Personal History Research Articles

Germline pathogenic variants in a cohort of individuals with biliary tract cancer.

559 Background: Biliary tract cancers (BTC) are rare but have been implicated in hereditary cancer conditions such as Lynch syndrome (LS) and BRCA1 and BRCA2. Data from paired somatic and germline genetic testing on BTC have shown that ~5% may be related to germline pathogenic variants in BRCA1 and BRCA2. Identification of these germline pathogenic variants (PV) often provide patients with an opportunity for personalized treatment including platinum-based chemotherapies, PARP inhibitors and/or immunotherapy. Germline testing also provides crucial data to relatives regarding cancer risk and access to increased cancer surveillance and risk-reducing surgeries. Current guidelines recommend germline genetic testing when the likelihood of identifying a PV is >5%. The contribution of germline PV in BTC has not been described in a diverse patient population. Methods: In this prospective clinic-based study, individuals with BTC were referred by their oncologist for genetic counselling and testing. The majority of individuals were enrolled based on participation in the Legresley Biliary Registry, which recruits all individuals with BTC. Blood was sent for germline multi-gene panel testing. Results: Germline genetic testing was performed for 139 individuals. Average age of diagnosis was 57.8 years (range 28-84). The majority of individuals were diagnosed with intrahepatic cholangiocarcinoma (CCA) (54.7%), followed by extrahepatic CCA (20.9%) and gallbladder cancer (10.1%). The majority of individuals were male (56.1%). The population was ethnically diverse with 55% European, 24% Asian, 9% Middle Eastern/North African and 6% African. A minority of individuals had a previous cancer (18%) and 24.5% met current provincial eligibility criteria. Germline testing was complete on 136 individuals. 25/136 (14.7%) PV were identified in 20 individuals. 8/136 (5.9%) of the cohort carried PV in genes known to increase the risk for BTC ( BRCA1, BRCA2 and LS genes), 9/136 (6.6%) carried PV in other genes with clinically actionability (e.g. PALB2, ATM ), and 8/136 (5.9%) carried heterozygous PV in genes for recessive diseases. Variants of uncertain significance were identified in 42/136 (30.9%) and negative results were identified in 74/136 (54.4%). Personal and/or family history was not suggestive of the associated cancer condition in 9/16 (56%) of the PV cohort. Tumor profiling by whole genome sequencing on some individuals with PV found corresponding somatic mutational signatures, consistent with variant pathogenicity. Conclusions: Detection rates for PV in a diverse BTC cohort was up to 14.7%, including 5.9% among genes known to increase the risk for BTC. The majority of PV were found in individuals lacking personal and/or family history suggestive of the associated hereditary cancer condition. These results suggest that guidelines should be updated to recommend universal germline genetic testing for individuals with BTC.

Additive Value of Polygenic Risk Score to Family History for Type 2 Diabetes Prediction: Results From the All of Us Research Database.

The goal of this study was to assess the additive value of considering type 2 diabetes (T2D) polygenic risk score (PRS) in addition to family history for T2D prediction. Data were obtained from the All of Us (AoU) research database. First-degree T2D family history was self-reported on the personal family history health questionnaire. A PRS was constructed from 1,289 variants identified from a large multiancestry genome-wide association study meta-analysis for T2D. Logistic regression models were run to generate odds ratios (ORs) and 95% CIs for T2D. All models were adjusted for age, sex, and BMI. A total of 109,958 AoU research participants were included in the analysis. The odds of T2D increased with 1 SD PRS (OR 1.75; 95% CI 1.71-1.79) and positive T2D family history (OR 2.32; 95% CI 2.20-2.43). In the joint model, both 1 SD PRS (OR 1.69; 95% CI 1.65-1.72) and family history (OR 2.06; 95% CI 1.98-2.15) were significantly associated with T2D, although the ORs were slightly attenuated. Predictive models that included both the PRS and family history (area under the curve [AUC] 0.794) performed better than models including only family history (AUC 0.763) or the PRS (AUC 0.785). In predicting T2D, inclusion of a T2D PRS in addition to family history of T2D (first-degree relatives) added statistical value. Further study is needed to determine whether consideration of both family history and a PRS would be useful for clinical T2D prediction.

Randomized study to assess colonic microbiome changes in response to energy drink consumption (ROSANNA Trial).

