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AbstractBackgroundFractional carbon dioxide (CO2) laser resurfacing is used successfully for facial rejuvenation. Post procedure skincare is a variable that influences downtime caused by pain/tenderness, erythema, crusting, and bruising.AimsThe primary objective of this pilot study was to demonstrate the benefits of human platelet extract (HPE) (plated)™ CALM Serum, a new topical cosmetic product, following fractionated CO2 ablative laser resurfacing treatment to the entire face versus standard of care.MethodsIn a single‐center, randomized, evaluator‐blinded pilot study, a total of 18 subjects were randomized into two groups, CO2 facial resurfacing followed by post‐procedural standard of care (Stratacel silicone gel) or CO2 facial resurfacing with the addition of HPE renewosomes in the CALM Serum.ResultsCALM Serum demonstrated statistically significant less crusting at Day 10 compared to the control group (p = 0.0193) with less downtime in the first 14 days (p = 0.03). Subjects treated with CALM Serum had statistically significant brighter appearing skin at 14 days (p = 0.007) and more youthful looking skin on Days 14 and 30 (p = 0.003 and 0.04, respectively).ConclusionsThis study demonstrates that Renewosome™ technology provides statistically significant post‐laser clinical recovery over silicone gel for reducing crusting, and downtime. Subjects reported less diary days of symptoms of pain/tenderness, redness, crusting/flaking, bruising, and itching in the first 14 days compared to the control group. CALM also demonstrated statistically significant improvements in brighter and more youthful appearing skin. CALM is safe and well tolerated.

Background and Objective: The association of non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) with intensive care unit (ICU) admissions and the need for mechanical ventilation and disease severity in COVID-19 patients. Material and Methods: A systematic literature review was conducted on the databases: Cochrane, Embase, PubMed, ScienceDirect, and the Web of Science from January 2019 to June 2022. Studies evaluating MAFLD using laboratory methods, non-invasive imaging, or liver biopsy were included. The study protocol was registered in PROSPERO (ID CRD42022313259), and PRISMA guidelines were followed. The NIH quality assessment tool was used for quality assessment. RevMan version 5.3 software was used for pooled analysis. A sensitivity analysis was performed to assess the result’s stability. Results: A total of 37,974 patients from 17 studies were assessed for the association between MAFLD and ICU admission. A total of 3396 COVID-19 patients required ICU admission: 1236 (20.41%) in the MAFLD group and 2160 (6.77%) in the non-MAFLD group. The odds ratio was 1.86 for ICU admission, p = 0.007, and a (95% CI) of [1.18–2.91]. A total of 37,166 patients from 13 studies were included in the need for invasive mechanical ventilation analysis. A total of 1676 patients required mechanical ventilation: 805 in the MAFLD group (14.20% of all MAFLD patients) and 871 patients in the non-MAFLD group (2.76% of all non-MAFLD patients). The odds ratio was 2.05, p = 0.02, and a (95% CI) of [1.12–3.74]. A total of 5286 patients from 14 studies were included in the COVID-19 disease severity analysis. Severe COVID-19 was seen in 1623 patients, with 33.17% (901/2716) of MAFLD patients and 28.09% (722/2570) of non-MAFLD patients having severe disease. The odds ratio was 1.59 for disease severity, p = 0.010, and a (95% CI) of [1.12–2.26]. Conclusions: Our meta-analysis suggests that there are significantly increased odds of ICU admissions, a need for invasive mechanical ventilation, and disease severity in MAFLD patients who acquire COVID-19.

