Positive Uptake Research Articles

Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasinglyrecognized cause of heart failure with preserved ejection fraction (HFpEF), which may be diagnosed non-invasively using 99 mTc 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy-based diagnostic criteria. Our aim was to determine the prevalence of ATTR-CM in an undifferentiated HFpEF cohort with a DPD scintigraphy-based screening protocol. Patients with HFpEF [ejection fraction (EF) ≥50%] aged ≥60years and no prior evaluation for cardiac amyloidosis or known monoclonal gammopathy attending a regional cardiology network were screened with DPD scintigraphy. Patients with positive myocardial uptake (Perugini grade 2 or 3) were tested for a monoclonal protein and transthyretin gene variant. Eighty-six subjects were prospectively enrolled: 56% female, mean age 77±8years, 63% New York Heart Association (NYHA) Class III and median N-terminal pro-brain natriuretic peptide (NT-proBNP) 1766ng/L [inter-quartile range (IQR) 731-3703]. DPD scintigraphy was positive in seven patients (8%). Monoclonal gammopathy of undetermined significance was present in one out of seven patients, and no pathogenic TTR gene variant was identified. The prevalence of wild-type ATTR-CM was 8% of this cohort. Compared with the HFpEF DPD scintigraphy-negative cohort, DPD scintigraphy-positive patients were older (86±3 vs. 76±8years), more frequently male (16% vs. 2%, P=0.02), and had significantly greater left ventricular (LV) wall thickness (16 vs. 12mm; P=0.002) and higher high-sensitivity troponin levels at diagnosis [78ng/L (IQR 21-116) vs. 11ng/L (IQR 9-17); P<0.001]. In an undifferentiated HFpEF cohort, 8% were found to have wild-type ATTR-CM using a DPD scintigraphy-based screening protocol. Screening undifferentiated HFpEF patients is associated with a significant diagnostic yield, which can be further increased by targeting older males with increased LV wall thickness and elevated high-sensitivity troponin levels.

Chronic Disseminated Candidiasis among Pediatric Cancer Patients: The Hidden Threat

Abstract Background Chronic disseminated Candidiasis (CDC) is a severe invasive fungal infection observed during neutrophil recovery in patients with acute leukemia treated with intensive chemotherapy. Clinical manifestations include persistent fever under broad-spectrum antibiotics and abdominal discomfort. HSC is characterized by the presence of nodular lesions in the liver, spleen, and other organs (lungs, kidneys, and skin) on radiological imaging. Methods The retrospective study was conducted from 2013 - 2022 including all pediatric hematological patients diagnosed with chronic disseminated candidiasis admitted and treated in Children’s Cancer Hospital Egypt (CCHE). Data included primary diagnosis, clinical presentation, microbiological, radiological, and treatment data. Results Three hundred fifty (350) pediatric cancer patients were diagnosed with candidemia. The median age was four years (4 months- 18 years). Chronic dissemination candidiasis (CDC) was reported in 30(9%) of our patients. The most affected organs were Liver (19 patients), spleen (13), renal (13), cautelous (13), brain (2) and retina (2). Candida tropicalis was the most common isolated spp. from blood/tissue culture (24 patients) followed by C. parapsilosis (3 patients). The primary diagnosis in patients with CDC was ALL (24 Patients) while (4 patients) has AML. CDC was developed on top of antifungal prophylaxis in 7 patients (24%): liposomal-amho B (3 patients), Micafungin (3 patients) and voriconazole (1 patient). Candida tropicalis was the most common isolated spp. from blood/tissue culture (80%). Steroid as treatment for CDC immune reconstitution syndrome done in around 50% of patients (Persistent fever with neutrophil recovery, absent progressive clinical/radiological findings). PET-CT was done in 10 patients with positive uptake in all cases, was helpful in resuming intensive chemotherapy in six patients despite persistent lesions in CT and was used to stop antifungal treatment despite positive radiological lesions in CT in three patients. The first line of treatment was echinocandin (53%) and liposomal ampho-B (46%) with overall mortality among CDC patients were 30%. Conclusion CDC is still a hidden threat among pediatric patients with still high mortality rate. Antifungal stewardship through screening and Rapid diagnosis using non-culture diagnostics are needed. PET scan is a helpful tool for diagnosis and response assessment and can add to treatment decision. Figure 1. Chronic Disseminated Candidiasis among Pediatric Cancer patients.

Addressing disparity in attitudes and utilization of family planning among married couples in the pastoralist community of Fentale District, Eastern Ethiopia.

