% [n = 5/134]). A multivariable analysis demonstrated that increasing tumor size (odds ratio [OR] per 1 cm: 1.57; 95% confidence interval [CI]: 1.14-2.16, p = 0.0055) and baseline eGFR (OR per 10 ml/min: 1.30; 95% CI: 1.02-1.66, p = 0.034) were associated with an eGFR decline of ≥15 ml/min at 1 yr. CONCLUSIONS AND CLINICAL IMPLICATIONS: With long-term follow-up after SABR, kidney function decline remains moderate, with no observed difference between patients with a solitary kidney and bilateral kidneys. Tumor size and baseline eGFR are dominant factors predictive of long-term renal function decline. PATIENT SUMMARY: With long-term follow-up, stereotactic ablative radiotherapy (SABR) yields moderate long-term renal function decline and low dialysis rates even in patients with a solitary kidney. SABR thus represents a promising noninvasive, nephron-sparing option for patients with localized renal cell carcinoma.

6.
medRxiv ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38978658

ABSTRACT

Combining predictions from multiple models into an ensemble is a widely used practice across many fields with demonstrated performance benefits. The R package hubEnsembles provides a flexible framework for ensembling various types of predictions, including point estimates and probabilistic predictions. A range of common methods for generating ensembles are supported, including weighted averages, quantile averages, and linear pools. The hubEnsembles package fits within a broader framework of open-source software and data tools called the "hubverse", which facilitates the development and management of collaborative modelling exercises.

7.
Sci Rep ; 14(1): 15049, 2024 07 01.
Article in English | MEDLINE | ID: mdl-38951167

ABSTRACT

Vincristine (VCR) is one of the most widely used chemotherapy agents in treating pediatric cancer. Nonetheless, it is known to cause dose-dependent neurotoxicity which can impact virtually every organ system. Despite its widespread use, the precise impact of VCR on the lower urinary tract (LUT) remains inadequately elucidated. Our initial clinical and translational investigations suggest a sex-specific influence of childhood VCR exposure on LUT function. Thus, the current study aimed to investigate the late effects of systemic VCR exposure on LUT physiology and the underlying mechanisms, focusing on dosage and male-sex, employing juvenile CD-1 mice as a model. Male mice subjected to VCR exhibited augmented functional bladder capacity accompanied by frequent non-void contractions during awake cystometry, alongside mast cell accumulation within the bladder, compared to the saline-treated control group. Noteworthy functional changes were observed in bladder strips from the VCR group, including decreased nerve-mediated contraction, heightened contractile responses to cholinergic and purinergic agonists, enhanced responsiveness to histamine-primarily via histamine receptor 1 (Hrh1)-and an augmented relaxation effect with compound 48/80 (a mast cell degranulator), relative to the control group. Significant changes in gene expression levels associated with neuroinflammation and nociception were observed in both the bladder and lumbosacral dorsal root ganglia (Ls-DRG) of the VCR group. These findings suggest that VCR exposure during childhood, particularly in males, triggers neuroimmune responses in the bladder and Ls-DRG, amplifying responsiveness to neurotransmitters in the bladder, thereby contributing to LUT dysfunction characterized by a mixed bladder phenotype as a late effect during survivorship.


Subject(s)
Urinary Bladder , Vincristine , Animals , Male , Mice , Urinary Bladder/drug effects , Urinary Bladder/pathology , Female , Vincristine/adverse effects , Vincristine/pharmacology , Mast Cells/drug effects , Mast Cells/metabolism , Humans , Sex Factors , Dose-Response Relationship, Drug , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/pharmacology
8.
Eur Urol Oncol ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38972832

