Citations

Background: Electrocardiogram (EKG) is a commonly used diagnostic tool for the evaluation of the electrical activity of the heart. The purpose of this study was to assess the knowledge and interpretation proficiency of EKG among healthcare professionals (HCPs) in Pakistan. Methods: This prospective cross-sectional study was conducted among HCPs working in different healthcare settings. A structured questionnaire was used to assess the participants’ theoretical knowledge and ability to interpret EKG findings. The data were analyzed using descriptive statistics and χ2 tests. The study indicates that EKG knowledge and interpretation proficiency among HCPs in Pakistan is unsatisfactory. The inadequacy of training periods of EKG training sessions and insufficient participation of HCPs in offered training opportunities put forward the need for the formation and introduction of better structured and efficient EKG training programmes. Results: A total of 511 HCPs participated in the study, 28% of whom reportedly had received formal training for EKG interpretation. About 80% of the participants correctly identified theoretical questions pertaining to EKG, while 58% of the participants were able to accurately interpret EKG findings, and most HCPs (69.9%) read fewer than ten EKGs per week. Conclusion: This study demonstrates a lack of expertise and a poor understanding of EKG in HCPs of Pakistan. The low level of EKG knowledge and interpretation proficiency among HCPs may lead to diagnostic errors and poor patient outcomes. Therefore, efforts should be made to improve EKG education and training among HCPs in Pakistan.

Background Postprandial sleepiness refers to the state of excessive drowsiness that occurs after consuming a meal. This transient phenomenon is experienced by many individuals, often leading to decreased productivity and impaired cognitive performance. This study examined the effect of a whole-food plant-based (WFPB) diet on postprandial sleepiness. Methods Ten participants who had postprandial sleepiness who were on a typical American diet transitioned to a WFPB dietary pattern for 21 days. Postprandial sleepiness was assessed using the Epworth Sleepiness Scale (ESS) questionnaire, focusing on Q7 “sitting quietly after lunch without alcohol” as well as Q5 “lying down to rest in the afternoon when circumstances permit.” Results The participants had a mean age of 44 +/− 15 years, with 30% being male. There was a statistically significant reduction in sleepiness measured by ESS Q7 (median change = −1, P = .012) and ESS Q5 (median change = −1.5, P = .008). Moreover, there was a statistically significant decrease in overall ESS scores (median change = −8.0, P = .006), and weight (median change = −2.9 kg, P = .006). Conclusion Participants demonstrated significant improvement in postprandial sleepiness-related situations. Our findings showed that the WFPB diet may have potential benefits for reducing postprandial and overall daytime sleepiness.

Abstract The requirement of community outreach and engagement (COE) as a major component of the National Cancer Institute (NCI) Cancer Center Support Grant has had an enormous impact on the way NCI-designated cancer centers identify, investigate, and address the needs of their catchment area (CA) communities. Given the wide-ranging diversity of our nation, COE’s scope of work (SOW) is extremely demanding and complex. Yet, COE is often marginalized and viewed as void of scientific methods when, in fact, it requires specialized scientific knowledge and a broad range of proficiencies. Black COE scientific directors may be particularly attuned to this marginalization as they have often confronted workplace inequities that resemble the health inequities observed within their cancer center’s CA. Thus, Black COE leaders are uniquely positioned to offer insight on the past, present, and future of COE. Key areas discussed include the low involvement of minoritized group members and those with appropriate expertise in national COE leadership; the lack of established, consistent criteria for evaluation of COE components and qualifications of evaluators; the need for substantial financial investment in COE; potential misalignment of community priorities and cancer center objectives; professional development and growth of COE staff and leaders; the expanding scope of COE across their respective cancer centers and CAs; and the need for center-wide involvement in COE and an “all-hands-on-deck” approach. These areas warrant thoughtful dialogue as COE evolves, for the benefit and success of all COE leaders. However, this dialogue must include diverse voices representing similarly diverse stakeholders at every level.

AbstractA 3D‐printed array of hollow microneedles (HMNs) is designed and fabricated using a high‐resolution stereolithography 3D printer and assembled with a 3D‐printed reservoir that incorporates a Luer lock mechanism, ensuring standard and secure connection to syringes. The proof‐of‐concept needle designs consist of half‐eccentric and concentric conical tip shapes, each arrayed with two different interspacing values. After the geometrical features of the devices are characterized, the devices are tested ex vivo in porcine skin to evaluate the impact of tip shape and interspacing on the depth of penetration and the efficacy of the devices in delivering fluids (such as tattoo ink) into the dermis. Overall, the 3D‐printed HMNs can deliver fluids into the target layer of skin. Refinement of the design is ongoing with the ultimate aim to provide alternatives for intradermal drug delivery and diagnostic imaging, such as superficial lymphography.

