Clinical Center Research Articles

Association of Anti-Müllerian Hormone on Oocyte Maturation, Fertilization, and Pregnancy Rates in Patients under Assisted Reproductive Technology Cycles: A Cross-Sectional Study.

Ovarian reserve is one of the most important factors that influences the success of assisted reproductive technology (ART). Recently, the role of anti-müllerian hormone (AMH) in ART has been investigated as a marker for the prediction of ovarian response. We aim to examine this relationship within a large Iranian population. In this cross-sectional study, we obtained data from 1000 infertile couples who referred to the Research and Clinical Centre of Yazd Infertility Clinic for in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Serum AMH levels, oocyte count, numbers of fertilised oocytes, endometrial thickness, and percentage of mature oocytes were measured. The relationship between AMH serum levels and the number and quality of oocytes and embryos in ART cycles was analysed. In the linear regression model, the log of the variables total dose of gonadotropin, two pronuclei (2PN), log oestradiol, total embryos, duration of stimulation, number of embryos transferred, protocol, and cause of infertility were significant predictors of log AMH. There appears to be a relationship between serum AMH levels in the early follicular phase and ovarian reserve. Higher serum AMH levels were also associated with shorter ART cycles.

Risk of Recurrence in Acute Anterior Uveitis

PurposeTo examine the frequency of recurrence and identify risk factors for recurrence in patients with acute anterior uveitis (AAU). DesignRetrospective cohort study from a single tertiary ophthalmic clinical centre. ParticipantsAll subjects with AAU identified from a database of Inflammatory Eye Disease presenting to Te Whatu Ora (Auckland, New Zealand) between 2008 and 2021. MethodsData was collected retrospectively from chart review and electronic patient records for all patients during the study period. Rates of recurrence were reported using Kaplan Meier estimator. Multivariate analysis of risk factors for recurrence were calculated using a marginal Cox regression model. Main Outcome MeasuresThe primary outcome measure was disease recurrence. Secondary outcome measure was moderate vision loss (≤20/50). Results2763 eyes of 2092 subjects with AAU were studied, with a median follow up time of 8.9 years, and a total follow up of 19,794.9 eye-years. Recurrence occurred in the ipsilateral eye in 1258 eyes (45.5%) and in the contralateral eye in 522 eyes (27.3%). Rates of ipsilateral recurrence over ten years were 38.1% for idiopathic disease, 43.2% for HLAB27/inflammatory arthritis, and 44.9% for viral uveitis. On multivariate analysis the following were associated with increased risk of ipsilateral recurrence: older age (p<0.001); Māori ethnicity (p=0.006); Asian ethnicity (p<0.001); HLA-B27/inflammatory arthritis (p<0.001); viral uveitis (p=0.018). There was no association with gender, smoking, bilateral disease, or hypertensive uveitis. Rates of contralateral eye involvement were significantly lower than ipsilateral eye recurrence. Contralateral recurrence at ten years was 15.2% in idiopathic uveitis, 37.6% in HLAB27/inflammatory arthritis, and 2.0% in viral uveitis. Risk factors identified for contralateral eye involvement were Māori ethnicity (p=0.003), Pasifika (Pacific Islanders) ethnicity (p=0.021), HLAB27/inflammatory arthritis (p<0.001). Moderate vision loss (≤20/50) was present in 411 eyes (14.9%) at final follow up and was more common if time to first recurrence was shorter (p<0.001). ConclusionsApproximately half of patients with AAU will develop recurrence in the ipsilateral eye and a quarter will have recurrence in the contralateral eye. Patients with viral disease have the highest risk of ipsilateral recurrence and lowest risk of contralateral recurrence. Patients with risk factors for recurrence should be managed and counselled appropriately to minimise the risk of visual loss and complications of uveitis.

OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway

BackgroundIntestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression.MethodsIn this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM.ResultsOur results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3β and resulted in increased β-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells.ConclusionsOLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.

Frequency of C9orf72, GRN, and MAPT pathogenic variants in patients recruited at the Belgrade Memory Center.