ABSTRACT

BACKGROUND AND OBJECTIVE: The extent of prostate cancer found on biopsy, as well as prostate cancer grade and genomic tests, can affect clinical decision-making. The impact of these factors on the initial management approach and subsequent patient outcomes for men with favorable-grade prostate cancer has not yet been determined on a population level. Our objective was to explore the association of Decipher 22-gene genomic classifier (GC) biopsy testing on the initial use of conservative management versus radical prostatectomy (RP) and to determine the independent effect of GC scores on RP pathologic outcomes. METHODS: A total of 87 140 patients diagnosed with grade group 1 and 2 prostate cancer between 2016 and 2018 from the Surveillance, Epidemiology, and End Results registry data were linked to GC testing results (2576 tested and 84 564 untested with a GC). The primary endpoints of interest were receipt of conservative management or RP, pathologic upgrading (pathologic grade group 3-5), upstaging (pathologic ≥T3b), and adverse pathologic features (pathologic upgrading, upstaging, or lymph node invasion). Multivariable logistic regressions quantified the association of variables with outcomes of interest. KEY FINDINGS AND LIMITATIONS: GC tested patients were more likely to have grade group 2 on biopsy (51% vs 46%, p < 0.001) and lower prostate-specific antigen (6.1 vs 6.3, p = 0.016). Conservative management increased from 37% to 39% and from 22% to 24% during 2016-2018 for the GC tested and untested populations, respectively. GC testing was significantly associated with increased odds of conservative management (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.9-2.4, p < 0.001). The distribution of biopsy GC risk was as follows: 45% low risk, 30% intermediate risk, and 25% high risk. In adjusted analyses, higher GC (per 0.1 increment) scores (OR 1.24, 95% CI 1.17-1.31, p < 0.001) and percent positive cores (1.07, 95% CI 1.02-1.12, p = 0.009) were significantly associated with the receipt of RP. A higher GC score was significantly associated with all adverse outcomes (pathologic upgrading [OR 1.29, 95% CI 1.12-1.49, p < 0.001], upstaging [OR 1.31, 95% CI 1.05-1.62, p = 0.020], and adverse pathology [OR 1.27, 95% CI 1.12-1.45, p < 0.001]). Limitations include observational biases associated with the retrospective study design. CONCLUSIONS AND CLINICAL IMPLICATIONS: Men who underwent GC testing were more likely to undergo conservative management. GC testing at biopsy is prognostic of adverse pathologic outcomes in a large population-based registry. PATIENT SUMMARY: In this population analysis of men with favorable-risk prostate cancer, those who underwent genomic testing at biopsy were more likely to undergo conservative management. Of men who initially underwent radical prostatectomy, higher genomic risk but not tumor volume was associated with adverse pathologic outcomes. The use of genomic testing at prostate biopsy improves risk stratification and may better inform treatment decisions than the use of tumor volume alone.

9.
Cell Rep ; 43(8): 114510, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39018246

ABSTRACT

Ubiquitination is an essential regulator of cell division. The kinase Polo-like kinase 1 (PLK1) promotes protein degradation at G2/M phase through the E3 ubiquitin ligase Skp1-Cul1-F box (SCF)ßTrCP. However, the magnitude to which PLK1 shapes the mitotic proteome is uncharacterized. Combining quantitative proteomics with pharmacologic PLK1 inhibition revealed a widespread, PLK1-dependent program of protein breakdown at G2/M. We validated many PLK1-regulated proteins, including substrates of the cell-cycle E3 SCFCyclin F, demonstrating that PLK1 promotes proteolysis through at least two distinct E3 ligases. We show that the protein-kinase-A-anchoring protein A-kinase anchor protein 2 (AKAP2) is cell-cycle regulated and that its mitotic degradation is dependent on the PLK1/ßTrCP signaling axis. Expression of a non-degradable AKAP2 mutant resulted in actin defects and aberrant mitotic spindles, suggesting that AKAP2 degradation coordinates cytoskeletal organization during mitosis. These findings uncover PLK1's far-reaching role in shaping the mitotic proteome post-translationally and have potential implications in malignancies where PLK1 is upregulated.