TPS325 Background: Colorectal cancer (CRC), the second leading cause of cancer deaths in the US, is increasingly diagnosed in individuals under 50. This rise in early-onset CRC (eoCRC) led the U.S. Preventative Services Task Force to recommend a reduction in the age to begin colorectal cancer screening in average-risk persons, from 50 to 45. The etiology of eoCRC is multifaceted, with one postulated theory pointing to alterations in the young adult colonic microbiome. Hydrogen sulfide (H 2 S) producing bacteria, like Bilophila wadsworthia , Fusobacterium nucleatum and Atopobium parvulum , are typically minor gut microbiota components but are overrepresented in CRC cases, linked to inflammation, and may promote a pro-carcinogenic environment. These bacteria preferentially use taurine, an essential amino acid, as a primary energy source. Energy drinks represent one of the largest dietary sources (6-16x normal daily intake) of taurine in contemporary diets. Our hypothesis is that high taurine levels in energy drinks could exacerbate CRC risk by promoting preferential growth and metabolic activities of already present H 2 S-producing bacteria, contributing to the rise of eoCRC. Methods: This randomized open-label trial is actively enrolling up to 60 young adults (18-40 years) without personal or family history of CRC, other major GI disease/distress, and baseline infrequent energy drink consumption. Group 1 (Arm A; n=30), will consist of subjects consuming at least one of two protocol-specified energy drinks daily for 4 weeks. Group 2 (Arm B; n=30), will consist of usual dietary intake. Enrollments are randomized 1:1 and stratified, by gender, age (18-25 vs. 26-40), and baseline energy drink consumption (rare/none vs. 1-2 per week). Every subject will complete: 1) a daily dietary and fitness log, 2) a weekly wellness log, 3) collection of stool/saliva/skin/urine at 3 sequential time points (baseline, after 2 weeks, after 4 weeks), and 4) blood collection at the same time points. The primary endpoint is the change in H 2 S-metabolizing bacterial communities between baseline and 1 month of energy drink exposure within Arm A and also compared to those in Arm B using microbiome analysis (diversity, taxonomy, sulfur-enriched gene pathways). Several secondary and exploratory assessments include changes related to subject demographic and dietary differences, concordance of microbiome changes with dietary logs and in other biospecimens beyond stool, H 2 S-production measurements, and analyses of subject metabolic and immune function. Trial opened in February 2024 with active enrollment ongoing. Updated data on trial status and any amendment modifications will be presented at the meeting. Clinical trial information: NCT06137248 .

Effectiveness of the Colorectal Cancer Alliance's digital screening quiz and navigation model for promoting CRC screening.

97 Background: Evaluating the effectiveness of a Colorectal Cancer screening navigation model delivered in a digital platform offered by a patient advocacy organization. Designed as a digital screening quiz tool and live navigation to promote CRC screening, the Colorectal Cancer Alliance’s Screening Quiz is a risk stratification tool that connects respondents to live certified cancer care navigators delivering evidence-based interventions to increase CRC screening, education and patient and family support. The framework utilizes small and mass media, one-on-one education and patient navigation services to help address and reduce barriers to care. Research on these critical interventions shows that on-time screening for CRC leads to better outcomes. Methods: The Screening Quiz has been promoted through social sharing, community outreach, and media, including influencer campaigns to increase outreach to at-risk communities. Questions assess personal and family history, hereditary syndromes, and demographics to provide a CRC screening recommendation based on current USPSTF guidelines. Respondents overdue for screening are triaged to the Alliance’s patient navigation team. This interaction includes phone calls and emails for symptomatic individuals/high risk for CRC, telephone and email for average-risk uninsured, and emails for average-risk insured. At-risk individuals are connected to resources, such as financial assistance, free at-home screening tests, and colonoscopy scheduling services. Results: July 2022 to July 2024, the Screening Quiz provided over 50,000 screening recommendations. The median age of respondents was 46; 32% of respondents were between the ages of 45 to 64. Of the respondents, 29% were male and 71% were female. Most were White (79.2%), but nearly half of those who opted into navigation identified as BIPOC, including 16.7% Black/AA, 6.6% Asian, and 2.1% AI/AN. Additionally, 8.4% of respondents identified as ethnically Hispanic/Latino with another race. Most respondents were symptomatic (66.6%) but 6.5% were asymptomatic high-risk. These two groups represented 88% of 1,869 respondents triaged to patient navigation. Conclusions: The digital Screening Quiz, combined with live navigation, represents a promising approach for increasing CRC screening rates and addressing care gaps compared to traditional methods. The Alliance’s ability to engage at-risk communities through its national network of volunteers and partners, combined with evidence-based interventions, positions it well to continue closing screening gaps. Going forward, the Alliance aims to leverage its relationships with healthcare providers and community organizations further to expand the reach of its CRC screening efforts.

False-Negative Review from the Mammography Audit: Refining Breast Imaging Practice.