Despite progress in national reproductive health programs, pastoralist regions like Fentale District in Eastern Ethiopia face challenges with low contraceptive coverage, attributed to insufficient positive attitudes and uptake among couples. This cross-sectional study was conducted from October 1 to December 25, 2021, in Fentale District, Eastern Ethiopia. It involved 1,496 couples selected using multistage sampling. Data were entered into EPI Data and analyzed with SPSS (v23.0) and STATA (v14.0), employing descriptive statistics, bivariate analysis, and binary logistic regression to identify predictors of contraceptive attitudes and use. The study's response rate was 93.8%, with 1,404 pastoralist couples participating, equally split between women and men. A nomadic-pastoralist lifestyle was common (64.6%), and family planning discussions were rare (93.2%). Gender disparities in contraceptive attitudes and use were evident. Contraception use was reported by 27.4%, with women (41.2%) outnumbering men (13.5%). Women showed more positive attitudes towards contraception (87.9% vs. 31.9% for men). Only 33% had favorable attitudes towards different contraceptive methods, with women more likely to be positive. Modern contraception use was low (18.2%), with women (34.8%) predominating over men (1.7%). Among users, women had a more favorable attitude (78.5% vs. 6.6% for men). Health extension workers were key information providers. Predictors of contraceptive attitudes and use included sex, education, occupation, electronic device ownership, migration frequency, treatment preferences, and family planning discussions. The limited positive attitude towards and use of family planning in Fentale District may stem from unfavorable attitudes, low adoption, and couple disparities. Key factors include gender, education, occupation, electronic device ownership, migration, treatment preferences, and family planning discussions. Targeted educational campaigns for men are needed to address these issues and reduce the gender gap in contraceptive attitudes and use.

Clinical Value of Dual Tracer PET Imaging With 68Ga-PSMA and 18F-FDG in Patients With Metastatic Prostate Cancer

In this study, we retrospectively analyzed the imaging characteristics of dual-tracer 68Ga-prostate specific membrane antigen (PSMA) and 18F-flurodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in metastatic prostate cancer (mPCa) patients. We analyzed the uptake modes of the dual tracers, explored clinical pathological parameters affecting the 18F-FDG uptake in the lesions, and evaluated their prognostic implications for prostate specific antigen progression-free survival (PSA-PFS). A total of 41 mPCa patients who underwent dual-tracer PET/CT (68Ga-PSMA and 18F-FDG) scans between September 2021 and January 2024 were retrospectively enrolled. One patient had negative uptake of both PSMA and FDG. According to the uptake patterns of the 2 tracers, the other patients, 40 in total, were categorized in 2 groups, including group A consisting of 33 cases who showed PSMA and FDG dual and those who showed FDG only avidity, and group B consisting of 7 cases who showed PSMA avidity only. Comparative analyses of clinical pathological characteristics between group A and group B were conducted. The relationship between various parameters and PSA-PFS was analyzed by the Kaplan-Meier method. A total of 26 patients (63.4%) were diagnosed with metastatic castration-resistant prostate cancer (mCRPC), and 38 cases (92.7%) had a Gleason score of 8-9. Bone metastasis, the predominant type of distant metastasis, occurred in 36 cases (87.8%). The skeletal and distant lymph node metastases mostly showed a dual positive uptake pattern for both PSMA and FDG (85.7% [24/28] and 81.8% [9/11]). 37.5% (3/8) of the metastases to organs showed FDG only positive uptake pattern. The serum levels of prostate specific antigen (PSA) in group A were significantly higher than those in group B (P=0.013). A total of 13 patients of special pathological classification (intraductal carcinoma and neuroendocrine differentiation) were all found to be in group A. Among the 41 cases, 16 were lost to follow-up. Of the 25 patients who completed follow-up, 9 patients, with a median PSA value of 104 ng/mL, experienced PSA progression, while the 16 other patients, with a median PSA of 0.34 ng/mL, did not incur any PSA progression. There was significant difference in the median PSA between patients showing PSA progression and those who did not show PSA progression (P<0.001). Kaplan-Meier survival analysis revealed that the median PSA-PFS of patients of specific pathological classifications was 7 months, which was shorter than the 16 months of the patients with typical prostate cancer, with the difference between the two groups being statistically meaningful (P=0.043). The median PSA-PFS for group A was 30 months. With more than half of the patients in the group not experiencing any PSA progression, group B did not reach the median PSA-PFS (P=0.645). Dual-tracer PET/CT imaging with 68Ga-PSMA and 18F-FDG commonly exhibits avidity for both tracers in mPCa. Serum PSA level is a reliable biomarker for predicting FDG-positive lesions. mPCa presented with intraductal carcinoma and neuroendocrine differentiation tends to exhibit FDG avidity and is more susceptible to PSA progression.