Most of the heritability in frontotemporal dementia (FTD) is accounted for by autosomal dominant hexanucleotide expansion in the chromosome 9 open reading frame 72 (C9orf72), pathogenic/likely pathogenic variants in progranulin (GRN), and microtubule-associated protein tau (MAPT) genes. Until now, there has been no systematic analysis of these genes in the Serbian population. Herein, we assessed the frequency of the C9orf72 expansion, pathogenic/likely pathogenic variants in GRN and MAPT in a well-characterized group of 472 subjects (FTD, Alzheimer's disease - AD, mild cognitive impairment - MCI, and unspecified dementia - UnD), recruited in the Memory Center, Neurology Clinic, University Clinical Center of Serbia. The C9orf72 repeat expansion was detected in 6.98% of FTD cases (13.46% familial; 2.6% sporadic). In the UnD subgroup, C9orf72 repeat expansions were detected in 4.08% (8% familial) individuals. Pathogenic variants in the GRN were found in 2.85% of familial FTD cases. Interestingly, no MAPT pathogenic/likely pathogenic variants were detected, suggesting possible geographical specificity. Our findings highlight the importance of wider implementation of genetic testing in neurological and psychiatric practice managing patients with cognitive-behavioral and motor symptoms.

Comparison of whole-blood sirolimus concentrations measured by EMIT-based Siemens Viva-ProE® System and LC-MS/MS in Chinese transplant patients

Sirolimus (SRL) is commonly used in transplant patients to prevent organ transplant rejection. The current guidelines recommend to perform SRL therapeutic drug monitoring regularly to improve treatment outcomes and avoid adverse effects. Consequently, a precise and accurate method for determining SRL is crucial in clinical practice. Currently, liquid chromatography–tandem mass spectrometry (LC-MS/MS) and immunoassays have been widely adopted for determining SRL concentrations. However, previous studies have shown that immunoassays exhibit a positive bias compared to LC-MS/MS. As the new updated version of the EMIT-based Viva-E® System (SVPS), this study aims to compare SRL blood concentrations measured by the SVPS and LC-MS/MS. The residual whole-blood samples obtained from transplant patients were simultaneously analyzed using the SVPS and LC-MS/MS, respectively. The correlation between the two assays was analyzed using the linear regression analysis and Deming linear regression. The Pearson correlation coefficient and Intraclass correlation coefficient (ICC) analysis were executed. The Paired Wilcoxon test and Bland-Altman analysis were performed to assess the concordance between the two methods. The SVPS considerably increased SRL concentration value by 46.62 % as compared to the LC-MS/MS method. When SRL concentrations measured by the SVPS were above 4.0 ng/mL, there was no significant difference between the corrected SVPS concentrations after using the Deming linear regression equation, indicating their interchangeability. Given the significant disparities observed between EMIT and LC-MS/MS, it is crucial to indicate the methodology and instruments in both TDM reports and future clinical guidelines. Our study also provides the conversion formulas between the SVPS and LC-MS/MS, which can be applied as a reference for different clinical centers.

Assessment of plasma cell-free DNA fragmentation for multi-cancer early detection: An independent clinical validation study.

e15037 Background: Cell-free DNA (cfDNA) in the circulation has gained significant attention due to its potential applications for non-invasive early cancer detection. Fragmentomics of cfDNA is emerging as a promising field of biomarker research, exhibiting the capability to sensitively detect multiple cancer types. In previous retrospective research, we developed an approach called PatternWGS for comprehensive analysis of cfDNA fragmentation patterns and presented a multi-cancer detection model. In this study, we aim to evaluate the performance of PatternWGS in an independent validation cohort including lung, breast, colorectal, liver, and gastric cancers from a new clinical center. Methods: Participants with confirmed diagnosis of lung, breast, colorectal or liver cancer were enrolled in the cancer group. Non-cancer participants without known presence of malignancies were recruited from the same clinical center. Plasma samples from patients with lung (n=47), breast (n=19), colorectal (n=14), liver (n=8) and gastric (n=6) cancers, along with 101 non-cancer individuals were collected in this study. cfDNA was isolated from plasma and stored within a month prior to the whole genome sequencing. The characteristics of cfDNA fragmentation integrating fragment size profiles, motif patterns, genomic coverage distributions were utilized to evaluate the performance for cancer signal detection. In addition, the performance of estimated cfDNA tumor fraction, using copy number aberrations (ichorCNA), was compared with our approach. Results: 94 patients with one of five types of cancers and 101 non-cancer controls were prospectively enrolled between July 2023 and November 2023. Among the cancer group, 64% were at early stages (Stage I: 48%, Stage II: 16%). A significantly higher proportion of shorter fragments was observed in cancer group, and the degree increased with increasing cancer stage. Overall sensitivity across cancer types and stages was 72.3%, and the specificity for non-cancer controls was 80%. As expected, the sensitivity of cancer detection is higher in late-stage patients compared to those in the early-stages (61% in stage I, 80% in stage II, 84.6% in stage III, and 91.7% in stage IV). The sensitivity of detecting lung (72% had stage I cancer), breast, colorectal, liver, and gastric cancers reached 57.4%, 84.2%, 85.7%, 87.5% and 100% respectively. The detection performance using cfDNA tumor fraction by ichorCNA demonstrated a relatively low overall sensitivity of 28.7% (24.6% for stage I-II, 44% for stage III-IV). Conclusions: This independent clinical validation study, which focused on exploring plasma cfDNA fragmentation, demonstrated ideal performance in early-stage cancer detection. The cfDNA fragmentation-based approach exhibited a superior sensitivity in detecting early cancer signals compared with copy number aberrations-based approach.