Annual review of false-negative (FN) mammograms is a mandatory and critical component of the Mammography Quality Standards Act (MQSA) annual mammography audit. FN review can help hone reading skills and improve the ability to detect cancers at mammography. Subtle architectural distortion, asymmetries (seen only on one view), small lesions, lesions with probably benign appearance (circumscribed regular borders), isolated microcalcifications, and skin thickening are the most common mammographic findings when the malignancy is visible at retrospective review of FN mammograms. Most FN mammograms are not due to radiologist error. There are common and predictable settings in which FN mammograms occur. Patient factors associated with elevated FN mammograms include dense breasts, elevated lifetime risk of breast cancer, and personal history of breast cancer treated with lumpectomy and radiation therapy. About half of FN cancers are detected by supplemental screening examinations and half manifest clinically. The most common manifesting symptoms for interval cancers are a palpable abnormality, nipple discharge, and skin changes. Interval cancers can have more aggressive pathologic features and higher rates of node positivity. The FN review includes Breast Imaging Reporting and Data System (BI-RADS) 3 cases that develop a cancer diagnosis during surveillance. Nonbreast malignancies diagnosed as interval cancers (most commonly lymphoma and metastatic disease) do not need to be counted as FNs for audit purposes. The FN review and annual audit are confidential processes that protect patient and radiologist information while allowing meaningful quality control and improvement. Although FN mammograms are rare, review of these cases is a valuable educational tool. The slide presentation from the RSNA Annual Meeting is available for this article. ©RSNA, 2025.

Outcomes of surveillance in patients with intraductal papillary mucinous neoplasms (IPMNs) who tested negative for high-risk mutations (HRMs) in next-generation sequencing (NGS).

704 Background: HRMs in NGS have demonstrated high sensitivity and specificity for predicting advanced neoplasia in patients with IPMNs. However, the outcomes of surveillance in patients who tested negative for these HRMs have not been investigated in prior studies. This study aimed to identify the predictors of progression in patients with negative NGS results for HRMs. Methods: We conducted a retrospective review of prospectively collected data from patients who underwent NGS testing between 2016 and 2023 in our pancreatic cancer prevention program. Patients without IPMNs (i.e., negative for KRAS/GNAS), with HRMs, and those without at least one follow-up imaging post-NGS were excluded from the study. Progression was defined as the development of new or additional worrisome features or high-risk stigmata (per Kyoto guidelines), or advanced neoplasia (HGD/PDAC) following NGS testing. A Cox proportional hazards regression model was used to identify predictors of progression. Results: A total of 543 patients underwent NGS testing during the study period, of which 210 patients met the inclusion criteria. The median follow-up duration was 22 months (IQR = 12-36). Of these, 72 patients developed progression following NGS testing. A total of 11 patients underwent surgical resection, and 5 of them had HGD. Factors predictive of progression included a history of smoking (HR = 1.74; 95% CI = 1.06 - 2.86), larger cyst size (HR = 1.09; 95% CI = 1.03 - 1.16), and the presence of a dilated main pancreatic duct (MPD) (HR = 2.56; 95% CI = 1.5 - 4.4) prior to NGS testing. The median time to progression for patients with worrisome features was 33 months, compared to 59 months for those without worrisome features at baseline. Similarly, the median time to progression for patients with cysts ≥ 2 cm was 38 months, compared to 57 months for those with cysts < 2 cm. Conclusions: Patients who test negative for high-risk mutations in NGS are not exempt from the risk of progression. Any smoking history and presence of any worrisome features before NGS testing showed to be independent predictors of disease progression. For patients with smoking history, worrisome features or cysts ≥ 2 cm, frequent surveillance should be recommended following NGS testing. Results of Cox proportional hazards regression model for identifying the predictors of progression. Variables Hazards ratio (HR) 95% Confidence Interval P-value Age 0.99 0.96 – 1.01 0.257 Male sex 1.02 0.62 – 1.7 0.93 White race 1.07 0.63 – 0.83 0.8 Family history of pancreatic cancer 0.6 0.26 – 1.36 0.22 Personal history of other cancers 0.95 0.56 – 1.62 0.86 Diabetes 1.22 0.72 – 2.05 0.46 Any history of smoking 1.74 1.06 – 2.86 0.03* Pre-NGS cyst size (cm) 1.09 1.03 – 1.16 0.006* Pre-NGS dilated main pancreatic duct (≥5mm) 2.56 1.5 – 4.4 0.001* Pre-NGS presence of mural nodules 0.32 0.04 – 2.37 0.26 *Significant p-value.

Independent risk factors for twin pregnancy adverse fetal outcomes before 28 gestational week by first trimester ultrasound screening.