Knowledge, attitudes, practices, and sociocultural factors influencing cervical cancer screening and vaccination among women in rural communities of Gujarat: A mixed-methods study.

Cervical cancer is a leading cause of cancer mortality among women in India. Screening can help in early detection and improve outcomes. However, uptake remains low, especially in rural areas. Understanding multidimensional factors influencing screening in local contexts is essential to promote equitable access. This study examined knowledge, attitudes, practices, and sociocultural factors associated with cervical cancer screening and vaccination in rural India. A mixed methods study was conducted among 400 women aged 18-60 years in rural Maharashtra. Quantitative data were collected on knowledge, attitudes, and screening practices by using a structured questionnaire. Qualitative data were gathered through in-depth interviews with 30 participants on perspectives influencing screening. Quantitative data were analyzed using descriptive statistics and logistic regression. Thematic analysis was done for qualitative data. The integration provided complementary insights. Quantitative results showed poor knowledge (17% had good knowledge) and positive attitudes (64%) but low screening uptake (9%). Qualitative findings revealed limited awareness, stigma around gynecological exams, gender inequities, fear, fatalism, and low prioritization of self-care as screening barriers. Multifaceted strategies addressing knowledge gaps, gender roles, stigma, and access are required to improve cervical cancer screening in marginalized rural communities. Mixed methods provide comprehensive evidence for designing context-specific interventions.

Evaluating the student performance prediction and action framework through a learning analytics intervention study

AbstractLearning analytics intervention (LAI) studies aim to identify at-risk students early during an academic term using predictive models and facilitate educators to provide effective interventions to improve educational outcomes. A major impediment to the uptake of LAI is the lack of access to LAI infrastructure by educators to pilot LAI, which typically requires substantial institution-wide efforts and investment to collect related data sets and develop accurate predictive models that identify at-risk students and also provide tools to facilitate interventions. This paper presents a novel LAI framework, termed Student Performance Prediction and Action (SPPA), that facilitates educators to seamlessly provide LAIs in their courses avoiding the need for large-scale institution-wide efforts and investments. Educators develop course-specific predictive models using historical course assessment data. In learning analytics, providing effective interventions is a challenge. SPPA utilises pedagogy principles in course design and interventions to facilitate effective interventions by providing insights into students’ risk levels, gaps in students’ knowledge, and personalised study/revision plans addressing knowledge gaps. SPPA was evaluated in a large undergraduate course on its ability to predict at-risk students and facilitate effective interventions as well as its ease of use by academics. The results are encouraging with high performance of predictive models, facilitating effective interventions leading to significant improved educational outcomes with positive feedback and uptake by academics. With its advantages, SPPA has the potential to catalyse and influence wide-scale adoption in LAIs.

COVID-19 vaccination attitudes and uptake: A sociocultural perspective focusing on parents and peers.

The global fight against the COVID-19 pandemic has underscored the critical importance of widespread vaccination to mitigate the impact of the virus on public health. The current study aimed to investigate which social influences might be most important for predicting attitudes towards COVID-19 vaccination and vaccine uptake among young students in the UK. We focused on the cultural evolution and social transmission aspects, i.e., parent-to-child versus peer-to-peer, of attitudes and vaccine uptake during the COVID-19 pandemic. A sample of 192 UK students (aged 18 to 35 years old) filled in an online survey including measures for attitudes towards COVID-19 vaccination and vaccine uptake and/or intention, age, and gender. Participants were also asked about their mother's, father's, and best friend's attitudes towards COVID-19 vaccination and vaccine uptake. Finally, they provided a subjective measure of the quality relationship with their parents. Overall, our results suggest that both parents and very close friends are important agents in understanding the students' attitudes towards COVID-19 vaccination and vaccine uptake. More specifically, our findings suggest the mother's vaccine uptake as the most salient predictor of students' attitudes towards COVID-19 vaccination and vaccine uptake, particularly when the students report having a positive relationship with their parents. In cases where students' experience negative relationship with their parents, the best friend's vaccine uptake may supersede the mother's influence. Despite these nuances, a general trend emerges from our data suggesting that vaccine uptake could be primarily guided by vertical transmission (i.e., parent to child). Our results have the potential to influence public health strategies, communication campaigns, and targeted interventions to enhance vaccination uptake. Identifying key social predictors can enable policymakers and health authorities to tailor vaccination promotion efforts towards mothers' and peers' vaccine uptake to increase overall positive attitudes and vaccine uptake among young people.

