University of Oklahoma Health Sciences Center

Background Invasive fusariosis is rarely reported post-chimeric antigen receptor T-cell (CAR-T) therapy. We herein present a case of cutaneous invasive Fusarium infection and provide a compilation of similar cases documented in the existing literature. Case Summary A 61-year-old woman with relapsed refractory diffuse large B-cell lymphoma and secondary hemophagocytic lymphohistiocytosis received CD19-CAR-T therapy. She developed grade 1 cytokine release syndrome (CRS) and grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), requiring dexamethasone and anakinra. Twenty-five days after CAR-T, she developed bilateral proximal thigh nodular lesions. Skin biopsy revealed hyphal structures with hyphal structures, and culture revealed Fusarium species. Treatment with liposomal amphotericin B, voriconazole, and terbinafine followed by voriconazole and terbinafine led to clinical improvement. Conclusion Though rare, healthcare providers should maintain an index of suspicion for Fusarium infections in recipients of cellular therapies with risk factors.

To evaluate the effects of a very-low-calorie diet (VLCD) on insulin resistance (IR), metabolic gene expression, and fatty acid profiles in obese patients (body mass index [BMI] ≥ 30 kg/m2) undergoing bariatric surgery compared to age- and sex-matched nonobese controls (BMI ≤ 25 kg/m2) undergoing elective abdominal surgery. A total of 38 participants (21 obese and 17 nonobese controls) were recruited for this study. Obese patients underwent VLCD (800 kcal/day) for four weeks before surgery. Fasting blood samples and tissue biopsies were collected during surgery. Key parameters included IR (measured using HOMA-IR), metabolic gene expression (quantified via RT-PCR), and fatty acid composition (analyzed by gas chromatography). Data were compared between pre- and post-VLCD groups in the obese cohort. GLUT4 expression was reduced (1.57-fold, p = 0.025), whereas PDK4 (3.9-fold, p = 0.002), CPT1 (2.5-fold, p = 0.013), and AMPK (twofold, p = 0.004) expression were Correlation analysis revealed that GLUT4 was negatively correlated with BMI (r = -0.85), glucose (r = -0.94), and IR (r = -0.79), CPT1 was positively correlated with these parameters (BMI: r = 0.84, glucose: r = 0.92, IR: r = 0.82). VLCD significantly reduced monounsaturated fatty acids, including alpha-linolenic acid (p = 0.03) and erucic acid (p = 0.019). Postsurgical improvements included reductions in BMI (Δ = 6.21, p < 0.0001), glucose level (Δ = 6.94, p = 0.0007), and IR (Δ = 10.19, p = 0.0039). VLCD modulated metabolic gene expression and fatty acid profiles, enhancing IR and metabolic health both pre- and post-surgery. This represents a critical strategy for optimizing the outcomes of obese patients undergoing bariatric surgery.

Timely initiation of treatment is a core principle of oncologic care, especially for aggressive cancers such as lung cancer. However, the real-world impact of short-term delays in treatment initiation on survival outcomes in lung cancer remains unclear. This meta-analysis evaluates the association between treatment delays of 4, 8, and 12 weeks and all-cause mortality in lung cancer patients. A systematic search was conducted in PubMed, Scopus, and Web of Science for studies published between 2000 and 2025. Of 5360 screened records, 15 studies were included, comprising 16 cohorts for overall survival of lung cancer patients. Hazard ratios (HRs) for 4-, 8-, and 12-week treatment delays were estimated using random-effects meta-analyses. Heterogeneity was measured with the I ² statistic, and publication bias was assessed using funnel plots and Egger’s test. No significant association was found between treatment delay and survival at any of the time points. Pooled HRs were 1.00 (95% CI, 0.99–1.02) for a 4-week delay, 1.01 (95% CI, 0.99–1.03) for an 8-week delay, and 1.01 (95% CI, 0.98–1.05) for a 12-week delay. Despite high heterogeneity ( I ² = 97%), no evidence of publication bias was detected. This meta-analysis found no significant impact of short-term treatment delays (up to 12 weeks) on mortality in lung cancer patients. These findings challenge the assumption that brief delays universally worsen outcomes and underscore the importance of individualized treatment planning and prioritization.