The incidence of multiple pregnancies has increased worldwide recently and women with a twin pregnancy are at higher risk of adverse outcomes compared with women with a singleton pregnancy. It is important to understand the risk factors for adverse fetal outcomes in twin pregnancy in order to guide clinical management. To identify the independent risk factors, including maternal personal and family medical histories and first trimester ultrasound screening findings, for adverse fetal outcomes of twin pregnancy before 28 weeks of gestation. The data of 126 twin pregnancies in our hospital, including pregnancy outcomes, first trimester ultrasound screening findings and maternal medical history, were retrospectively collected. Twenty-nine women with adverse outcomes were included in the abnormal group and the remaining 97 women were included in the control group. Patients in the abnormal group were more likely to be monochorionic diamniotic (13/29 vs 20/97, P= 0.009), with a higher mean pulsatility index (PI, 1.57 ± 0.55 vs 1.28 ± 0.42, P = 0.003; cutoff value: 1.393) or a higher mean resistance index (0.71 ± 0.11 vs 0.65 ± 0.11, P = 0.008; cutoff value: 0.683) or early diastolic notch of bilateral uterine arteries (UtAs, 10/29 vs 15/97, P = 0.024) or with abnormal ultrasound findings (13/29 vs 2/97, P < 0.001), compared with the control group. Monochorionic diamnioticity, higher mean PI of bilateral UtAs and abnormal ultrasound findings during first trimester screening were independent risk factors for adverse fetal outcomes (P < 0.05). First trimester ultrasound screening for twin pregnancy identifies independent risk factors and is useful for the prediction of fetal outcomes.

Markers for Pressure Injury Risk in Individuals with Chronic Spinal Cord Injury: A Pilot Study.

To identify markers associated with pressure injury (PrI) history in individuals with spinal cord injury (SCI) using two approaches: skin blood flow (SBF) response toward localized heating, and serum marker for insulin resistance. For this cross-sectional, observational study of adults with chronic traumatic SCI at T12 and above, researchers recruited two groups of participants: with history of PrI (group 1), and without history of PrI (group 2). The study protocol included obtaining fasting blood samples and measurement of SBF at bilateral heels with localized heating of 42 °C for 30 minutes from all participants. Primary SBF outcomes were initial peak and plateau SBF normalized to baseline SBF. The primary outcome for insulin resistance was Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), calculated from fasting plasma glucose and insulin. Secondary outcomes included demographic and SCI information. Researchers used the Fisher exact test and Wilcoxon-Mann-Whitney test to compare the intergroup difference of categorical and continuous variables, respectively. Sixteen adults completed this study (group 1, n = 7; group 2, n = 9). In comparison with group 2, group 1 had significantly higher HOMA-IR (3.90 ± 0.71 vs 1.45 ± 0.71), suggesting higher insulin resistance, and longer duration of injury (22.54 ± 7.24 vs 7.98 ± 6.58 years). There were no between-group differences in SBF or other secondary outcomes. HOMA-IR is a novel serum index associated with PrI history in persons with chronic SCI. Future longitudinal study is warranted to examine the role of insulin resistance in increasing PrI risk for the SCI population.

Role of interleukin-4 receptor α polymorphism in patients with asthma and its correlation with asthma severity

Asthma is a heterogeneous disease characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and intensity, together with variable expiratory airflow limitation. A personal history or a family history of allergy is the factor most strongly associated with the development of asthma. Our primary aim was to investigate interleukin-4 receptor α (IL-4Rα) polymorphism to determine whether the presence of the R576 IL-4Rα allele was associated with asthma and whether the presence of the R576 allele influenced the severity of asthma in affected individuals. The data obtained indicated asthmatic patients were characterized by a higher prevalence of positive family history of asthma (p&lt;0.001) as compared to controls. It was found that the patients homozygous for mutant alleles had a 1.39-fold increased risk of asthma compared with individuals not homozygous for R576. Also, we found that females had higher odds (1.61-fold) of significant association with asthma (p=0.09; odds ratio=1.58). While this report clearly necessitates a more detailed study, it is plausible that IL-4 mutation has a significant role in the development of asthma and, thus, can play an important role in developing targeted therapy.