Pediatric thyroid cancer in Saudi Arabia: a literature review of current trends in management and outcomes.

Pediatric thyroid cancer is on the rise, especially among adolescents. It is more aggressive than adult thyroid cancer and often presents with advanced features. This review aims to examine the current trends in the management and outcomes of pediatric thyroid cancer in Saudi Arabia. A comprehensive literature search was conducted to identify relevant studies on pediatric thyroid cancer in Saudi Arabia. PubMed and Google Scholar were searched from inception until December 2023. Extracted information included study identifiers, patient demographics, clinicopathological features, treatment modalities, complications, surveillance practices, recurrence patterns, and survival outcomes. The literature search identified ten eligible studies on pediatric thyroid cancer in Saudi Arabia. Pediatric thyroid cancer in Saudi Arabia often presents with advanced features, including higher rates of lymph nodes and distant metastases at diagnosis compared to adults. Fine-needle aspiration remains accurate, correlating well with final histopathology. Treatment primarily involves surgery, with total thyroidectomy being common, followed by radioactive iodine therapy for high-risk patients or those with positive iodine uptake. Survival rates exceed 95%, indicating a generally favorable prognosis. Recurrence rates can reach up to 30% in some studies, particularly with larger tumors or distant metastases. Hypocalcemia and recurrent laryngeal nerve injury are common postoperative complications, highlighting the need for experienced surgeons and meticulous technique. Genetic alterations in pediatric thyroid cancer are being investigated, but their impact on prognosis and treatment response is unclear. Limited data on management and outcomes in other regions of Saudi Arabia calls for multicenter studies to address healthcare disparities. Pediatric thyroid cancer in Saudi Arabia has unique characteristics compared to its adult counterpart, mandating specialized management approaches. More research is needed on early detection, risk stratification, personalized treatment, and addressing regional disparities to improve outcomes for this vulnerable population.

Needs assessment and patient-guided development of a video-based diabetic retinopathy patient education tool

Objective: To gain retina physicians’ and diabetic retinopathy (DR) patients’ perspectives on needs and opportunities in DR education, and then develop and pilot test an educational video. Design: This study utilised qualitative interview data for video creation, and interview and survey data for assessment. Setting: This study was conducted in a single large academic medical centre. Method: We conducted semi-structured interviews with attending retina physicians and DR patients (Cohort A) which were coded for themes about needs in DR patient education. Using these interviews, we designed and piloted a 6-minute user-centred animated video among a second patient cohort (Cohort B), who completed post-intervention interviews. Results: Four physicians and 14 DR patients participated in the study. Themes from Cohort A included accessible information, early management, lifestyle factors and emotional context. Physician themes included effective communication, visual information delivery and individual-level diabetes management. Cohort B commented on the subsequently created video’s improved accessibility, engagement and supplementation of their existing DR knowledge. Conclusion: Physicians and patients showed an interest in video education and identified unique educational needs. We used these insights to create a video that demonstrated positive patient uptake. Close attention to retina physicians’ and DR patients’ perspectives can offer a valuable approach in developing materials to increase patients’ health knowledge. Within the context studied, videos may be more accessible and engaging than the use of traditional print-based education materials.

The added value of positron emission mammography in the assessment of the axillary lymph nodes of the pathologically proven breast cancer

BackgroundThe staging and management of patients with breast cancer are significantly influenced by the pathological state of the axillary lymph nodes (ALN). Thus, it is very desirable to have a differential diagnosis of metastatic ALN.PurposeThe aim of this research is to assess the effectiveness of non-invasive ALN staging using PEM versus traditional breast mammography and ultrasound in patients presenting with early-stage breast cancer. This study focuses on determining if PEM can reliably stage ALNs and potentially eliminate the need for more invasive methods.MethodsIn a study involving 94 breast cancer patients, PEM was used to assess ALNs. The nodes were visually evaluated for positive or negative uptake, and further categorized as non-specific, indeterminate, or malignant based on their maximum uptake values. This classification was then compared with histopathological results.ResultsThere were a total of 94 breast cancer patients; the results from PEM demonstrated an ALN detection sensitivity of 83.3%. The specificity of PEM in this context was found to be 98.08%, and the overall accuracy rate was 91.49%. Additionally, the Positive Predictive Value (PPV) was calculated to be 97.2%, and the Negative Predictive Value (NPV) was 87.9%.ConclusionsThe initial study has shown encouraging outcomes in terms of accurate lymph node assessment.