10.
Mol Psychiatry ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009701

ABSTRACT

Dyslexia is a learning difficulty with neurodevelopmental origins, manifesting as reduced accuracy and speed in reading and spelling. It is substantially heritable and frequently co-occurs with other neurodevelopmental conditions, particularly attention deficit-hyperactivity disorder (ADHD). Here, we investigate the genetic structure underlying dyslexia and a range of psychiatric traits using results from genome-wide association studies of dyslexia, ADHD, autism, anorexia nervosa, anxiety, bipolar disorder, major depressive disorder, obsessive compulsive disorder, schizophrenia, and Tourette syndrome. Genomic Structural Equation Modelling (GenomicSEM) showed heightened support for a model consisting of five correlated latent genomic factors described as: F1) compulsive disorders (including obsessive-compulsive disorder, anorexia nervosa, Tourette syndrome), F2) psychotic disorders (including bipolar disorder, schizophrenia), F3) internalising disorders (including anxiety disorder, major depressive disorder), F4) neurodevelopmental traits (including autism, ADHD), and F5) attention and learning difficulties (including ADHD, dyslexia). ADHD loaded more strongly on the attention and learning difficulties latent factor (F5) than on the neurodevelopmental traits latent factor (F4). The attention and learning difficulties latent factor (F5) was positively correlated with internalising disorders (.40), neurodevelopmental traits (.25) and psychotic disorders (.17) latent factors, and negatively correlated with the compulsive disorders (-.16) latent factor. These factor correlations are mirrored in genetic correlations observed between the attention and learning difficulties latent factor and other cognitive, psychological and wellbeing traits. We further investigated genetic variants underlying both dyslexia and ADHD, which implicated 49 loci (40 not previously found in GWAS of the individual traits) mapping to 174 genes (121 not found in GWAS of individual traits) as potential pleiotropic variants. Our study confirms the increased genetic relation between dyslexia and ADHD versus other psychiatric traits and uncovers novel pleiotropic variants affecting both traits. In future, analyses including additional co-occurring traits such as dyscalculia and dyspraxia will allow a clearer definition of the attention and learning difficulties latent factor, yielding further insights into factor structure and pleiotropic effects.

11.
Elife ; 132024 Jul 19.
Article in English | MEDLINE | ID: mdl-39027985

ABSTRACT

How is new information organized in memory? According to latent state theories, this is determined by the level of surprise, or prediction error, generated by the new information: a small prediction error leads to the updating of existing memory, large prediction error leads to encoding of a new memory. We tested this idea using a protocol in which rats were first conditioned to fear a stimulus paired with shock. The stimulus was then gradually extinguished by progressively reducing the shock intensity until the stimulus was presented alone. Consistent with latent state theories, this gradual extinction protocol (small prediction errors) was better than standard extinction (large prediction errors) in producing long-term suppression of fear responses, and the benefit of gradual extinction was due to updating of the conditioning memory with information about extinction. Thus, prediction error determines how new information is organized in memory, and latent state theories adequately describe the ways in which this occurs.


Subject(s)
Brain , Fear , Memory , Animals , Rats , Memory/physiology , Fear/physiology , Brain/physiology , Male , Extinction, Psychological/physiology , Conditioning, Classical/physiology
13.
J Strength Cond Res ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38968202

ABSTRACT

ABSTRACT: Dengel, DR, Studee, HR, Juckett, WT, Bosch, TA, Carbuhn, AF, Stanforth, PR, and Evanoff, NG. Muscle-to-bone ratio in NCAA division I collegiate football players by position. J Strength Cond Res XX(X): 000-000, 2024-The purpose of this study was to compare the muscle-to-bone ratio (MBR) in National Collegiate Athletic Association Division I football players (collegiate football players [CFP]) to healthy, age-matched controls. In addition, we examined MBR in CFP by position. A total of 553 CFP and 261 controls had their total and regional lean mass (LM), fat mass (FM), and bone mineral content (BMC) determined by dual x-ray absorptiometry (DXA). College football players were categorized by positions defined as offensive linemen (OL), defensive linemen (DL), tight end, linebacker (LB), running back (RB), punter or kicker, quarterback (QB), defensive back (DB), and wide receiver (WR). There were significant differences between CFP and controls for total LM (80.1 ± 10.0 vs. 56.9 ± 7.8 kg), FM (22.2 ± 12.5 vs. 15.2 ± 7.1 kg), and BMC (4.3 ± 0.5 vs. 3.1 ± 0.5 kg). Although there were significant differences in body composition between CFP and controls, there was no significant differences in total MBR between CFP and controls (18.6 ± 1.4 vs. 18.8 ± 1.7). Regionally, CFP had significantly lower trunk MBR than controls (26.7 ± 2.7 vs. 28.7 ± 4.2), but no difference was seen in leg or arm MBR. Positional differences in CFP were noted as total MBR being significantly higher in DL (19.0 ± 1.4) than in DB (18.1 ± 1.3), WR (18.1 ± 1.3), and LB (18.2 ± 1.3). OL had a significantly higher total MBR (19.2 ± 1.3) than DB (18.1 ± 1.3), LB (18.2 ± 1.3), QB (18.1 ± 1.0), and WR (18.1 ± 1.3). In addition, RB had significantly higher total MBR (18.8 ± 1.3) than DB (18.1 ± 1.3) and WR (18.1 ± 1.3). This study may provide athletes and training staff with normative values when evaluating total and regional MBR with DXA.