O-16 A CASE OF VITAMIN D-DEPENDENT RICKETS DIAGNOSED IN ADULTHOOD FOLLOWING PREGNANCY

Abstract Discussion Vitamin-D (Vit-D)-dependent rickets are the result of a deficiency in 1-alpha hydroxylase. It is a rare condition that is typically diagnosed in childhood. We present a case of Vit-D-dependent rickets that was detected in adulthood after pregnancy. Clinical Case A 25-year-old female patient has been sent from the neurosurgical clinic to the endocrinology department for evaluation of Vit-D deficiency, which is believed to be causing muscle weakness. She experienced chronic lower back discomfort that began two years ago. She experienced challenges when going down stairs and when bending her body forward. Rest alleviated the lower back pain, whereas physical activity exacerbated it, and it did not interfere with her sleep. The weakness in the legs was there with it. There was no previous fractures or other form of physical injury. The woman's issues became evident after her pregnancy. She consulted a physician nine months postpartum, following the birth of a robust infant. The patient's personal and family history was unremarkable. She had no smoking or drinking habits. During the physical examination, the patient stood 150cm tall and weighed 60kg. Except for left lower extremity muscle strength, which was 3-4/5 on the neurological assessment, everything else was normal. In her laboratory results; calcium 8 mg/dl (8.8-10.6), ionized calcium 3.61mg/dL (4.6-5.0), albumin 4.7 g/dl (3.5-5.2), phosphorus 2.1 mg/dl (2.5-4.5), parathormone 640 ng/L (12-88), creatinine kinase 50 U/L (0-145), alkaline phosphatase 345 U/L (33-98), 25-OH Vit-D 24.2 ug/L, leukocyte: 7100/uL, hemoglobin 11.6 gr/dl, thrombocyte 336000/uL, ALT: 6.6 U/L, osteocalsin: 65 ng/mL (11-48), 1,25-OH Vit-D level: 43.1 pg/mL (15-90). Computed CT revealed type H vertebrae in the thoracic vertebrae, with no disease found in the lumbar, cervical, pelvic, or femur. (Figure 1). Bone density (BD): L1-L4 Z score: -2.7 BMD: 0.858; Femoral neck Z score: -2.7 BMD: 0.644. The EMG results were consistent with moderate myopathy. After one year of complaints, she became wheelchair-dependent. At that point, a neurosurgical doctor prescribed Vit-D and calcium tablets. She was able to walk again in two months and referred to our clinic two years after the initial issue. Genetic testing revealed that CYP27b1&amp;gt;homozygous positive was compatible with Vit-D dependent Rickets Type 1. During the two-year diagnostic period, the patient's height dropped from 153 cm to 150 cm. Calcitriol 0.25 mcg was administered every other day. Her calcium level: 9.4 mg/dL and phosphorus level: 2.2 mg/dL following treatment. This type of rickets is caused by a lack of the 1-alpha hydroxylase enzyme, which is essential for Vit-D production in the kidney. Untreated patients may have muscular and bone abnormalities. It is a sickness that responds exceptionally well to treatment.Figure 1:Vertebral lateral X -ray revealed H shaped vertebrae

O-08 AGGRESSIVE PARAGANGLIOMA-PHEOCHROMOCYTOMA: AN UNDER-TOLD STORY OF THE SDH-D MUTATION

Abstract Introduction Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are defined by the occurrence of paragangliomas derived from the autonomic nervous system and pheochromocytomas that are localized to the adrenal medulla. While pheochromocytomas and sympathetic paragangliomas cause catecholamine hypersecretion, parasympathetic paragangliomas are mostly nonsecretory. A diagnosis of hereditary PGL/PCC is based on a personal and family history of recurrent, multiple, early-onset PGL/PCC and the identification of mutations in the disease-related genes. Germline mutations in succinate dehydrogenase (SDH) genes are among the most common susceptibility genes. Some of these tumors, particularly those related to SDH-B, exhibit a significant malignant potential. However, mutations in the SDH-D gene do not often predispose to aggressive disease. Clinical Case A 24-year-old male patient presented to the outpatient clinic with a headache and right flank pain. There was not family history of the disease, except for the sudden death of his father at the age of 43. An MRI of the abdomen revealed a 45x44 mm lesion in the right adrenal gland. The patient's urinary normetanephrine levels were found to be significantly elevated. Subsequently, a right adrenalectomy was performed, and the pathology report confirmed a diagnosis of pheochromocytoma. The patient was referred to our clinic after 123 - Iodine MIBG SPECT/CT scan revealed the presence of a 24x15 mm lesion at the left cervical level 3 and a 21x35 mm lesion at the right paraaortic level. Concurrent plasma and urinary catecholamine levels were within the normal range. Both were surgically excised, and the pathology result was reported as paraganglioma. The molecular analysis revealed a pathogenic SDH-D gene variant:c.147dupA (p.His50fs).The patient was started to be monitored annually. In the third year of follow-up, a 14x12 mm nodular lesion was detected in the aorticopulmonary space. The lesion was not excised due to its proximity to vital structures and the patient was continued to be monitored. During the four-year period, there was not significant growth was observed in the lesion. However, in the fifth year detection of the lesion, it's size was reaching to 28x26 mm. It was excised via thoracic surgery. The pathology result was consistent with paraganglioma, with positive surgical margins and a Ki-67 index of 6%.Despite the recommendation for genetic screening, the patient's family members declined. Ten years after the initial diagnosis, the patient's cousin presented with cervical paraganglioma at the age of 19. Conclusion The presented case demonstrates the significance of molecular testing for patients with PGL/PCC and the necessity of long-term follow-up. Furthermore, it suggests that individuals carrying the SDH-D gene mutation may be at an increased risk of an aggressive disease course. Therefore, the precision of genetic counseling is of vital importance in establishing clinical screening and follow-up strategies.Figure 1:Transvers view of Chest CT showing paraganglioma located in aortopulmonary space. Table 1:Catecholamine metabolites in 24 hour urine at diagnosis