The field of targeted therapy exploits the selective expression of therapeutic genes or proteins in diseased cells. While this area is gaining attraction in the context of cardiovascular diseases, diabetes, and other major health disorders, it has been most extensively explored in the realm of cancer. Targeted therapy has gained significance in the cancer field for its potential to address the limitations of conventional treatments and enhance patient survival. Interleukin‐24 (IL‐24), a versatile cytokine, has been evaluated as a cancer therapeutic in various preclinical cancer models and clinical trials, and has yielded promising results. Consequently, multiple studies highlight IL‐24 as a viable “anti‐cancer” therapeutic, with successful outcomes observed in combination therapies involving small molecule inhibitors, chemotherapeutic drugs, and radiation. Despite the evidence validating the tumor‐suppressing properties of IL‐24 in cancer models, there is a dearth of information regarding its role in other human diseases. The objective of this review is to offer a synopsis of the potential role of IL‐24 in diverse human diseases. Additionally, it provides a comprehensive review of the progress in cancer therapy utilizing IL‐24. Finally, from the author's standpoint, the review also addresses some of the limitations that impede the translational potential of IL‐24‐based therapy in clinical settings. It offers arguments in favor of incorporating IL‐24‐based targeted therapy as an effective and safer alternative for current treatment modalities, thereby highlighting its potential to revolutionize the field of therapeutics.

Objective To evaluate the efficacy and cytotoxicity of in‐office bleaching gels with hyaluronic acid (HA) or carbomer 940 (CAR), titanium dioxide nanoparticles co‐doped with nitrogen and fluorine (NF_TiO 2 ), and hydrogen peroxide (HP; H 2 O 2 ) at 1.5% and 6% with violet LED irradiation. Materials and Methods 48 bovine enamel/dentin discs (5 × 3 mm) stained with black tea for 24 h were assigned to six groups ( n = 8): HA‐1.5%HP + LED, HA‐6%HP + LED, CAR‐1.5%HP + LED, CAR‐6%HP + LED, 35%HP‐commercial (control), and a negative control (no treatment). The discs were placed in artificial pulp chambers (APCs) and underwent three 30‐min bleaching sessions with 20 violet LED cycles (1‐min activation, 30‐s pause) at 7‐day intervals. Extracts were applied to MDPC‐23 cells, assessing color change (ΔE 00 ), whiteness index (ΔWI D ), H 2 O 2 diffusion, cell viability (CV), oxidative stress (OxS), and cell morphology (SEM). Data were analyzed by one‐way ANOVA and Tukey post hoc test ( α = 0.05). Results Gels with HA showed no statistical difference in ΔE 00 and ΔWI D compared with 35%HP‐commercial ( p > 0.05). H 2 O 2 diffusion and oxidative stress were lower in 1.5% and 6% HP groups. Cell viability was higher in 1.5% HP groups ( p < 0.05). There were no changes in cell morphology. Conclusion Bleaching gels with HA, NF_TiO 2 NPs, low H 2 O 2 concentrations, and violet LED irradiation reduced cytotoxicity without compromising efficacy. Clinical Relevance Experimental bleaching gels with hyaluronic acid, NF_TiO 2 nanoparticles, low H 2 O 2 concentrations, and combined with violet LED irradiation achieve similar efficacy to high‐H 2 O 2 gels (35%). This approach also promises to reduce cytotoxic damage, providing a safer in‐office bleaching option.

Background ZYN is the leading nicotine pouch brand and a predominant driver of nicotine pouch advertising. In November 2022, Philip Morris International (PMI) acquired Swedish Match, the manufacturer of ZYN. Methods We conducted a content analysis of 207 US-based consumer-facing ZYN advertisements (ads) from January 2019 to June 2023 to delineate the characteristics of ZYN ads and compare them before and after Swedish Match was acquired by PMI. Results Most ZYN ads were on digital media, and nearly all included information on nicotine strength and flavour. Peppermint was the most advertised flavour across time. After the acquisition, ZYN ads included significantly fewer ‘tobacco-free’ claims, whereas ‘spit-free’ claims significantly increased. The most common marketing claims were that multiple choices of products were available, followed by easy to buy, change, sales success, ability to use anywhere and improved social interaction before and after the acquisition. The percentages of ads with easy to buy, change and sales success claims, reward programmes and those linked to websites significantly increased after the acquisition. Conclusions After PMI acquired Swedish Match, ZYN ads used ‘tobacco-free’ claims less frequently. The most advertised marketing claims remained unchanged but were made more frequently in post-acquisition ads. Such claims, together with the promotion of reward programmes and links to websites for easy purchase, may attract young people or those who do not use tobacco to ZYN, indicating a need for increased monitoring and potential restrictions.