Chinese Guidelines for Medical Nutrition Therapy for Patients with Diabetes (2022 Edition).

Medical nutrition therapy (MNT) is the foundation of the comprehensive treatment of patients with diabetes. In 2010, the Chinese Clinical Nutritionist Center of the Chinese Medical Doctor Association developed the first Chinese guideline on MNT for patients with diabetes, and it was updated in 2015. Since then, new evidence has emerged in the field of MNT and metabolic therapy in patients with diabetes. The Nutrition and Metabolic Management Branch of the China International Exchange and Promotive Association for Medical and Health Care organized a team of experts from related institutions, including the Clinical Nutrition Branch of the Chinese Nutrition Society, Chinese Diabetes Society, Chinese Society for Parenteral and Enteral Nutri-tion, and Chinese Clinical Nutritionist Center of the Chinese Medical Doctor Association. Their task was to develop the Chinese Guidelines of Medical Nutrition Therapy in Diabetes (2022 Edition) in accordance with the requirements of the Guidelines for the Formulation/Revision of Clinical Guidelines in China (2022 Edition) by combining the questions raised and evidence gathered in clinical practices in China, to guide and standardize the clinical MNT.

Blood urea nitrogen to albumin ratio is a novel predictor of fatal outcome for patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high death rate and lacks a targeted therapy plan. The ratio of blood urea nitrogen to albumin, known as BAR, is a valuable method for assessing the outlook of various infectious diseases. The objective of this research was to evaluate the effectiveness of BAR in forecasting the outcome of individuals with SFTS. Four hundred and thirty-seven patients with SFTS from two clinical centers were included in this study according to inclusion and exclusion criteria. Clinical characteristics and test parameters of SFTS patients were analyzed between survival and fatal groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression suggested that BAR might serve as a standalone prognostic indicator for patients with SFTS in the initial phase (hazard ratio = 18.669, 95% confidence interval [CI]: 8.558-40.725, p < 0.001). And BAR had a better predictive effectiveness in clinical outcomes in patients with SFTS with an AUC of 0.832 (95% CI: 0.788-0.876, p < 0.001), a cutoff value of 0.19, a sensitivity of 0.812, and a specificity of 0.726 compared to C-reactive protein, procalcitonin, and platelet to lymphocyte ratio via receiver operating characteristic curve. KM (Kaplan Meier) curves demonstrated that high level of BAR was associated with poor survival condition in patients with SFTS. Furthermore, the high level of BAR was associated with long hospital stays and test paraments of kidney, liver, and coagulation function in survival patients. So, BAR could be used as a promising early warning biomarker of adverse outcomes in patients with SFTS.

Small World derived index to distinguish Alzheimer’s type dementia and healthy subjects

Abstract Background This article introduces a novel index aimed at uncovering specific brain connectivity patterns associated with Alzheimer's disease (AD), defined according to neuropsychological patterns. Methods Electroencephalographic (EEG) recordings of 370 people, including 170 healthy subjects and 200 mild-AD patients, were acquired in different clinical centres using different acquisition equipment by harmonising acquisition settings. The study employed a new derived Small World (SW) index, SWcomb, that serves as a comprehensive metric designed to integrate the seven SW parameters, computed across the typical EEG frequency bands. The objective is to create a unified index that effectively distinguishes individuals with a neuropsychological pattern compatible with AD from healthy ones. Results Results showed that the healthy group exhibited the lowest SWcomb values, while the AD group displayed the highest SWcomb ones. Conclusions These findings suggest that SWcomb index represents an easy-to-perform, low-cost, widely available and non-invasive biomarker for distinguishing between healthy individuals and AD patients.