Assessment of incidental cardiac uptake in bone scintigraphy across Spain: The ECCINGO study

AimMyocardial uptake on bone scintigraphy has become useful for the detection of transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to assess the prevalence of myocardial uptake in patients over 18 years of age with no clinical suspicion of cardiac amyloidosis (CA) who had undergone bone scintigraphy. Methods and resultsThis was an observational, retrospective, multicenter study across 21 Spanish hospitals (September–November 2019). Of the 9864 scans analyzed (locally and centrally), incidental cardiac uptake was observed in 71 patients (0.72%), a prevalence that increased with age. A previous diagnosis of heart failure was found in 16.9% of patients with positive uptake, with >50% in NYHA II. ATTR-CA was diagnosed in 10 patients, with a mean delay of 10.4 months (95% CI: 5.1–15.7). All were >70 years old, primarily male, and had greater left ventricular hypertrophy than patients without a confirmed diagnosis (p<0.0001). ATTR-CA patients had higher rates of orthostatic hypotension (30.0% vs. 3.8% in non-ATTR-CA; p=0.025). ConclusionsThis is the first retrospective, national, multicenter study evaluating the prevalence of incidental cardiac uptake in bone scintigraphy performed for non-cardiac reasons, showing a prevalence of 0.72% in this population. Referral of these patients may facilitate early diagnosis of CA with a resulting benefit for patients.

Fine needle aspiration diagnosis of benign oncocytic lesions of the head and neck associated with false positive 18F-fluorodeoxyglucose uptake on positron emission tomography scan.

18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) has become the mainstay for staging and post-therapy surveillance of cancer as malignant neoplasms generally demonstrate higher FDG uptake that benign entities. However, there are certain benign lesions, most notably oncocytic tumors, that can display very high uptake and fine needle aspiration (FNA) is usually done to confirm malignancy. Therefore, it is important to recognize that benign oncocytic lesions of the head and neck may also present as FDG-avid lesions to avoid a diagnostic pitfall. Electronic search of institutional surgical and cytopathology archives was conducted to identify cases of benign oncocytic lesions involving the head and neck region diagnosed by FNA from January 2012 to April 2022. Chart review was used to assess whether lesions were initially discovered via PET scanning. One hundred and twenty-five cases of oncocytic lesions were identified; 12 (9%) PET positive lesions were identified in the head and neck region from patients being evaluated for metastasis or for suspicion of malignancy. Cytopathology of all 12 cases demonstrated benign oncocytic lesions; eight (67%) of these cases were consistent with Warthin tumor, one (8.3%) was a benign oncocytic lesion, and one (8.3%) was consistent wit a parathyroid adenoma. Most (58%) of the PET-positive lesions were in parotid region, two from thyroid gland (17%), one from submandibular gland (8%), one from paratracheal area (8%). The PET scan SUVs ranged from 3.3 to 19.5 g mL-1. Oncocytic lesions including Warthin tumors can result in false-positive FDG uptake on PET scans. Clinicians and cytopathologists should be aware of PET-positive benign oncocytic head and neck lesions.

18F]FDG PET/CT in Benign and Malignant Diseases Involving the Biliary Tract.

Role of FDG PET/CT in evaluation of biliary tract diseases remains relatively unexplored. PET/CT with FDG helps in evaluation of both infective / inflammatory as well as neoplastic diseases as increased glucose utilization is observed in both the conditions. In this article, we describe the spectrum of FDG PET/CT findings in various diseases affecting the biliary tract. Role of FDG PET/CT in neoplastic diseases involving the biliary duct has been described at the time of staging and response evaluation; in characterization of the intrahepatic mass (abscess v/s cholangiocarcinoma). In addition, we have discussed about the false positive FDG uptake along the biliary duct stent, which interfere with scan interpretation. Few of the benign conditions described are Langerhans cell histiocytosis and IgG4 related disease involving the biliary duct and adenomyomatosis and Xanthogranulomatous cholecystitis involving the gall bladder.

Single-Photon Emission Computed Tomography (SPECT-CT) as a Predictor of Pain Generators in Patients Undergoing Anterior Cervical Discectomy and Fusion (ACDF) for Axial Cervical Pain.