Given their rarity and diversity, a fundamental understanding of the genomic underpinnings for many sarcoma subtypes is still lacking. To better define the molecular landscape of this group of diseases, we perform matched whole exome sequencing and RNA sequencing on a cohort of 1340 sarcoma tumor specimens. We identify recurrent somatic mutations and observe an increased mutational burden in metastatic vs. primary samples (p < 0.001). We observe frequent copy number alterations including whole genome doubling, with this feature being more common in metastatic tumors (p = 0.026). Estimation of immune cell abundances followed by hierarchical clustering identifies five immune subtypes ranging from low to high and we observe inferior overall survival in immune deplete clusters compared to immune enriched (p < 0.01). Interestingly, GIST predominantly form a distinct “immune intermediate” cluster that is marked by a specific enrichment for NK cells (FDR < 0.01).

BACKGROUND: It remains unclear whether there is a difference in overall survival (OS) benefit between (m)FOLFIRINOX and gemcitabine-nab-paclitaxel as preoperative regimens for localised pancreatic adenocarcinoma. This study aimed to investigate the outcome of patients with resected localised pancreatic adenocarcinoma following (m)FOLFIRINOX versus gemcitabine-nab-paclitaxel. METHODS: International multicentre retrospective study (16 centres, 8 countries, 3 continents), including consecutive patients after pancreatic resection for localised pancreatic adenocarcinoma following 2-6 months preoperative (m)FOLFIRINOX or gemcitabine-nab-paclitaxel (2010-2018). Primary endpoint was OS from start of preoperative chemotherapy. Cox regression analysis was performed to investigate the association of the preoperative chemotherapy regimen with OS, adjusted for confounders at diagnosis. RESULTS: Overall, 935 patients were included after resection of localised pancreatic adenocarcinoma following preoperative (m) FOLFIRINOX (65%) or gemcitabine-nab-paclitaxel (35%). Preoperative chemotherapy regimen (m)FOLFIRINOX was not associated with OS (HR = 0.83 [95% CI 0.64-1.08]), compared to gemcitabine-nab-paclitaxel. Interaction analysis showed stronger effect of (m) FOLFIRINOX in patients with a lower (i.e., non-elevated/marginally elevated) serum CA19-9 at diagnosis (p interaction = 0.032). CONCLUSION: This international study found no OS benefit of preoperative (m)FOLFIRINOX in patients with resected localised pancreatic adenocarcinoma compared to gemcitabine-nab-paclitaxel.

Knowledge regarding in-the-moment antecedents of cannabis use is lacking. We examined internal (e.g., mood, cravings) and external (e.g., locations, people) antecedents of cannabis use among young adults regularly using both cannabis and tobacco. Over 30 days, 36 young adults (Mage = 24.2 years, 33% female, 8% nonbinary, 61% sexual minority, 44% Non-Hispanic White) completed multiple daily Ecological Momentary Assessment surveys, totaling 1,632 prompts. Generalized estimating equations estimated population-averaged relationships between the presence of antecedents and cannabis use outcomes (use vs. nonuse). Overall cannabis use was likelier at neutral ranges of affect (aOR = 0.95; 95% CI [0.91, 1.00]) and affective arousal (aOR = 1.52; 95% CI [0.91, 1.00], see Footnote 1), higher cannabis craving (aOR = 1.52; 95% CI [1.31, 1.76]), and substance intoxication (aOR = 1.25; 95% CI [1.01, 1.55]). Overall use was likelier at home (aOR = 1.97; 95% CI [1.16, 3.37]), and less likely in a place where cannabis smoking was forbidden (aOR = 0.46; 95% CI [0.25, 0.85]) or more people were present (aOR = 0.91; 95% CI [0.87, 0.96]). Other antecedents of use were seeing cannabis product packaging (aOR = 1.91; 95% CI [1.07, 3.39]) and experiencing racial/ethnic-based discrimination (aOR = 2.26; 95% CI [1.39, 3.69]). Future digital interventions for cannabis use will benefit from (a) testing real-time interactions between internal and external antecedents and (b) triggering interventions while users are at home alone, after discrimination experiences, and/or when feeling mild, neutral affect. Note: CIs containing 1.00 interpreted as statistically significant are due to having rounded up to the upper limit.