SMART: A phase II study of sacituzumab govitecan (SG) with or without atezolizumab immunotherapy in rare genitourinary (GU) tumors such as small cell, adenocarcinoma, and squamous cell bladder/urinary tract cancer, renal medullary carcinoma (RMC) and penile cancer.

TPS4627 Background: Rare tumors of the GU tract often exhibit aggressive clinical behavior, yet lack effective standard of care treatment options. SG is an antibody-drug conjugate (ADC) targeting trophoblastic cell surface antigen 2 (Trop2) with a payload of SN-38, a topoisomerase inhibitor. SG monotherapy gained accelerated approval in pts with metastatic urothelial carcinoma (mUC) post platinum and immune-checkpoint inhibitor (ICI) therapy based on the TROPHY-U-01 trial (Tagawa S et al., JCO 2021). Atezolizumab is an anti-PD-L1 ICI approved for use in multiple solid tumors. SMART will evaluate the efficacy and safety of SG monotherapy or SG plus atezolizumab in select rare GU tumors. Methods: SMART is an open-label, non-randomized, Phase 2 trial. Pts must have locally advanced (unresectable) or metastatic GU tumors of the following histologies: small cell carcinoma, squamous cell carcinoma, or primary adenocarcinoma of the bladder or urinary tract, RMC, or squamous cell carcinoma of the penis. Pts may be treatment-naïve or have received any number of prior therapies; pts with small cell carcinoma must have received a platinum-based regimen. Pts treated with a PD-1/PD-L1 ICI will be assigned to Cohort A/Treatment Arm 1 and will receive SG monotherapy (10mg/kg IV, D1 and D8 of 21 day cycles). Pts without prior ICI treatment will be assigned to Cohort B/Treatment Arm 2 and will receive SG (10mg/kg IV, D1 and D8 of 21 day cycles) with concomitant atezolizumab (1200mg IV, D1 of 21 day cycles). Treatment will continue until disease progression (max duration of treatment 5 years) or intolerable side effects. The primary endpoint is objective response rate (ORR) (RECIST v1.1) for each Cohort, with restaging every 3 cycles. Secondary endpoints include safety, clinical benefit rate (CR+PR+SD), median PFS/OS for each Cohort, and ORR for each histology. Exploratory analyses include determination of baseline tumor mutation and transcriptional profile, Trop2 expression, ctDNA/CTCs, peripheral blood immune subsets and cytokine profile correlation with response, and correlation of UGT1A1 allele genotype with response and safety. This study utilizes a Simon minimax two-stage design, with enrollment of up to 43 evaluable pts (accrual ceiling of 60 pts). Cohort A will enroll 11 pts in Stage 1; if 1 or more of the first 11 pts has a response (unacceptably low rate of 5%, p0=0.05; alpha 0.10, beta=0.20), accrual will continue into Stage 2 up to 18 evaluable pts. Cohort B will enroll 16 evaluable pts in Stage 1; if 2 or more pts have a response (unacceptably low rate of 10%, p0=0.10; alpha 0.10, beta=0.10), accrual will continue in Stage 2 up to a total of 25 evaluable pts. This study is open at the NIH Clinical Center (CC); enrollment may open at 1-2 additional centers. Clinical trial information: NCT06161532 .

Improving access to infusion services: Results of an operational sprint.