Importance Lensectomy with primary intraocular lens (IOL) implantation is often used in the management of nontraumatic pediatric cataract, but long-term data evaluating the association of age and IOL location with the incidence of complications are limited. Objective To describe the incidence of complications and additional eye surgeries through 5 years following pediatric lensectomy with primary IOL implantation and association with age at surgery and IOL location. Design, Setting, and Participants This prospective cohort study used Pediatric Eye Disease Investigator Group cataract registry data from 61 institution- and community-based practices over 3 years (June 2012 to July 2015). Participants were children younger than 13 years without baseline glaucoma who had primary IOL implantation (345 bilateral and 264 unilateral) for nontraumatic cataract. Data analysis was performed between September 2021 and January 2023. Exposures Lensectomy with primary IOL implantation. Main Outcome and Measures Five-year cumulative incidence of complications by age at surgery (<2 years, 2 to <4 years, 4 to <7 years, and 7 to <13 years) and by IOL location (sulcus vs capsular bag) were estimated using Cox proportional hazards models. Results The cohort included 609 eyes from 491 children (mean [SD] age, 5.6 [3.3] years; 261 [53%] male and 230 [47%] female). Following cataract extraction with primary IOL implantation, a frequent complication was surgery for visual axis opacification (VAO) (cumulative incidence, 32%; 95% CI, 27%-36%). Cumulative incidence was lower with anterior vitrectomy at the time of IOL placement (12%; 95% CI, 8%-16%) vs without (58%; 95% CI, 50%-65%), and the risk of undergoing surgery for VAO was associated with not performing anterior vitrectomy (hazard ratio [HR], 6.19; 95% CI, 3.70-10.34; P < .001). After adjusting for anterior vitrectomy at lens surgery, there were no differences in incidence of surgery for VAO by age at surgery (<2 years, HR, 1.35 [95% CI, 0.63-2.87], 2 to <4 years, HR, 0.86 [95% CI, 0.44-1.68], 4 to <7 years, HR, 1.06 [95% CI, 0.72-1.56]; P = .74) or by capsular bag vs sulcus IOL fixation (HR, 1.22; 95% CI, 0.36-4.17; P = .75). Cumulative incidence of glaucoma plus glaucoma suspect by 5 years was 7% (95% CI, 4%-9%), which did not differ by age after controlling for IOL location and laterality. Conclusions and Relevance In this cohort study, a frequent complication following pediatric lensectomy with primary IOL was surgery for VAO, which was associated with primary anterior vitrectomy not being performed but was not associated with age at surgery or IOL location. The risk of glaucoma development across all ages at surgery suggests a need for long-term monitoring.

Injection of A-MSC-derived EVs harvested from patients who are lean can resolve myocardial injury in mice with experimental renovascular hypertension more effectively than A-MSC-derived EVs from patients with obesity. These observations underscore and might have important ramifications for the self-healing capacity of patients with obesity and for the use of autologous EVs as a regenerative tool.

Abstract Background The relationship between body mass index (BMI) and outcomes in patients with nonalcoholic fatty liver disease (NAFLD) is not well defined. This study aimed to assess the presentations, outcomes, and development of liver-related events (LREs) and non-LREs in patients with NAFLD stratified by BMI. Methods Records of NAFLD patients from 2000–2022 were reviewed. Patients were categorized as lean (18.5–22.9 kg/m2), overweight (23–24.9 kg/m2), and obese (>25 kg/m2) based on BMI. Stage of steatosis, fibrosis, and NAFLD activity score were noted in the patients undergoing liver biopsy in each group. Results Out of 1051 NAFLD patients, 127 (12.1%) had normal BMI, 177 (16.8%) and 747 (71.1%) were overweight and obese, respectively. Median [interquartile range] BMI was 21.9 [20.6–22.5], 24.2 [23.7–24.6], and 28.3 [26.6–30.6] kg/m2 in each group, respectively. Prevalence of metabolic syndrome and dyslipidemia were significantly higher in the obese. Obese patients had significantly higher median [interquartile range] liver stiffness (6.4 [4.9–9.4] kPa) than overweight and lean subjects. A higher proportion of obese patients had significant and advanced liver fibrosis. At follow-up, there were no significant differences in the progression of liver disease, new LREs, coronary artery disease, or hypertension across the BMI groups. Overweight and obese patients were more likely to develop new-onset diabetes by follow-up. The mortality rates in the three groups were comparable (0.47, 0.68, and 0.49 per 100 person-years, respectively), with similar causes of death (liver-related vs non-liver-related). Conclusions Patients with lean NAFLD have similar disease severity and rates of progression as the obese. BMI is not a reliable determinant of outcomes in NAFLD patients. Key messages What is already known on this topic What this study adds How this study might affect research, practice, or policy