Background Population‐level adverse effects of obesity beyond commonly considered chronic conditions need to be characterized to understand its overall burden. Objective To assess the cross‐sectional associations between obesity and self‐reported status of overall health, quality of life, pain, fatigue, ability of physical activity, and the risks of developing chronic pain syndrome, chronic fatigue syndrome, fibromyalgia, and insomnia. Methods Using data from the All of Us Research Program (the United States), we included participants with a body mass index (BMI) ≥18.5 kg/m ² and available Overall Health Survey or electronic health records. Cross‐sectional analyses of self‐reported variables were conducted using multivariable logistic and linear regression models. Cox proportional‐hazard models were used to assess risks for incident outcomes. Results Among 323,640 participants (60.3% were female, mean age: 51.3 years), 20.7%, 11.0%, and 9.5% were with Classes I, II, and III obesity, respectively. Higher BMI categories were correlated with worse health metrics, with Class III obesity exhibiting the greatest disparities. Among those with Class III obesity, 9.6% (vs. 3.2% for normal weight) reported poor overall health, 28.3% (vs. 13.2%) reported severe pain, and 11.8% (vs. 8.4%) had prevalent insomnia. Graded associations were observed across high BMI categories, with Class III obesity showing the strongest effects. Compared with normal weight, in Class III obesity, the odds ratio (95% CI) was 3.82 (3.69–3.96) for fair/poor overall health, 3.93 (3.71–4.17) for severe pain, and 3.13 (2.98–3.29) for severely limited physical activity; the hazard ratio (95% CI) was 2.83 (2.36–3.40) for fibromyalgia and 1.53 (1.41–1.65) for insomnia. Conclusion Obesity imposes a substantial burden on broad aspects of well‐being in the US population.

Introduction Current literature addressing fetal cannabis exposure and neonatal outcomes is based on subjective measures with varying levels of significance. This systematic review and meta-analysis determined if neonates with fetal cannabis exposure have an increased odds of being born small for gestational age, low birth weight, admitted to the Neonatal Intensive Care Unit (NICU) immediately after delivery, and/or preterm. Methods To identify relevant articles, we searched five databases using standard search criteria. Two authors used the Newcastle–Ottawa Scale to exclude articles with a high risk of bias. To estimate the combined effect, we calculated pooled odd ratios (OR) with 95% confidence intervals (CI) using the Mantel–Haenszel method for dichotomous data. Results Of 3,390 original articles we identified through the search strategy, 13 met the inclusion criteria. This meta-analysis indicates that neonates with fetal cannabis exposure have higher odds of being small for gestational age (OR = 1.79; 95% CI = 1.24–2.59) and/or having a low birth weight (OR = 1.38; 95% CI = 1.05–1.89) compared to neonates without fetal cannabis exposure. The results regarding NICU admission and preterm birth were statistically inconclusive (NICU admission: OR = 1.38, 95% CI = 0.86–2.22; Preterm birth: OR = 1.29, 95% CI = 0.97–1.71). Although the odds ratios for these associations span one suggesting a null relationship, they have an upper bound that may be clinically relevant. Discussion Based on these findings, further research, as well as an evaluation of the current public health response, is warranted. Additional research is needed to identify the association between neonatal outcomes and specific nuances of fetal cannabis exposure, such as route of ingestion, frequency of use, dose consumed, and the timing of intrauterine exposure.

Introduction Patients with cancer have limited access to comprehensive pain treatment. We developed a 90‐min, single‐session, telehealth, interdisciplinary intervention that combines cancer‐specific medical education and behavioral pain treatment. We evaluated the intervention's preliminary feasibility and acceptability for patients with cancer‐related pain. Methods Adults with cancer‐related pain (≥ 4/10, average pain) who are receiving cancer treatment (< 3 months) self‐enrolled or were recruited from the Stephenson Cancer Center (SCC) in Oklahoma. Patients completed a baseline survey and attended the 90‐min group‐based, Zoom‐delivered telehealth intervention. They completed post‐intervention, 2‐week, and 4‐week follow‐up assessments and an optional debriefing interview. The feasibility benchmark was ≥ 70% attendance and 80% of acceptability items rated ≥ 4/5. Results Seventy participants (67.5% female; mean age = 52.5 years; 25% rural‐dwelling) enrolled. Forty of 70 (57%) attended the intervention. Of those, 95% completed the post‐intervention survey, and 90% and 95% completed the 2‐week and 4‐week follow‐ups, respectively. Participants reported high acceptability, understandability (97%), and relevance (90%). Most (80%) would recommend the class to others. Qualitative feedback highlighted reduced helplessness and fear regarding opioid use, adoption of behavioral pain management strategies, and appreciation for the convenience of telehealth. Exploratory analyses showed significant reductions in pain intensity (mean difference [MD] = 1.27, p = 0.001), pain interference (MD = 5.48, p = 0.017), pain catastrophizing (MD = 6.0, p = 0.003), sleep disturbance (MD = 3.64, p = 0.004), and depression (MD = 3.97, p = 0.018) at 4 weeks. Conclusion While attendance was below feasibility benchmarks, this interdisciplinary, telehealth intervention was acceptable and improved self‐reported cancer pain management. Further research will identify barriers to improve attendance, and determine the optimal timing within the cancer trajectory to deliver pain self‐management content. Randomized controlled trials are needed to assess intervention efficacy on patient outcomes.