14.
Pract Radiat Oncol ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39019209

ABSTRACT

Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiotherapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of an expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by three cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques like MRI-guided SBRT, and SBRT response assessment.

15.
Chem Commun (Camb) ; 60(59): 7582-7585, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38962853

ABSTRACT

A porous three-component hydrogen bonded framework, 1⋅biphen⋅TP, was prepared from a tetra-amidinium component (14+) and two different dianions, benzene-1,4-dicarboxylate (terephthalate, TP2-) and biphenyl-4,4'-dicarboxylate (biphen2-). Interestingly, when the framework was prepared in ethanol/water, 1⋅biphen⋅TP forms even when an excess of either dicarboxylate is present. However, when only water is used as solvent, only two-component frameworks are formed.

16.
Nat Med ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844796

ABSTRACT

Recent research showed that precision medicine can identify new treatment strategies for patients with childhood cancers. However, it is unclear which patients will benefit most from precision-guided treatment (PGT). Here we report consecutive data from 384 patients with high-risk pediatric cancer (with an expected cure rate of less than 30%) who had at least 18 months of follow-up on the ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial. A total of 256 (67%) patients received PGT recommendations and 110 (29%) received a recommended treatment. PGT resulted in a 36% objective response rate and improved 2-year progression-free survival compared with standard of care (26% versus 12%; P = 0.049) or targeted agents not guided by molecular findings (26% versus 5.2%; P = 0.003). PGT based on tier 1 evidence, PGT targeting fusions or commenced before disease progression had the greatest clinical benefit. Our data show that PGT informed by comprehensive molecular profiling significantly improves outcomes for children with high-risk cancers. ClinicalTrials.gov registration: NCT03336931.

17.
Urol Oncol ; 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38853055

ABSTRACT

Recognizing sexual orientation and gender identity (SOGI) is paramount in the management of genitourinary cancers, as sexual and gender minority (SGM) individuals encounter unique healthcare challenges leading to disparities. SGM patients often confront systemic barriers, provider biases, and scarcity of tailored resources, resulting in diminished satisfaction and adverse health outcomes. The evaluation and treatment of genitourinary cancers in SGM patients demand a nuanced, multidisciplinary approach that focuses on the unique health determinants often overlooked by the healthcare system. This review highlights recommendations for the inclusivity of SGM patients within the clinic, from inclusive signage to gender inclusive language. For the evaluation and treatment of SGM patients with genitourinary cancers, it is recommended to employ organ-based language, to utilize validated questionnaires encompassing mental health, sexual behavior, and patient-reported outcomes, and to provide timely referrals to social work and onco-fertility when appropriate. Ultimately, approaching inclusivity through education targeted at both SGM patients and healthcare providers is pivotal for centering care around the patient, improving the quality of life and outcomes for SGM patients facing genitourinary cancers.