e13522 Background: As a large clinical academic cancer center growing from 40,772 unique patients in 2021 to 44,416 patients in 2022, access for patients to begin therapy in the infusion suite was delayed by 3.2 days. In addition to delays in care the center experienced decreased patient satisfaction related to timeliness of scheduling and an inflexible scheduling template that did not allow for the maximization of chair assets. An infusion sprint was launched to address the challenges with the main goal of providing a seamless patient experience while ensuring that all 60 chair assets were maximally utilized. The multi-disciplinary team sought to accomplish this through a disciplined evaluation and intervention program with the goals of increasing access, improving patient satisfaction and growing operating income. Methods: In February 2022, a multi-disciplinary team was assembled to develop and implement a plan to increase access to the infusion suite over a period of 6 months. The team utilized LEAN-Six Sigma principles to characterize current state, desired future state and tactical interventions with metrics. Access data, available infusion appointments and activities occurring in chairs were analyzed with the goal of maximizing utilization. This was accomplished through the development of an active asset management methodology that compared available infusion appointment hours in the schedule to the actual completed hours which allowed the center to determine the growth opportunity within the current chair count. Financial performance was reviewed, and a pilot of an AI-based scheduling platform was launched. Results: Data collected in December 2022 showed that the pilot increased average daily chemotherapy infusion patient volume by 10% and overall volume by 11% over prior fiscal year from October 2021 to September 2022. Daily scheduling escalations manually resolved by leadership decreased 54% between May 2022 and September 2022. Newly created chair utilization methodology showed increased utilization from 62% to 82% in 7 months and patient satisfaction increased from 76.97% to 81.18% for “Timeliness of Scheduling.” These initiatives also resulted in an 18% increase in infusion/pharmacy income from operations from October 2021 to September 2022. All of this was accomplished without adding staff to the workforce or chairs to the infusion suite. Conclusions: A focused, intentional, multi-disciplinary infusion sprint conducted over 6 months resulted in increases of patient access, increased patient satisfaction and revenue. External validity is limited by its one site design with future investigation planned at other sites within the cancer care network to determine if results can be reproduced.

The impact of simulated operating rooms in a clinical skill center on operating room students’ skills and satisfaction: A semi experimental study

The impact of simulated operating rooms in a clinical skill center on operating room students’ skills and satisfaction: A semi experimental study

Investments in Scientific Teaching Staff – Main Determinant of Quality Medical Education

Abstract Science has emerged as a powerful tool to facilitate researchers in conducting trustful summary of achievements in clinical practice. Science has a leading role in modern medicine as it allows prediction of the future development of new scientific ideas, formulating the prospects for future development. The purpose of the article was to make a comparative analysis and evaluation of the allocated funds for scientific and teaching staff hired under second employment contract in the university clinics or accredited teaching hospitals or departments for clinical training of the Medical University – Sofia for the period 2013-2022, and to show the effectiveness of investing in human capital. For the purposes of the research, the following were used: documentary method, analysis and synthesis and comparative method. During the analyzed period, a permanent tendency towards a decrease in the total number of clinical teachers in all clinical training centres was observed. The total amount of funds spent on the wage fund for the ten-year period increased by 35.7% compared to the beginning of the period. The increase in the funds for the salary fund of the clinical teachers stems from the policy that was introduced in 2016 with the Collective Labor Agreement – together with the social partners stimulation (bonus) for theoretical and practical training of medical students both in the Bulgarian language (state order), as well as payment for English language training. With a view to improving the quality of education of future healthcare Professionals, MU – Sofia continuously invests its own funds in its scientific and teaching staff. Proof of the effectiveness of the invested funds are the results of the last 10 years of the Rating System of the higher schools in the Republic of Bulgaria, in which MU – Sofia was ranked first in the five professional areas in which it conducts training.

Множественная лекарственная устойчивость уропатогенов как фактор риска при оказании медицинской помощи (опыт Центральной Болгарии)

The emergence of resistance to multiple antimicrobial agents in uropathogenic bacteria has become a significant public health problem. These microorganisms are the cause of urinary tract infections, which are among the most frequently treated diseases in the outpatient medical care. A cross-sectional study was conducted among 353 outpatients over 18 years of age with positive urine sample culture. It involved measuring the index of multiple antibiotic resistance of uropathogens causing infections among individuals. The research was conducted in the period January – June 2023 at a private clinical laboratory center located in Stara Zagora, Bulgaria. One third of the isolates of E. coli and more than a half of those of Klebsiella pneumoniae had a measured MAR index greater than 0.2, with confirmatory high rates of resistance to aminopenicillins and cephalosporins. Alarmingly high MARI values were measured in all representatives of Enterococcus faecalis, Enterobacter species and Pseudomonas aeruginosa. These strains were also established to have high levels of resistance (varying from 58.3 to 100 %) to some of antimicrobial medicines most commonly prescribed in the outpatient healthcare. Findings of this study emphasize the importance and seriousness of the existing problem with the increasing prevalence of uropathogenic microorganisms with multiple resistance to oral antibiotics. This creates elevated risks of failure to provide effective treatment for patients.

Atezolizumab plus bevacizumab (A+B) as first-line systemic therapy for advanced hepatocellular carcinoma (HCC): A multi-institution analysis of patient outcomes based on Child Pugh (CP) and ALBI liver function.