AbstractINTRODUCTIONThe contribution of neuropsychological assessments to risk assessment for incident dementia is underappreciated.METHODSWe analyzed neuropsychological testing results in dementia‐free participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined associations of index domain–specific neuropsychological test performance with incident dementia using cumulative incidence curves and Cox proportional hazards models.RESULTSAmong 5296 initially dementia‐free participants (mean [standard deviation] age of 75.8 [5.1] years; 60.1% women, 22.2% Black) over a median follow‐up of 7.9 years, the covariate‐adjusted hazard ratio varied substantially depending on the pattern of domain‐specific performance and age, in an orderly manner from single domain language abnormalities (lowest risk) to single domain executive or memory abnormalities, to multidomain abnormalities including memory (highest risk).DISCUSSIONBy identifying normatively defined cognitive abnormalities by domains based on neuropsychological test performance, there is a conceptually orderly and age‐sensitive spectrum of risk for incident dementia that provides valuable information about the likelihood of progression.Highlights Domain‐specific cognitive profiles carry enhanced prognostic value compared to mild cognitive impairment. Single‐domain non‐amnestic cognitive abnormalities have the most favorable prognosis. Multidomain amnestic abnormalities have the greatest risk for incident dementia. Patterns of domain‐specific risks are similar by sex and race.

Cardiogenic shock is the most common cause of mortality in patients with acute myocardial infarction with an increase in incidence over the last 15-years. Recent classification systems of cardiogenic shock (CS) have improved categorization of patients into subsets of acuity and begun to integrate phenotypes and etiologies in addition to risk modifiers. Early revascularization with PCI or CABG has been the most important advance in the management of AMI-CS patients with improvements in survival. Despite this initial progress, mortality remains high at approximately 40%, with a significant proportion of patients dying of neurological causes, especially in the cohort with cardiac arrest and multi-organ dysfunction despite cardiac recovery. Mechanical circulatory support devices are an attractive strategy to ameliorate the cardio-metabolic spiral but have thus far failed to show survival benefits in randomized trials during revascularization of AMI-CS patients with IABP and ECMO use, although many aspects of their use have yet to be studied, including their role as part of an escalation or bridging strategy along the continuum of CS care. Randomized trials in Impella percutaneous LVAD use are pending. Cardiac arrest patients represent an important cohort with specific challenges of care and familiarity with management including the use of mechanical CPR devices, temperature optimization, MCS use and pharmacotherapy issues are critical to successful outcomes.

3053 Background: Recently, early studies have identified circulating stromal cells (CStCs), i.e. Cancer Associated Macrophage-Like cells (CAMLs), in patients (pts) with newly diagnosed invasive cancers, which are phagocytic myeloid immune cells emanating from primary tumors. However, no study has evaluated CAMLs as a pan solid tumor screening tool nor their clinical impact on pt outcomes. We analyzed the blood of untreated newly diagnosed cancer pts (n=441), or in non-malignant conditions (i.e. pancreatic cysts, n=77), or healthy controls (n=100). We found that CAMLs are prevalent (82%) in cancer pt blood, absent in healthy controls (0%) and less common in non-malignant conditions (36%), with correlations to worse clinical outcomes. Methods: Anonymized peripheral blood was taken from n=441 pts before or after confirmation of invasive malignancy [stage I (n=105), stage II (n=125), stage III (n=114), stage IV (n=97) with pathologically confirmed lung (n=84), pancreas (n=61), breast (n=73), prostate (n=65), esophageal (n=34), Renal Cell (n=29), Sarcoma (n=27), or Other (n=68). In addition, anonymized blood was taken from pts with untreated non-malignant conditions including benign breast masses (n=19), Lupus (n=11), liver Cirrhosis (n=6), rising PSA (n=24), or other benign mass (n=17); and from healthy control volunteers (n=100). CAMLs were isolated by CellSieve microfiltration, defined as enlarged polyploid cells with cytokeratin+ and/or CD45/CD14+. Pts were monitored for 0-8 years (median=2.6) for progression free survival (PFS) and overall survival (OS). Results: CAMLs were found in 82% of all cancer pts averaging 5.4 CAMLs, specifically, in 66% of Stage I, 85% Stage II, 84% Stage III, and 92% Stage IV. No CAMLs were found in any healthy controls, but were in 36% of non-malignant pts. CAML sensitivity in cancer vs healthy was 82% (CI95% 78-85%), specificity=100% (CI95% 96-100%), PPV=100% (CI95% 99-100%), NPV=55% (CI95% 50-60%). CAML sensitivity in cancer vs benign was 82% (CI95% 78-85%), specificity=64% (CI95% 32-44%), PPV=93% (CI95% 90-95%), NPV=38% (CI95% 32-44%). CAML presence was significantly associated with worse PFS (HR=2.0, 95%CI 1.4-2.9, p<0.0001) & OS (HR=2.2, 95%CI 1.4-3.3, p=0.0004), with engorged phagocytic CAMLs (>50um), highly significant for worse PFS (HR=3.3, 95%CI 2.5-4.5, p<0.0001) & OS (HR=3.0, 95%CI 2.1-4.3, p<0.0001). Further, in benign pts positive for CAMLs, 2 pts were in situ, 16 had histologies with increased cancer risk (i.e. IPMN, atypical hyperplasia), and 5 pts died within 3 years. Conclusions: CAMLs appear to be a highly sensitive blood based biomarker that can identify invasive carcinoma in all stages of cancer regardless of subtype, but are not found in healthy controls & rare in non-malignant conditions. Further, enlarged phagocytic CAMLs appeared to correlate with shorter PFS and OS prior to treatment induction.