PRESERVACIÓN DEL MIEMBRO INFERIOR Y RECUPERACIÓN FUNCIONAL EN FRACTURA COMPLEJA DE CALCÁNEO: RELATO DE CASO EXITOSO CON LA UTILIZACIÓN DE LA TÉCNICA DE FIGUEIREDO

Calcaneal fractures, often the result of high-energy trauma such as falls from heights or automobile accidents, have an intricate anatomy that makes diagnosis and treatment difficult. Finding an effective technique to close skin lesions is a challenge for the surgeon community today. The Figueiredo technique offers an innovative and accessible approach to treating these conditions. By using the lesion cover with polypropylene prosthesis to protect surgical wounds, this methodology aims to create an environment conducive to healing while minimizing the risk of infection and complications. This low-cost procedure represents an alternative to conventional methods, paving the way for a faster and more effective recovery of patients. The case report is of a male patient, 60 years old, with no personal history of chronic diseases or relevant comorbidities, who goes to the emergency department for a motorcycle accident, presenting direct high energy trauma in the distal portion of the lower limb with extensive involvement of the limb, associated with significant postero-inferior displacement and exposure of the bone fragment, plus massive loss of substance in surrounding soft tissues greater than 10 centimeters in diameter. Following initial assessment and stabilization of the patient in the emergency room, his admission was planned with indication of transtibial amputation due to signs of suffering of soft parts (tissue damage), bone exposure and contamination at the site of the injury. However, once in the operating room, it was decided to modify the patient’s surgical plan, opting for the Figueiredo technique, being a conservative strategy with good potential for healing, prioritizing preserving the limb and the functionality of the member, given the general good condition of the patient, the considerable viability of surrounding tissues and appropriate vascular perfusion despite the degree of involvement and indication of amputation. Surgical cleansing is performed with thorough washing of the affected site with 9 liters of saline serum at 0.9%, extensive debridement of necrotic tissues, reduction and stabilization of the fracture by means of fixation with Kirschner threads. Subsequently, the affected part is covered with temporary polypropylene prosthesis, using the Figueiredo technique. The results obtained indicate that the Figueiredo technique, when well performed, with injury favorable to the technique, satisfactory performance of the application of the technique, and follow-up after surgery, was extremely effective, It is a more cost-effective technique for the patient and the hospital, and is also more likely to recover its specific tissue from the site of the injury.

This is not fiction: Russia and the Soviet Union in Finnish translated nonfiction in 2000–2023

ABSTRACT This study examined nonfiction literature on Russia or the Soviet Union, referred to as the ‘topic culture,’ published in Finland between 2000 and 2023. My aim was to provide a description of the characteristics of nonfiction literature on Russia or the Soviet Union published in Finnish during this period, to map the source languages and cultures of the publications, and to identify their topics and themes. An attempt was made to find links between the numbers and topics of translations and political events. The theoretical basis for this macro-level, mostly qualitative analysis is Toury's (1995/2012) concept of translation policy and attitudes toward indirect translation in the target culture. The topics and themes of the translated works were analyzed by examining the back cover texts or other descriptions of works available from the National Library of Finland and publishers’ websites. The study shows that a variety of topics and themes have been published, the most common being personal history, war history, and societal development. Russian was the most common source language at the beginning of the survey period but has been replaced by English as the dominant source language.

Rewriting (personal) history – portrayal of Emilio Aguinaldo and Booker T. Washington in adventure stories and articles in “Bōken Sekai” (The World of Adventure) magazine

Rewriting (personal) history – portrayal of Emilio Aguinaldo and Booker T. Washington in adventure stories and articles in “Bōken Sekai” (The World of Adventure) magazine

P0974 Risk factors for anti-TNFα induced paradoxical psoriasis in Inflammatory Bowel Disease and association with an IL-23 receptor polymorphism: A retrospective study