9069 Background: With the emergence of effective targeted-therapies for KRAS G12C, and the development of promising agents for KRAS G12V and G12D among others, the identity of unique KRAS mutations in non-small cell lung cancer (NSCLC) has become increasingly relevant. Acquired KRAS mutations are a known mechanism of resistance observed across driver mutation-positive (DM+) NSCLC. The incidence and diversity of these acquired alterations, and whether they differ from those observed in de novo KRAS-mutated NSCLC, is unknown. Methods: NSCLC molecular profiles were obtained using next-generation sequencing (Caris Life Sciences) with paired whole-transcriptomic sequencing (Illumina NovaSeq) and immunohistochemistry (Caris Life Sciences). Demographic data were abstracted from medical records. KRAS mutation diversity was defined for de novo KRAS-mutated ( KRASmt) NSCLC ( KRAS as only identified driver – KRASmt_dn) and DM+ NSCLC with acquired KRAS mutations (concurrent KRASmt with other known driver – KRASmt_acq). Fisher’s exact test was used to compare the distribution of unique KRAS mutations between the groups. Due to the unique biology of NSCLC with class II/III BRAF mutations, this subset was removed from the KRASmt_acq subgroup for the final analysis. Results: A total of 5932 KRASmt NSCLC samples were identified, among which 5879 were KRASmt_dn and 53 were KRASmt_acq (see table). The distribution of unique KRAS mutations was not significantly different between groups (p = 0.14). Within the KRASmt_dn group, KRAS G12C was most common (40%), followed by G12V (19%), G12D (14%), G12A (7%) and Q61H/G13C (4% each). In the KRASmt_acq group, KRAS G12C was most common (30%), followed by G12D (19%), G12V (17%), Q61H (11%), G12A (7%), and G13C (6%). The most common observed driver mutations in the KRASmt_acq group were EGFR (38%) and MET (30%). In the EGFR group, KRAS G12D (25%), Q61H/G12C (20% each), G12V/G13C (10% each), and G12F/A/R (5% each) were observed. In the MET group, KRAS G12C (25%), G12D/V/A (19% each), Q61H (12%) and G12S (6%) were seen. Among 7 patients with a documented history of smoking in the KRASmt_acq group, KRAS G12D and Q61H were most common (29% each), followed by G12V/F and G13C (14% each). Conclusions: While the distribution of unique KRAS mutations did not differ significantly between KRASmt_dn and KRASmt_acq groups, acquired KRAS mutations were seen across DM+ NSCLC subsets, among which the frequency of observed mutations appeared to vary. The functional and immunological significance of these mutations, and their impact on clinical outcomes, warrants further investigation. [Table: see text]

