Initial Diagnosis Research Articles

Clinical features and prognostic analysis of testicular relapse in pediatric acute lymphoblastic leukemia

Objective: To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL). Methods: Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. Results: The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis (HR=3.09, 95%CI 1.10-8.72), combined relapse (HR=4.26, 95%CI 1.34-13.52) and CAR-T cell therapy after relapse (HR=0.15,95%CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions: The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

Th17/1 and ex-Th17 cells are detected in patients with polyarticular juvenile arthritis and increase following treatment

BackgroundA better understanding of the pathogenesis of polyarticular juvenile idiopathic arthritis (polyJIA) is needed to aide in the development of data-driven approaches to guide selection between therapeutic options. One inflammatory pathway of interest is JAK-STAT signaling. STAT3 is a transcription factor critical to the differentiation of inflammatory T helper 17 cells (Th17s). Previous studies have demonstrated increased STAT3 activation in adult patients with rheumatoid arthritis, but less is known about STAT3 activation in polyJIA. We hypothesized that Th17 cells and STAT3 activation would be increased in treatment-naïve polyJIA patients compared to pediatric controls.MethodsBlood from 17 patients with polyJIA was collected at initial diagnosis and again if remission was achieved (post-treatment). Pediatric healthy controls were also collected. Peripheral blood mononuclear cells were isolated and CD4 + T cell subsets and STAT activation (phosphorylation) were evaluated using flow cytometry. Data were analyzed using Mann–Whitney U and Wilcoxon matched-pairs signed rank tests.ResultsTreatment-naïve polyJIA patients had increased Th17 cells (CD3 + CD4 + interleukin(IL)-17 +) compared to controls (0.15% v 0.44%, p < 0.05), but Tregs (CD3 + CD4 + CD25 + FOXP3 +) from patients did not differ from controls. Changes in STAT3 phosphorylation in CD4 + T cells following ex vivo stimulation were not significantly different in patients compared to controls. We identified dual IL-17 + and interferon (IFN)γ + expressing CD4 + T cells in patients, but not controls. Further, both Th17/1 s (CCR6 + CD161 + IFNγ + IL-17 +) and ex-Th17s (CCR6 + CD161 + IFNγ + IL-17neg) were increased in patients’ post-treatment (Th17/1: 0.3% v 0.07%, p < 0.05 and ex-Th17s: 2.3% v 1.4%, p < 0.05). The patients with the highest IL-17 expressing cells post-treatment remained therapy-bound.ConclusionsPatients with polyJIA have increased baseline Th17 cells, potentially reflecting higher tonic STAT3 activation in vivo. These quantifiable immune markers may identify patients that would benefit upfront from pathway-focused biologic therapies. Our data also suggest that inflammatory CD4 + T cell subsets not detected in controls but increased in post-treatment samples should be further evaluated as a tool to stratify patients in remission on medication. Future work will explore these proposed diagnostic and prognostic biomarkers.

68Ga-PSMA PET/CT in Initial Diagnosis and Bone Metastasis Evaluation in Saudi Patients with High-Grade Prostate Cancer

We present the first study performed in Saudi Arabia to evaluate 68Ga-PSMA PET/CT in prostate cancer (PCa) initial diagnosis and its added value in bone metastases (BM) diagnosis in such patients. Twenty-six male patients underwent prostate histopathological examination and all imaging studies (68Ga-PSMA PET/CT and CT); all of them were confirmed with high-grade PCa. Patients' mean PSA levels and Gleason score were 5.12±1.12 and 7.0±0.9, respectively. 68Ga-PSMA PET/CT (20/26; sensitivity of 76.9%) was superior to traditional CT (18/26; sensitivity of 69.2%) in PCa detection. There was a non-significant association (P=0.206) between patients' age and BM. Based on bone scintigraphy (BS), in patients without BM (n=16), 68Ga-PSMA PET/CT detected metastasis-suspicious lesions in six patients (37.5%) and negative results in ten patients (62.5%). 68Ga-PSMA PET/CT showed no false-negative cases among patients with confirmed BM using BS.In conclusion, 68Ga-PSMA PET/CT performed well in PCa initial diagnosis in Saudi male patients with high-grade tumors. 68Ga-PSMA PET/CT also accurately detected BM in all PCa patients with confirmed BM by BS. Larger prospective studies are urgently required to compare 68Ga-PSMA PET/CT diagnostic performance with other standard modalities in PCa and BM diagnosis.