4099 Background: A+B is standard of care for advanced HCC in the first line setting, although was only evaluated in patients with CP class A liver function in IMbrave150. We sought to determine outcomes of patients in the real-world setting. Methods: We conducted a multi-institution retrospective analysis of patients with HCC who received A+B as first-line systemic therapy between March 2018 and November 2023, at Mayo Clinic and University Hospitals Seidman Cancer Center. Treatment response was evaluated, and progression free survival (PFS) and overall survival (OS) were determined using the Kaplan Meier method. Multivariate analyses were performed using Cox proportional hazard regression method. Results: Among patients with HCC (n=322), 226, 86, and 10 had CP-A, -B, and -C liver function, while 120, 177, and 25 had ALBI grade 1, 2, and 3 liver function. Median age was 66.5 years, 78.6% were male, and 82.6% were white. Liver disease causes included hepatitis B (5.3%) and C (34.8%), ethanol use (26.1%), and non-alcoholic steatohepatitis (15.5%). Macrovascular invasion was seen in 42.9%, and 30.4% had extrahepatic metastatic disease. Median OS for patients with CP-A5/6 was 21.6 months, B7 (n=49) was 9.1 months, and B8-C12 was 4.7 months ( p&lt;0.0001). Median OS by ALBI grade was 34.9, 11.7, and 4.7 months for grades 1, 2, and 3. Median PFS was 8.9, 6.4, and 2.7 months for CP-A5/6, B7, and B8-C12 ( p&lt;0.0001). Median PFS by ALBI grade was 11.0, 6.4, and 3.7 months for grades 1, 2, and 3 ( p=0.0001). Among patients with CP-A, those with ALBI grade 1 had mOS of 34.9 months versus 14.2 months for those with grade 2. Partial response was seen in 29.2%, 19.8% and 10.0% of patients with CP-A, -B, and -C, while 32.7%, 33.7%, and 40.0% had stable disease. In a univariate analysis, factors predictive of shorter OS included CP-B7 or CP-B8-C12, ALBI grade 2 or 3, hepatitis B, poorer ECOG performance status (PS), macrovascular invasion, non-white race, and lack of prior surgery or embolization. In multivariate analyses, CP score, ALBI grade, hepatitis B, ECOG PS, and macrovascular invasion were significantly associated with survival. There was significant interaction between CP and ALBI grade (Table). Conclusions: A+B remains a viable option in patients with CP-B7 liver function, although benefit is significantly less than those with CP-A. ALBI score has predictive value and can identify two prognostic groups among those with CP-A liver function. [Table: see text]

Multidrug resistance of uropathogens as a risk factor in providing medical care to patients from central Bulgaria

The emergence of resistance to multiple antimicrobial agents in uropathogenic bacteria has become a significant public health problem. These microorganisms are the cause of urinary tract infections, which are among the most frequently treated diseases in the outpatient medical care. A cross-sectional study was conducted among 353 outpatients over 18 years of age with positive urine sample culture. It involved measuring the index of multiple antibiotic resistance of uropathogens causing infections among individuals. The research was conducted in the period January – June 2023 at a private clinical laboratory center located in Stara Zagora, Bulgaria. One third of the isolates of E. coli and more than a half of those of Klebsiella pneumoniae had a measured MAR index greater than 0.2, with confirmatory high rates of resistance to aminopenicillins and cephalosporins. Alarmingly high MARI values were measured in all representatives of Enterococcus faecalis, Enterobacter species and Pseudomonas aeruginosa. These strains were also established to have high levels of resistance (varying from 58.3 to 100 %) to some of antimicrobial medicines most commonly prescribed in the outpatient healthcare. Findings of this study emphasize the importance and seriousness of the existing problem with the increasing prevalence of uropathogenic microorganisms with multiple resistance to oral antibiotics. This creates elevated risks of failure to provide effective treatment for patients.