TPS7587 Background: Covalent (c) Bruton tyrosine kinase inhibitors (BTKi) have transformed the management of MCL, but these agents are not curative. cBTKi share pharmacologic liabilities (e.g., low oral bioavailability, short half-life), which collectively may lead to suboptimal BTK target coverage especially in rapidly proliferating tumors with high BTK protein turnover such as MCL, which can manifest as acquired resistance to BTKi. Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi, has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval regardless of intrinsic rate of BTK turnover. In the phase 1/2 BRUIN study, pirtobrutinib demonstrated promising durable overall response rates and was well tolerated in patients (pts) with MCL regardless of prior therapy (including cBTKi), number of prior lines of therapy, or reason for prior cBTKi discontinuation. Pirtobrutinib was approved by the FDA in January 2023 for R/R MCL after 2 prior lines of therapy including a BTKi. The objective of this study is to establish whether pirtobrutinib is superior to investigator’s choice of cBTKi in pts with previously treated, BTKi naïve MCL. Methods: BRUIN MCL-321 (NCT04662255) is a randomized, open-label, global phase 3 study comparing pirtobrutinib monotherapy versus investigator’s choice of cBTKi monotherapy (ibrutinib, acalabrutinib, or zanubrutinib) in pts with previously treated, BTKi naïve MCL. Approximately 500 pts will be randomized 1:1 and stratified by sMIPI risk (low/intermediate vs high), comparator BTKi (ibrutinib vs acalabrutinib/zanubrutinib), and number of prior lines of therapy (1 vs ≥ 2). Enrollment for this study is ongoing. Adults with a diagnosis of MCL who have received ≥ 1 prior line of systemic therapy for MCL and are BTKi naïve are eligible. Pts must have measurable disease by imaging per Lugano criteria and have progressed on or relapsed following the most recent line of therapy. A history of current or prior CNS involvement, significant cardiovascular disease, stroke or intracranial hemorrhage within 6 months of randomization, and autologous stem cell transplant (SCT), allogeneic SCT or chimeric antigen receptor (CAR) T-cell therapy within 60 days of randomization are key exclusion criteria. Progression-free survival (PFS) per Lugano criteria assessed by an independent review committee is the primary endpoint. Overall response rate, duration of response, investigator-assessed PFS per Lugano criteria, overall survival, event-free survival, time to treatment failure, time to next treatment, PFS2 (time from randomization to disease progression on next line of treatment or death from any cause), safety and tolerability, and pt reported outcomes are secondary endpoints. Clinical trial information: NCT04662255 .

e13683 Background: Access to specialized cancer care varies by place of residence, partly due to differences in geographic proximity to designated cancer centers. Telehealth services can help alleviate some of these geographic disparities. In response to the COVID-19 pandemic, Medicare telehealth services were expanded rapidly. In this study, we sought to describe the geographic variations in Medicare telehealth utilization and their relationship with locations of designated cancer centers in the United States. We hypothesized that differences in telehealth utilization might be reflective of barriers to telehealth access for Medicare beneficiaries in these regions. Methods: We used the Medicare Telehealth Trends data file and calculated the proportion of Medicare users who used a telehealth service (% Telehealth Users) across all quarters of 2021. To obtain % Telehealth Users in a state, the number of telehealth users were divided by the total number of telehealth-eligible users. Then, using % Telehealth Users as a metric of telehealth utilization, we ranked all US states by overall % Telehealth Users, and % Telehealth Users in rural and urban locations. Finally, we correlated these ranks with the presence of an NCI (National Cancer Institute) Designated Cancer Center within the states. Results: The % Telehealth Users ranged from 15%-53% overall, 16%-54% for rural locations, and 14%-54% for urban locations, across lowest ranked to highest ranked states. The 5 lowest ranking states and their respective % Telehealth Users overall were- Wyoming (20%), Montana (20%), Iowa (20%), South Dakota (18%), Nebraska (17%), and North Dakota (15%). The lowest ranking states in terms of rural % Telehealth Users were Montana, Kansas, Iowa, Tennessee, Wyoming (19% each), and South Dakota and Nebraska (16% each). The lowest ranking states in terms of urban % Telehealth Users were Montana (20%), Wyoming (20%), Nebraska (19%), South Dakota (16%), and North Dakota (14%). 4 out of 6 states overall, 3 out of 7 in the rural category, and 4 out of 5 states in the urban category that were ranked the lowest in telehealth utilization did not have an in-state NCI designated cancer center. Conclusions: Telehealth services can bridge gaps in access to specialty cancer care for patients that do not live in geographic proximity of cancer centers. However, regions lacking geographic proximity to cancer centers were also regions with poorest telehealth utilization. Advocacy and policy efforts directed towards increasing access to telehealth can ensure equitable and timely access to specialized cancer care in these regions of need.