3051 Background: Clonal hematopoiesis (CH), characterized by the presence of somatic mutations in blood cells, can be found in cancer-related genes when sequencing tumor tissue or plasma samples. Inability to distinguish somatic, tumor-derived mutations from CHm can lead to inaccurate treatment decisions. In this prospective study, we confirmed potential CHm in solid tumors by sequencing and analysis of paired matched normal (PMN) specimens. Methods: We prospectively enrolled 56 patients diagnosed with advanced cancer, including lung (16), colorectal (13), breast (10), gastric (7), ovarian (2), pancreatic (2), liver (2), cervix (1), uterine (1), fallopian tube (1), and perihilar bile duct (1). Targeted next-generation sequencing using a 523 gene panel was performed on paired formalin-fixed paraffin-embedded (FFPE) and circulating tumor DNA (ctDNA) samples. Additionally, whole exome sequencing was performed on PMN buffy coat samples. Analysis of all three specimens was performed to classify somatic mutations as tumor-derived or CHm. Results: We identified 21 potential CHm within the FFPE and ctDNA samples of 13 patients (23.2% of the cohort) with lung (7), breast (2), liver (2), colorectal (1), and gastric (1) cancers. CHm were further confirmed when present in buffy coat samples. The VAF of CHm in FFPE and ctDNA samples exhibited a wide range, spanning from 0.85% to 38.4%, with 7 of those identified at <2% VAF. For these same aberrations, VAF in buffy coat samples ranged from 1.6% to 48%, with seven mutations exhibiting VAF levels <5%. Four of these CHm were classified as oncogenic or likely oncogenic. Four CHm, including an oncogenic TP53 mutation, were identified in the oldest patient (75 years old, lung cancer), while an oncogenic DNMT3A mutation was detected in the youngest patient (42 years old, breast cancer). Both had a 30-year history of smoking. Conclusions: Our findings identified somatic CHm in a substantial subset (23.2%) of solid tumors, with four identified as oncogenic or likely oncogenic mutations. The broad spectrum of VAFs for CHm suggests that using VAF as a cut-off to exclude likely CHm may be unreliable. The low VAF CHm found in matched normal specimens indicates low-pass sequencing may not detect critical CHm, even in paired analysis. The diverse age range of patients with CHm (42 to 75 years old) suggests that CHm are not restricted to older populations, and that additional factors, such as smoking history, may play a role. These findings underscore the importance of incorporating routine PMN buffy coat sequencing into clinical practice, to identify somatic CHm that can impact personalized cancer treatment strategies.

Abstract Background This is a phase II subprotocol of the NCI-COG Pediatric MATCH study evaluating vemurafenib, a selective oral inhibitor of BRAF V600 mutated kinase, in patients with relapsed or refractory solid tumors harboring BRAF V600 mutations. Methods Patients received vemurafenib at 550 mg/m2 (maximum 960 mg/dose) orally twice daily for 28-day cycles until progression or intolerable toxicity. The primary aim was to determine the objective response rate and secondary objectives included estimating progression-free survival and assessing the tolerability of vemurafenib. Results Twenty-two patients matched to the subprotocol and 4 patients (18%) enrolled. Primary reasons for non-enrollment were ineligibility due to exclusions of low-grade glioma (n = 7) and prior BRAF inhibitor therapy (n = 7). Enrolled diagnoses were one each of histiocytosis, ameloblastoma, Ewing sarcoma, and high-grade glioma, all with BRAF V600E mutations. Treatment was overall tolerable with mostly expected grade 1/2 adverse events (AE). Grade 3 or 4 AE on treatment were acute kidney injury, hyperglycemia, and maculopapular rash. One patient came off therapy due to AE. One patient (glioma) had an objective partial response and remained on protocol therapy for 15 cycles. Conclusion There was a low accrual rate on this MATCH subprotocol, with only 18% of those who matched with BRAFV600 mutations enrolling, resulting in early termination, and limiting study results (ClinicalTrials.gov Identifier: NCT03220035).