18.
Coron Artery Dis ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38861193

ABSTRACT

BACKGROUND: Despite innovations in pharmacotherapy to lower lipoprotein cholesterol and apolipoprotein B, risk factors for atherosclerotic cardiovascular disease (ASCVD), ASCVD persists as the leading global cause of mortality. Elevations in low-density lipoprotein cholesterol (LDL-C) are a well-known risk factor and have been a main target in the treatment of ASCVD. The latest research suggests that ketogenic diets are effective at improving most non-LDL-C/apolipoprotein B cardiometabolic risk factors. However, ketogenic diets can induce large increases in LDL-C to >190 mg/dl in some individuals. Interestingly, these individuals are often otherwise lean and healthy. The influence of increased levels of LDL-C resulting from a carbohydrate-restricted ketogenic diet on the progression of atherosclerosis in otherwise metabolically healthy individuals is poorly understood. This observational study aims to assess and describe the progression of coronary atherosclerosis in this population within 12 months. METHODS: Hundred relatively lean individuals who adopted ketogenic diets and subsequently exhibited hypercholesterolemia with LDL-C to >190 mg/dl, in association with otherwise good metabolic health markers, were enrolled and observed over a period of 12 months. Participants underwent serial coronary computed tomography angiography scans to assess the progression of coronary atherosclerosis in a year. RESULTS: Data analysis shall begin following the conclusion of the trial with results to follow. CONCLUSION: Ketogenic diets have generated debate and raised concerns within the medical community, especially in the subset exhibiting immense elevations in LDL-C, who interestingly are lean and healthy. The relationship between elevated LDL-C and ASCVD progression in this population will provide better insight into the effects of diet-induced hypercholesterolemia.

19.
Am Surg ; : 31348241259033, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38867656

ABSTRACT

BACKGROUND: Multimodal pain management has been shown to be effective in treating pain in acutely injured trauma patients. Our community-based, level 1 trauma center previously published in 2022 the efficacy of implementing multimodal pain control (MMPC) protocol in our inpatient trauma population which decreased the use of opioids while maintaining similar pain control. The MMPC group had a trend toward higher age and was significantly less injured. We hypothesize MMPC will reduce opioid consumption in both the advanced aged and more severely injured trauma populations while still providing adequate pain control. METHODS: Defined by the year of admission, MMPC and physician managed pain control (PMPC) were compared in both advanced age groups and between the severely injured groups. The advanced age group included patients ≥55 years old. The severely injured group included ≥18 years old with ≥15 ISS. Primary outcomes were total opioid utilization per day, calculated in morphine milliequivalents (MME), and median daily pain scores. RESULTS: For the severely injured population, the MMPC group showed a 3-fold decrease in opioid use (30 MME/d vs 90.3 MME/d, P < .001) and lower pain scores (5/10 vs 6/10, P < .001) than the PMPC group. In the advance age group, there was no significant difference between MMPC and PMPC groups in opioid use (P = .974) or pain scores (P = .553). CONCLUSION: MMPC effectively reduces opioid consumption in a severely injured patient population while simultaneously improving pain control. Advanced age trauma patients can require complex pain management solutions and future research to determine their needs is recommended.

20.
J Arthroplasty ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38914143

ABSTRACT

BACKGROUND: Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty (TKA) for localized osteoarthritis. Recent advancements in UKA implant design and expanding patient criteria may have increased its utilization. However, few studies have examined the use of UKA in the United States. Thus, this study assessed the current and projected future trends of UKA and robotic UKA in the United States through 2035, along with postoperative outcomes. METHODS: A collaborative healthcare research network was queried to identify patients who had undergone UKA. Primary outcomes measured included prevalence (P), incidence proportion (IP), and incidence rate (IR) from 2012 to 2022. Chi-squared analyses were done to compare outcomes across categorical data. Regression modeling was performed to project UKA to the year 2035. Statistical significance was held at P < .05 for all analyses. RESULTS: In 2022, 1,662 UKAs were performed within the network, a 590% increase from 2012 (241 performed). The IP increased on an average annual basis by 41.8%, the IR by 50%, and the P by 51.3%. A year following UKA, conversion to TKA was the most common orthopaedic complication (39.9%). As of 2022, there were 68 robotic UKAs performed, a 518% increase from the 11 performed in 2012. Regression analysis for UKA through 2035 showed that IP will be 0.04%, IR will be 1.75 × 10-6 cases/person-day, and P will be 0.3%. CONCLUSIONS: These findings are consistent with prior studies indicating a higher utilization of UKA over the past decade. Reported complications were not uncommon, as nearly 40% of patients required a conversion to a TKA. Further research is needed to optimally identify criteria for appropriate patients and determine the benefits robotic UKA may provide, specifically reducing the risk of conversion to a TKA.

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