Abstract Background Anti-tumor necrosis factor (TNF)-α therapy is frequently used to treat inflammatory bowel disease (IBD). Paradoxical psoriasis (PP) is a known adverse effect of this drug class resulting in disfiguring skin lesions that may impact quality of life and lead to treatment cessation. To date, there are no tools to identify individuals who are susceptible to developing PP. Variations in the IL-23 receptor (IL23R) gene have been linked to psoriasis onset and may be implicated in PP. The aims of this study are 1. to study the incidence and outcomes of PP in anti-TNFα treated IBD patients at an academic centre in London, Ontario, Canada and 2. to examine risk factors associated with PP including the IL23R variant (IL23R1142G&amp;gt;A). Methods We performed a retrospective study of adult IBD patients treated with anti-TNFα therapies at London Health Sciences Centre between 2012 and 2024. Patient charts were reviewed for clinical variables and disease outcomes from the time of anti-TNFα exposure until treatment discontinuation or last follow-up. Patients’ serum was retrospectively genotyped for the IL23R1142G&amp;gt;A variant. Results We identified 496 IBD patients with 570 unique anti-TNFα exposures between 2012 and 2024. 26 patients developed 29 cases of PP while the remaining 473 patients did not develop PP after exposure to 542 anti-TNFα therapies, corresponding to a PP incidence rate of 5.1% in the study population. There was an increased proportion of patients with PP who had a positive family and personal history of psoriasis, though the latter was not significant (Table 1). The IL23R variant was more common in patients who developed PP compared to those who did not (46.2% vs. 5.1%, OR 16.04, 95% CI 6.69-38.41, Figure 1). The average time to develop PP was 9.5 months, with 55% of patients on high-dose anti-TNFα maintenance regimens. Majority of patients had moderate-to-severe disease (72.4%) based on body surface area (BSA) involvement and required treatment cessation (69.0%). All participants had complete resolution of PP following discontinuation of anti-TNFα therapy. Conclusion We identified an increased frequency of the IL23R1142G&amp;gt;A variant in patients who developed PP following anti-TNFα exposure compared to those who did not. Personal and family history of psoriasis were also more common in those who developed PP. Future studies should investigate other drug and disease characteristics that may predict those at highest risk for this anti-TNFα drug effect.

P0247 Clinical and Colonoscopic Features of Colitis in HIV-Positive Patients Mimicking Inflammatory Bowel Disease Over the Past 12 Years

Abstract Background Not only the incidence of inflammatory bowel disease(IBD) but also that of HIV-positive colitis is increasing as individual freedom is emphasized, making the diagnosis of IBD more challenging nowadays. Methods We reviewed the data of 75 HIV-positive patient at Daehang Hospital, Seoul, from January 2012 to October 2024. Ten patients were filtered from retrospective medical records analysis who were suspected to have IBD before the HIV-positive diagnosis. Results Among the 10 patients suspected to have IBD, all were men with a median age of 27, ranging from 22 to 62. Symptom complaints started 2 week ago(2 men), 1 month ago(6 men), 2months ago(1 man), 6month ago(1 man). Initial diagnoses from personal history were ulcerative colitis(5 men), Crohn’s disease(3 men), irritable bowel syndrome(1 man), infectious colitis(1 man). Anal sex history could be obtained from 5 patients. Colonoscopy revealed rectal ulcers(4 men), whole colon ulcers or erosions(4 men), left colon erythema, edema (1 man), and anal abscess(1 man). One patient was found to have amebiasis from cecum tissue. Conclusion HIV-positive colitis is very rare but now increasing, necessitating differential diagnosis. Initial suspicion through careful history taking and close observation of colonic mucosal lesions could reduce the misdiagnosis of IBD. Further large-scale cases are needed to identify the characteristics of HIV-positive colitis to exclude the diagnosis of IBD.

Sergey Alexandrovich Tokarev and the Intellectual Landscape of Soviet Yakutia: A Historical and Hermeneutic Reconstruction

This article is devoted to the Yakut period in the biography of the famous scientist S. A. Tokarev. The Archive of the Yakut Scientific Center of the Siberian Branch of the Russian Academy of Sciences contains a corpus of a few ego-documents related to the period of collaboration between Professor Sergei A. Tokarev and the Yakut Institute (1935-1959), the personal fund of the repressed ethnographer and orientalist Gavriil V. Ksenofontov and the historian Vasilii N. Chemezov. The study employs the methodology of “new biographical history” (social personal history), through which the formation of S. A. Tokarev’s individual scientific strategy during the period of early Soviet society’s construction is traced. The intellectual biography is reconstructed in the historical and hermeneutic space of the studied era, which allows the authors to reveal the social context of the historical narrative in which S. A. Tokarev’s scientific worldview was formed. The new interpretation of the scientists’ biography highlights the moment when the academic northern studies commenced in Moscow and the development of regional ethnography in Siberia, while S. A. Tokarev was actively involved in the scientific discourse between the «center» and the «periphery» on both sides of the complex integration process.