Axial neck pain is often associated with cervical instability, and surgical options are oftenreserved for patients with either neurological compromise or deformity of the spine. However, cervical facet arthropathy is often implicated with instability and the location of painful generators is often difficult to ascertain. Single-photon emission computed tomography (SPECT-CT) presents an adjunct to conventional imaging in the workup of patients with suspected facetogenic pain. We aimed to report our experience with patients undergoing anterior cervical discectomy and fusion (ACDF) guided by SPECT-CT for axial cervical pain. We retrospectively identified all cases undergoing ACDF that presented with axial neck pain where correlating SPECT-CT high metabolism areas were identified. Patientswere treated at a tertiary care institution between January 2018 and January 2021. Patients with positive radiotracer uptake pre-operatively were compared with patients undergoing ACDF without uptake on SPECT-CT. The pre- and post-operative patients who reported neck pain at one year were compared. Thirty-fivepatients were included in this retrospective cohort.The median pre- and post-intervention (at one-year follow-up) visual analog score (VAS) of patients undergoing ACDF without uptake on SPECT-CT was 7 and 3 (p<0.01), while the pre- and post-VASfor patients undergoing surgery with positive uptake on SPECT-CT was 8.5 and 0 (p<0.01).Improvement was significantly larger for patients undergoing SPECT-CT-guided ACDF (p=0.02). At one year after surgery, none of the assessed patients required additional surgical intervention. This case series represents the experience of our group to date with patients undergoing SPECT-CT-guided ACDF with results suggesting potential benefit in guiding fusion.

Baseline knowledge on risk factors, symptoms and intended behavior of women and men towards screening and treatment of cervical cancer in rural Uganda: a cross-sectional study

BackgroundKnowledge of risk factors and symptoms of cervical cancer has been found to promote uptake of screening of cervical cancer. Most interventions targeted women without much involvement of men (husbands/decision makers) who are often decision makers in many low- and middle-income countries. This study aimed at assessing baseline knowledge and intended behavior of both women and men to enable design specific targeted messages to increase uptake of cervical cancer screening and promote early detection of women with symptoms.MethodsThis cross-sectional study was conducted in two districts in Western Uganda using the modified African Women Awareness of CANcer (AWACAN) questionnaire. Women aged 30—49 years and their husbands/decision makers were interviewed. Knowledge on risk factors and symptoms, intended behavior and barriers towards participation in cervical cancer screening and treatment were assessed. Descriptive and logistic regression analyses were done to establish the association between knowledge levels and other factors comparing women to men.ResultsA total of 724 women and 692 men were enrolled. Of these, 71.0% women and 67.2% men had ever heard of cervical cancer and 8.8% women had ever been screened. Knowledge of risk factors and symptoms of cervical cancer was high and similar for both women and men.Lack of decision making by women was associated with low knowledge of risk factors (X2 = 14.542; p = 0.01), low education (X2 = 36.05, p < 0.01) and older age (X2 = 17.33, p < 0.01). Men had better help seeking behavior than women (X2 = 64.96, p < 0.01, OR = 0.39, 95% CI: 0.31—0.50) and were more confident and skilled in recognising a sign or symptom of cervical cancer (X2 = 27.28, p < 0.01, OR = 0.52, CI (0.40—0.67).ConclusionThe baseline knowledge for cervical cancer was high in majority of participants and similar in both women and men. Their intended behavior towards screening was also positive but screening uptake was very low. This study suggests developing messages on multiple interventions to promote screening behavior in addition to education, consisting of male involvement, women empowerment and making services available, accessible and women friendly.

Peptide-Driven Proton Sponge Nano-Assembly for Imaging and Triggering Lysosome-Regulated Immunogenic Cancer Cell Death.

Triggering lysosome-regulated immunogenic cell death (ICD, e.g., pyroptosis and necroptosis) with nanomedicines is an emerging approach for turning an "immune-cold" tumor "hot"-a key challenge faced by cancer immunotherapies. Proton sponge such as high-molecular-weight branched polyethylenimine (PEI) is excellent at rupturing lysosomes, but its therapeutic application is hindered by uncontrollable toxicity due to fixed charge density and poor understanding of resulted cell death mechanism. Here, a series of proton sponge nano-assemblies (PSNAs) with self-assembly controllable surface charge density and cell cytotoxicity are created. Such PSNAs are constructed via low-molecular-weight branched PEI covalently bound to self-assembling peptides carrying tetraphenylethene pyridinium (PyTPE, an aggregation-induced emission-based luminogen). Assembly of PEI assisted by the self-assembling peptide-PyTPE leads to enhanced surface positive charges and cell cytotoxicity of PSNA. The self-assembly tendency of PSNAs is further optimized by tuning hydrophilic and hydrophobic components within the peptide, thus resulting in the PSNA with the highest fluorescence, positive surface charge density, cell uptake, and cancer cell cytotoxicity. Systematic cell death mechanistic studies reveal that the lysosome rupturing-regulated pyroptosis and necroptosis are at least two causes of cell death. Tumor cells undergoing PSNA-triggered ICD activate immune cells, suggesting the great potential of PSNAs to trigger anticancer immunity.