Evaluation of a summer program for minority high school students in the clinical cancer center: The Future Gen Cancer Scholars program.

e13703 Background: Individuals from minoritized communities receive less cancer screening, have higher stage at cancer diagnosis, and experience higher death rates. Helping minority high school students find a pathway to enter college and continue with advanced education and training and become leaders in cancer treatment, research and prevention may help reduce these inequities. Many public high schools in urban centers struggle in STEM education. The Rhode Island Hospital / Legorreta Cancer Center at Brown University partnered with the Papitto Opportunity Connection in Rhode Island to create the Future Gen Cancer Scholars program. Methods: High school students were invited to apply from Providence and surrounding communities. Accepted applicants became paid hospital employees and received training in professional conduct, protected health information and other skills necessary to shadow physicians in inpatient and outpatient settings. The summer curriculum included physician shadowing, radiology, pathology, student run tumor boards, seminars and community outreach. Pre/post-surveys were collected where students rated their experiences and beliefs regarding cancer careers on a 5-point Likert scale. Open-ended questions were added to evaluate interest in pursuing a career in oncology. Results: 20 high school students participated in the program’s first cohort. 70% self-identified as Hispanic/Latinx and 30% as African American, 85% were female, 90% attended a public school. Pre- and post-surveys were completed by 17 students. The 5-point Likert scale showed improvement in an understanding of oncology careers (pre, 3.9; post, 4.5), interest in pursuing a related career (pre, 3.1; post, 3.8), and recognition of available educational resources within their communities (pre, 3.9; post 4.3). Confidence in overcoming educational access barriers slightly decreased (pre-4.1; post-3.8) due to the increased awareness of the length, cost and process of medical training. Most students described the Future Gen Program as helping them identify career goals and a path forward. Conclusions: The Future Gen program helped solidify minority high school students’ desire to become leaders in cancer care and may provide a path forward to achieve this goal. We will track students’ educational and research achievements over time to measure the program’s impact. The establishment of a successful local model can provide a framework for a nationwide program.

Randomized, placebo-controlled trial of atorvastatin to prevent hearing loss in patients with head and neck squamous cell carcinoma receiving cisplatin based chemoradiation (CRT).

TPS12153 Background: Cisplatin chemotherapy is associated with several adverse effects, including a permanent, high-frequency, sensorineural hearing loss in about 50% of patients. Preclinical studies suggest that statin drugs can mitigate cisplatin ototoxicity (Fernandez et al., Hearing Research 2020). In our prior combined retrospective/prospective dataset of patients with head and neck squamous cell carcinoma (HNSCC) treated with cisplatin-based CRT, the incidence of CTCAE grade ≥ 2 hearing loss was 29.4% in statin non-users, versus 9.7% in atorvastatin users (Fernandez et al., J Clin Invest 2021). An adjusted odds ratio analysis indicated that atorvastatin users are significantly less likely to develop hearing loss versus statin non-users (odds ratio 0.47), providing the rationale for a randomized, controlled, prospective study. Methods: This multi-center, randomized, placebo-controlled study is enrolling patients with previously-untreated, locally advanced head and neck squamous cell carcinoma (HNSCC) for which cisplatin-based chemoradiation is indicated, either in the definitive or adjuvant setting. Patients who will be treated with cisplatin (at 75-100 mg/m2 bolus every three weeks or 40 mg/m2 weekly) are eligible. Patients currently taking a statin or those without measurable hearing in at least one ear are excluded. A baseline audiogram is performed, and patients are randomized to atorvastatin (40 mg/day) or placebo, which is started 2-7 days before CRT and taken daily until 3 months after completion of CRT. Post-treatment audiometry is repeated at 3 months and 2 years after CRT, along with collection of patient-reported outcomes on hearing, tinnitus, and peripheral neuropathy. Patients are monitored for liver and muscle toxicity, with dose de-escalation or cessation of atorvastatin as needed. The primary endpoint is the incidence of CTCAE grade ≥2 hearing loss at 3 months after CRT. Secondary endpoints include other treatment related grade 3-4 adverse events, overall survival, and disease-free survival. Up to 214 subjects will be enrolled at 4 U.S. sites (NIH Clinical Center, Emory University, University of Maryland, University of Rochester). Funding: NIH/NIDCD, U01 DC020452 and intramural project ZIA DC000079. Clinical trial information: NCT04915183 .

The six scoring systems' prognostic value in predicting 24-hour mortality in septic patients.