Appendiceal Goblet Cell Carcinoma: Comparison of Classification and Staging Systems with Evaluation of the Prognostic Role of Immunohistochemistry Stains

Abstract Background Goblet cell carcinoma (GCC) of the appendix is a unique lesion that exhibits features of both adenocarcinoma and neuroendocrine tumors. Due to the rarity of this cancer, multiple grading (e.g., Tang, Yozu, and Lee) and staging systems (e.g., tumor, lymph nodes, and metastasis [TNM]) have been developed for classification. This study aimed to compare commonly used classification systems and evaluate the prognostic effectiveness immunohistochemical staining may or may not have for appendiceal GCC. Methods An electronic medical records review of patients who were diagnosed with GCC of the appendix in our hospital system from 2010 to 2020. The data were collected regarding the age at diagnosis, gender, initial diagnosis at presentation, operation(s) performed, final pathology results, current survival status, and year of recurrent disease or death year. Results Ten patients were evaluated. Seventy percent of the patients were above the age of 50 years at diagnosis. Postdischarge survival ranged from 1 month to 109 months postdiagnosis. Two patients expired from GCC at 13- and 54-months following diagnosis. When comparing the classification systems, Lee categorized more patients as high risk than Tang and Yozu. Immunohistochemical staining was analyzed using four staining methods: Ki67, E-cadherin, Beta-catenin, and p53. Tumor, lymph nodes, and metastasis staging has supportive evidence for worsening prognosis and overall survival secondary to the depth of invasion of the tumor. Conclusion Tumor, lymph nodes, and metastasis staging may be superior to the other classification systems in predicting overall mortality. Our study demonstrated that immunohistochemistry staining does not appear to have a significant impact in determining the prognosis for GCC of the appendix.

Small airway function in predicting asthma control in preschool children

AbstractAsthma control in children is often challenging. This retrospective cohort study aimed to investigate the potential contribution of small airway function in predicting asthma control within a 2‐ to 3‐month period following the initial diagnosis in preschool children with asthma. A total of 219 preschool children diagnosed with asthma were enrolled, and their follow‐up was conducted by pediatric pulmonary physicians. Clinical history and lung function results were collected for analysis. To identify risk factors associated with poor asthma control, a multivariable regression model was employed. Sixty‐nine of the patients (31.5%) exhibited poor asthma control. Poor adherence to therapy (14.5% vs. 6.0%, p = 0.038) and the presence of severe airway hyperresponsiveness (AHR) (20.6% vs. 1.6%, p &lt; 0.001) were more prevalent in the group with poor control. Additionally, baseline forced expiratory volume in 1 s in predicting (94.5% vs. 101.4%, p = 0.001), forced expiratory flows (FEF)50% (66.1% vs. 86.0%, p &lt; 0.001), FEF75% (60.9% vs. 75.3%, p = 0.001), and FEF25–75% (70.9% vs. 86.0%, p &lt; 0.001) were significantly lower in the poorly‐controlled group than those of well‐controlled group. There was no significant difference in forced vital capacity in predicting (FVC%) between the two groups (92.4% vs. 96.7%, p = 0.093). Multivariable regression model unveiled initial severe AHR (OR 8.595, 95%CI 1.241–59.537, p = 0.021) and decreased FEF50% (OR 0.971, 95%CI 0.949–0.994, p = 0.012) were significantly associated with short‐term poor asthma control. Preschool children with asthma who exhibites initial severe AHR and/or decreased FEF50% faces an elevated risk of encountering poor asthma control during the subsequent 2–3 months.