Identifying Functional Lymph Nodes in Lower Extremity Lymphedema Patients: The Role of High-frequency Ultrasound.

Lymph nodes may play a potential role in lymphedema surgery. Radiologic evaluation of nodes may reveal the status of pathologic conditions but with limited accuracy. This study is the first to evaluate the efficacy of ultrasound in detecting functioning nodes in lymphedema patients and presents a criterion for determining the functionality of the lymph nodes. This retrospective study reviews 30 lower extremity lymphedema cases which were candidates for lymph node to vein anastomosis. Lymphoscintigraphy and magnetic resonant lymphangiography (MRL) imaging were compared with ultrasound features which were correlated to intraoperative indocyanine green (ICG) nodal uptake as an indication of functionality. Majority were International Society of Lymphology stage 2 late (50.0%) and stage 3 (26.7%). ICG positive uptake (functioning nodes) was noted in 22 (73.3%), while 8 patients (26.6%) had negative uptake (nonfunctioning). Ultrasound had significantly the highest specificity (100%) for identifying functional nodes followed by lymphoscintigraphy (55%) and MRL (36%; p = 0.002, p < 0.001, respectively). This was associated with 100% positive predictive value compared against lymphoscintigraphy (44%) and MRL (36%; p < 0.001 for both). The identified ultrasound imaging criteria for functioning lymph node were oval lymph node shape (Solbiati Index), morphology, vascularity pattern, and vascularity quantification. The use of ultrasound in nodal evaluation was proven effective in different pathologic conditions and demonstrated the best prediction for functionality of the lymph node based on the new evaluation criteria.

Abstract B043: Radiolabelled Trastuzumab Fab as a theranostic agent for HER2 expressing breast cancer

Abstract Breast cancer is the most common cause of mortality among women worldwide. Among all subtypes, HER2-positive breast cancers are highly aggressive and have poor prognosis. Surgical resection is choice of treatment. However, surgery may not be possible if disease is widespread. Trastuzumab, a monoclonal antibody, is globally used for immunotherapy. It is a large sized molecule (141kDa) and show slow pharmacokinetics and high liver uptake. We have explored trastuzumab fragment as a radio-theranostic agent. Trastuzumab Fab was generated using Papain enzyme tagged beads, incubation time 18 to 20 h at 850 rpm in phosphate buffer. Fab were collected with ultrafiltration device, cut off 30 kDa, in phosphate buffer pH 8. Quantification of Fab was done at 280 nm. Fab characterization was done using MALDI-TOF and SDS-PAGE. To enable radiolabelling of Fab with Ga-68 and Lu-177, Fab was conjugated with bifunctional chelator, DTPA. Fab-DTPA was separated by micro bio-spin P-6 chromatography columns and the average number of DTPA/Fab were calculated. Affinity of Fab conjugated Fab-DTPA for HER2 receptors was studied using the biolayer interferometry technique (BLI). Radiolabelling of Fab with Ga-68 for PET imaging and Lu-177 for therapy was optimized. Quality control included radiochemical purity using TLC in sodium citrate (pH 5) mobile phase, pyrogenicity using PTS, and sterility by tryptic soy broth culture media. Receptor affinity and apoptosis were studied with HER2 positive SKBR-3 cells using flow cytometry assay. The SKBR-3 cell (106) were cultured in 96 well plates and incubated with a known amount of Lu-177-DTPA-Fab (0- 18.5 MBq). First in human Ga-68 Fab PET/CT and Lu-177-Fab gamma camera images were acquired after obtaining clearance from Institutional Ethics Committee and inform signed consent. Patients were recruited with histopathological proven HER2 positive breast cancer and uptake on F-18 FDG PET/CT. Ga-68-DTPA-Fab (3.5-5 mCi) and 10-15 mCi Lu-177 DTPA-Fab was injected and images were acquired at 2/3 h and up to 7 days respectively. Dominant Fab peak at 45kDa on MALD-TOF, single band on SDS-PAGE (Non-reduced or reduced) have been obtained. Two DTPA/Fab were conjugated and confirmed by MALDI-TOF. BLI data showed Kd value of trastuzumab, Fab, and conjugated DTPA-Fab as 0.2 nM, 0.57 nM, and 20 nM for HER2. High labelling efficiency (≥98%) of Lu-177-DTPA-Fab and Ga-68-DTPA-Fab was achieved. Apoptosis (%) was 1.5%- 42.5% in SKBR-3 cells treated with Lu-177-DTPA-Fab. Both formulations were found sterile and pyrogen-free. Kidney and bladder activity of Ga-68/Lu-177-DTPA-Fab demonstrate renal clearance. Blood pool activity of both tracers were high. However, it was decreased, and lesion uptake was increased with time. All the lesions on Ga-68-DTPA-Fab, same as in F-18 FDG PET/CT, were picked up accept those near heart. Good lesion retention of Lu-177-DTPA-Fab was observed showing suitability for therapy. Fab-DTPA has potential to target HER2 receptor. It could be radiolabelled with Ga-68 for PET imaging and Lu-177 for targeted therapy. Citation Format: Jaya Shukla, Yogesh Rathore, Komalpreet Kaur, Santosh Irrinky, Rajender Kumar, Amanjit Bal, Bhagwant R Mittal. Radiolabelled Trastuzumab Fab as a theranostic agent for HER2 expressing breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B043.