The use of scoring systems contributes to the faster identification of septic patients, especially those at a high risk of a fatal outcome. The best scoring system does not exist, so the search for the optimal one is always current. The aim of this study is to estimate the prognostic value of the six scoring systems in predicting 24-hour mortality among septic patients presented at the emergency department. An observational retrospective study was conducted in the Emergency Triage Room (ETR) of the Emergency Center (EC) at the University Clinical Center of Serbia (UCCS) in Belgrade. Consecutive septic patients, according to the Sepsis-3 definition, with or without shock, presented to the ETR and then hospitalized in Intensive Care Units were included in the study. Mortality data within 24 h and on the 28th day were extracted from the Hospital information system or the National mortality database. Scoring systems including sequential organ failure assessment (SOFA), quick sequential organ failure assessment (qSOFA), systemic inflammatory response syndrome (SIRS), National early warning score (NEWS), sepsis patient evaluation in the emergency department (SPEED), and mortality in emergency department sepsis (MEDS) were analyzed for all patients utilizing the available data. The primary outcome of this study was death within 24 hours of triage. Receiver operating characteristic (ROC) analysis was used to determine the most effective scoring system. Lactate was then added to this system to enhance its predictive accuracy. Nineteen out of 120 patients included in the study (15.8%) experienced death within 24 hours of triage. The twenty-eight-day mortality rate was 55%. SOFA score demonstrated the highest predictive value for 24-hour mortality but was only moderately predictive overall, with an area under the receiver operating curve (AUC) of 0.755 (95% CI 0.625-0.885). SPEED, MEDS, and NEVS exhibited modest discriminatory power [0.673 (95% CI 0.543-0.803), 0.665 (95% CI 0.536-0.794), 0.630 (95% CI 0.528-0.724)], while SIRS and qSOFA remained insignificant in predicting 24-hour mortality. The predictive value of the SOFA score was increased by the addition of lactate (AUC 0.865, 95% CI 0.736-0.995; p=0.0081). All scores demonstrated better and satisfactory predictive power for 28-day mortality. SOFA, with the addition of lactate, is a complex but reliable tool for the early stratification of septic patients who are presenting at an emergency department.

The utility of HPV16 E6 as a potential biomarker for HPV-related cancers in HIV-infected men who have sex with men.

10526 Background: The burden of HPV-related cancers, including oropharyngeal and anal cancers, poses a significant challenge. Although recent advancements in screening for anal cancer have been made for HIV-infected men who have sex with men (HIV-MSM), establishing effective screening protocols for oropharyngeal cancer remains ongoing. The early oncoprotein HPV16 E6 presents as a promising biomarker for the detection of HPV-associated cancers in this population as well. We investigated the utility of HPV16 E6 in HIV-MSM. Methods: We conducted a retrospective study using an HIV cohort at the AIDS Clinical Center of the National Center for Global Health and Medicine. Participants were all HIV-MSM and included those with HPV-related cancers or precancerous lesions such as oropharyngeal cancer, anal cancer, anal high-grade squamous intraepithelial lesions (aHSIL), and anal low-grade squamous intraepithelial lesions (aLSIL). All cancers and precancerous lesions were histologically confirmed. Frozen plasma samples taken at the time of diagnosis were evaluated. Additionally, when available, samples were retrospectively analyzed up to four years pre- and post-diagnosis. These specimens were sent to the German Cancer Research Center (DKFZ, Heidelberg, Germany) for analysis of antibodies against the early oncoproteins of carcinogenic mucosal HPV types, particularly HPV16 and other high-risk HPVs. Results: One hundred thirty-seven patients living with HIV (PWH) were included in the analysis. The distribution of PWH diagnosed with oropharyngeal cancer, anal cancer, aHSIL, and aLSIL was 6, 14, 96, and 9 respectively. Regarding HPV16 E6 seropositivity, 100% of patients with oropharyngeal cancer tested positive (6/6). Seropositivity rates for anal cancer, aHSIL, and aLSIL were 28.6% (4/14), 12.5% (12/96), and 11.1% (1/9) respectively (Table). Patients with oropharyngeal cancer exhibited the highest titer of HPV16 E6. Among the six patients with oropharyngeal cancer, one demonstrated persistent positivity from four years prior, and four showed positivity from one year prior. Two patients were not assessed as they were newly diagnosed at the time of the study. After chemoradiation treatment, their titers decreased but did not fall below the cutoff level during the follow-up period. In two cases of relapse, the titers, which had initially decreased with chemoradiation, increased again at least one year before the relapse diagnosis. Conclusions: The study demonstrated that screening for HPV16 E6 seropositivity is highly effective for the detection of oropharyngeal cancer in HIV-MSM. This could potentially contribute to early diagnosis and treatment of HPV-related cancers. [Table: see text]