Depression is a prevalent but often underrecognized comorbidity among cancer patients. Emerging evidence suggests that psychological distress may adversely impact cancer outcomes, but the magnitude of its effect on survival remains unclear. This meta-analysis evaluates the association between depression diagnosed after cancer diagnosis and cancer-specific and all-cause mortality across major cancer types. A systematic search of PubMed, Web of Science, Google Scholar, and the Cochrane Library was conducted to identify cohort studies examining the impact of depression on cancer mortality. Studies were included if they assessed clinically diagnosed depression or depressive symptoms using validated scales and reported hazard ratios (HRs) for mortality outcomes. A random-effects meta-analysis was performed to pool HR estimates, with heterogeneity assessed via Cochran’s Q and I ² statistics. Funnel plots and Egger’s test were used to evaluate publication bias. A total of 65 cohort studies were included. Depression was associated with significantly increased cancer-specific mortality in colorectal cancer (HR 1.83, 95% CI 1.47–2.28), breast cancer (HR 1.23, 95% CI 1.13–1.34), lung cancer (HR 1.59, 95% CI 1.36–1.86), and prostate cancer (HR 1.74, 95% CI 1.36–2.23). When considering mixed cancer types, depression was linked to a 38% increased risk of cancer mortality (HR 1.38, 95% CI 1.20–1.60). Significant heterogeneity was observed across studies ( I ² range 56–98%), suggesting variations in study populations and methodologies. Sensitivity analyses confirmed the robustness of the findings, and trial sequential analysis indicated sufficient evidence for a conclusive association. Depression after cancer diagnosis is associated with a significantly increased risk of cancer-specific mortality across multiple cancer types. These findings highlight the urgent need for integrating routine mental health screening and interventions into oncology care. Future research should focus on mechanistic pathways and targeted interventions to mitigate the negative impact of depression on cancer survival.

Background Preliminary phase I clinical trial results revealed that autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) preserved right ventricular cardiac function. To establish the efficacy of intramyocardial injections of an autologous UCB-MNC product at the time of stage II palliation surgery in patients with hypoplastic left heart syndrome (HLHS). Methods A phase IIb, multicenter, open-label, nonrandomized study was conducted. Ninety-five children (fifty treated and forty-five controls) with HLHS and its variants, a history of stage I palliation surgery, and planned stage II palliation surgery at less than thirteen months were enrolled. We assessed coprimary efficacy endpoints for changes in right ventricular cardiac function through fractional area changes and longitudinal and circumferential strain, both in the short term (three months) and long term (twelve months). Second, we assessed changes in biomarkers of cardiac injury. Safety endpoints included severe adverse events (SAEs), changes in overall health through vital signs, and cumulative hospitalization. Results Assessment of our coprimary efficacy endpoints revealed an unfavorable change in longitudinal cardiac strain in the treatment group compared with an improvement in strain in the control group (unadjusted p =.032) in the short term. No differences were observed between the groups in terms of other coprimary efficacy endpoints in the short or long term. A secondary assessment of biomarkers of cardiac injury revealed higher troponin T levels in the treatment group at three and six hours postsurgery. Regarding safety, no deaths related to the administered product or delivery procedure were reported. The treatment group presented a greater incidence (20%) of at least one SAE than the control group at three months (p =.048). Additionally, no statistically significant differences were found for the other safety endpoints. Conclusion Intramyocardial injections of autologous UCB-MNC products into the right ventricular myocardium during stage II palliation surgery failed to enhance cardiac function in patients with hypoplastic left heart syndrome. Registered on ClinicalTrials.gov Registered on ClinicalTrials.gov (NCT03779711) on 12/04/2018; URL: https://clinicaltrials.gov/ct2/show/NCT0377971.