Utility of positron emission tomography as a new tool for muscle involvement in patients with idiopathic inflammatory myositis: a controlled study.

Idiopathic inflammatory myositis (IIM) represents a rare group of disease that can affect multiple organs in addition to the muscles. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is an emerging scanning method that is widely used in diagnosing, staging and response to treatment in patients with cancer. In this study, we aimed to evaluate the muscle involvement in PET/CT which was performed for malignancy screening and its correlation with myositis-specific antibodies (MSA) and/or myositis-associated antibodies (MAA) in patients with IIM. IIM patients who fulfilled 2017 EULAR/ACR classification criteria and had PET-CT scans during the active phase of myositis (within two weeks of starting steroids) were included into the study. Age and sex matched participants with history of malignancy (non-IIM patients) were defined as control group. Data of 160 IIM patients were evaluated and 34 patients (of 64.7% female) whose PET/CT results were available, included into the study. Fourteen patients with diagnosis of malignancy without IIM (non-IIM patients) defined as the control group. Sensitivity and specificity of a positive FDG muscle uptake were 37.1% and 100%, 65.7% and 92.9%, 91.4% and 7.1% compared to liver, mediastinum and LTM uptakes, respectively. In multivariate analysis, higher baseline CRP (p=0.017, confidence interval [CI] 95%: 1.03-1.36, OR:1.18) and LDH (p=0.029, CI 95%:1.001-1.017, OR:1.01) levels were associated with muscle PET/CT positivity. In patients with active IIM, median muscle FDG uptake with PET/CT was higher compared to non-IIM. PET/CT may be used for the evaluation of extent and activity in patients with IIM.

The Lived Experiences of Pregnant and Parenting Women in Recovery Toward Medication Treatment for Opioid Use Disorder.

Maternal misuse of prescription opioids and illicit drugs such as, heroin and non-pharmaceutical fentanyl analogs has increased in the last 2 decades and one in 5 women reported misuse of opioids. Medications for opioid use disorder (MOUD) are recommended for treating pregnant women with opioid use disorder (OUD). MOUD is effective in reducing cravings and negative outcomes, yet treatment is underutilized and varies in integration and intensity of resources across health systems. Exploring perceptions of MOUD delivery among pregnant/parenting women promises to uncover and address the underlying challenges to treatment, a perspective that may be different for providers and stakeholders. Therefore, our main purpose is to elicit patients' experiences and perceptions of MOUD, associated access to treatment, and availability of supportive resources during pregnancy/postpartum to inform OUD treatment. Through a qualitative research approach we gathered data from individual interviews/focus group discussions for this pilot study. Pregnant and postpartum parenting women (n = 17) responded to questions related to perceptions of MOUD, access to treatment, and availability of social and psychosocial resources. Data were collected, transcribed, and coded (by consensus) and emerging themes were analyzed using grounded theory methodology. Emerging themes revealed positive uptake and perceptions of MOUD, continuing gaps in knowledge, negative impact of stigmatization, and limited access to programs and resources. Supportive relationships from family, peers, healthcare providers and child welfare staff, and co-located services were perceived as positive motivators to recovery. Through the unique lenses of women with lived experience, this study revealed several themes that can be transformative for women. Overall perceptions of MOUD were positive and likely to facilitate uptake and promote positive recovery outcomes. Bridging knowledge gaps will reduce anxieties, fears about neonatal opioid withdrawal syndrome and adverse maternal outcomes. Additionally, a deeper understanding of stigmatization and relationships can inform an integrated patient-centered approach to OUD treatment.