Substance use disorders and pharmacotherapies: exploring public knowledge and supportive attitudes

ABSTRACT Background: Despite available and effective prevention and treatment strategies for substance use disorders (SUD), drug overdose deaths in the US remain high. Further, limited public knowledge of SUD pharmacotherapies may contribute to increased stigmatization toward SUD medications and a lack of willingness to help people with SUD. Objectives: This study evaluated knowledge and attitudes about SUD pharmacotherapies and willingness to help people with SUD among a sample of U.S. adults. Method: Participants recruited through Amazon’s Mechanical Turk (N = 314; 62.1% male) completed online surveys evaluating knowledge, attitudes, and willingness to help by various demographic factors, history of substance use, and experience with someone with SUD. Results: Results revealed a significant difference in attitudes by race/ethnicity (F(1,307) = 11.85, p < .001). Participants with a personal history of substance use exhibited greater knowledge (F(1,312) = 31.94, p < .001) and willingness to help someone with a SUD (F(1,312) = 7.84, p = .005). Participants with experience with someone with a SUD also exhibited greater knowledge (F(1,311) = 19.42, p < .001) and willingness to help (F(1,311) = 13.63, p < .001). Conclusion: Results emphasize the importance of targeted education to bridge gaps in knowledge, enhance public attitudes, and promote willingness to help individuals with SUD. Utilizing public health strategies that promote empathy, willingness to help, and increase accessibility and acceptance of SUD treatment options, could be potential avenues that ultimately improve outcomes for individuals with SUD.

Clinical Benefit of Pegylated Liposomal Doxorubicin and High Prevalence of Pre-Existing Psychiatric Conditions in Patients with Desmoid-Type Fibromatosis.

Background/Objectives: Desmoid-type fibromatosis (DTF) is a locally invasive tumor composed of myofibroblast-like cells and collagen; it does not metastasize but can cause significant local morbidity. Most sporadic cases are associated with mutations in the CTNNB1 gene, which encodes beta-catenin. Various treatments have been used with differing efficacy and toxicity profiles. At our institution, pegylated liposomal doxorubicin (PLD) has become the preferred treatment for patients with DTF. We aim to describe our experience using PLD in patients with DTF who require treatment. Methods: A retrospective review of 61 DTF patients (41 females, 20 males) treated between 2000 and 2023 was conducted to assess the efficacy and toxicity of PLD. Results: Of the 26 patients treated with PLD, 23 had follow-up clinical data to assess benefit. Twenty-one showed clinical benefit, and only one progressed. Two patients did not benefit from PLD due to infusion reactions and chose alternative therapies. The primary side effect of PLD was hand-foot syndrome (HFS), but dose reduction and extended intervals allowed most patients to tolerate treatment. Other treatments, such as methotrexate, vinblastine/vinorelbine, and sorafenib, also showed activity but had significant toxicities, including severe HFS, malaise, and hypertension. Interestingly, 31 out of 61 patients had a pre-existing history of psychiatric conditions (primarily depression and anxiety), and 6 of 41 women had personal or family history of polycystic ovary syndrome (PCOS). Additionally, 15 patients had obesity, and 4 had hypothyroidism. Conclusions: PLD is an effective and well-tolerated treatment for DTF, with good clinical responses at lower, tolerable doses. The association of pre-existing psychiatric diagnoses, PCOS, and obesity warrants further investigation.

Immune checkpoint inhibitor-related diabetes mellitus associated with high signal intensity in diffusion-weighted magnetic resonance imaging of the pancreas at an early clinical stage.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but can give rise to immune-related adverse events such as ICI-related diabetes mellitus (DM). We herein present the case of a 59-year-old Japanese man with malignant melanoma who developed ICI-related DM after 18 months of nivolumab treatment. He experienced marked hyperglycemia and diabetic ketoacidosis without a personal or family history of diabetes. Laboratory findings revealed initial preservation of insulin secretion but a rapid decline in C-peptide levels in the absence of islet autoantibodies. He was therefore diagnosed with ICI-related DM. This case fulfilled the criteria for fulminant type 1 DM but lacked the typical human leukocyte antigen alleles associated with conventional type 1 diabetes. No metastasis or morphological changes were apparent on CT scans of the pancreas, and magnetic resonance cholangiopancreatography did not show dilation or interruption of the main pancreatic duct. However, diffusion-weighted magnetic resonance imaging revealed high signal intensity with low apparent diffusion coefficient values in the pancreas, likely indicative of fibrosis or infiltration of inflammatory cells. This case underscores that ICI-related DM should be considered a potential immune-related adverse event as well as pointing to the benefit of diffusion-weighted imaging for assessment of pancreatic involvement at an early stage of the disease.