The impact of different clinicopathologic factors and salvage therapies on cervical cancer patients with isolated para-aortic lymph node recurrence

BackgroundCervical cancer patients with isolated para-aortic lymph nodes (PALN) recurrence were mainly associated with treatment failure. For these patients, radiotherapy, chemotherapy, surgery ± adjuvant therapy or chemoradiotherapy may be advised, however, no specific therapy has been proposed yet. This study aimed to explore factors influencing the prognosis of cervical cancer cases with isolated PALN recurrence and to find out an effective salvage therapy.MethodsCervical cancer cases with isolated PALN recurrence who received therapies in Zhejiang Cancer Hospital between January 2013 and June 2021 were analyzed retrospectively.ResultsCarcinoembryonic antigen (CEA) level > 10 ng/mL and positron emission tomography/computed tomography (PET/CT) imaging method used to detect the recurrence were found to be associated with the local control rate. PALN (positive), squamous-cell carcinoma-antigen (SCC-Ag) level (> 10 ng/mL) upon initial diagnosis, and CEA level (> 10 ng/mL), number of metastatic lymph nodes (several) at recurrence were associated with worse survival. Compared with surgery ± adjuvant therapy, chemotherapy (CT) alone or sequential chemoradiotherapy (SCRT) was associated with worse PFS or OS. Concurrent chemoradiotherapy (CCRT) after PALN recurrence could reduce the risk of the second recurrence. 3-year OS of cases after surgery ± adjuvant therapy was the highest (65%), followed by CCRT (45.7%), SCRT (38.9%), radiotherapy (RT) (33.3%), and CT (20.6%).ConclusionIn cervical cancer patients with isolated PALN recurrence, chemoradiotherapy or surgery ± adjuvant therapy may be preferred as the salvage treatment.

Households catastrophic health expenditure among older people with noncommunicable diseases: A cross-sectional study from Iran.

Noncommunicable diseases are one of the main difficulties faced by older adults in many countries. The study aimed to investigate the households'catastrophic health expenditure (CHE) among older people with noncommunicable diseases. This cross-sectional study was conducted between October and December 2022 in Semnan, Iran, with the participation of 400 older individuals suffering from diabetes and hypertension. The Content Validity Ratio(which is calculated based on necessity criterion) and Content Validity Index(which calculated based on relevance, transparency, and simplicity criteria) values of 0.94 and 0.89, respectively, confirmed the content validity of the researcher-made questionnaire. The occurrence of CHE was estimated using the World Health Organization's rule of "allocating at least 40% of non-food household costs to healthcare."Due to the qualitative nature of the data, the χ 2 test was utilized to assess the statistical association between demographic and background variables and occurrence of CHE. Older people with diabetes and hypertension had an annual direct medical costs of $821 averagely, which includes 9.7% for diagnosis, 23.9% for doctor visits, and 66.4% for treatment. Direct medical costs account for around 0.26 of nonfood costs, with 12.5% of seniors facing high medical charges. Age, marital status, type of basic health insurance, diabetes, the time elapsed since initial diabetes diagnosis, the severity of diabetes complications, and the development of diabetes-related visual impairments, are associated with CHE(p < 0.05). While the prevalence of CHE among elderly individuals with diabetes and hypertension is reasonably manageable, targeted promotional efforts are still necessary to protect those at high risk.

Dehydrated human amnion/chorion membrane to treat venous leg ulcers: a cost-effectiveness analysis.

To evaluate the cost-effectiveness of dehydrated human amnion/chorion membrane (DHACM) in Medicare enrolees who developed a venous leg ulcer (VLU). This economic evaluation used a four-state Markov model to simulate the disease progression of VLUs for patients receiving advanced treatment (AT) with DHACM or no advanced treatment (NAT) over a three-year time horizon from a US Medicare perspective. DHACM treatments were assessed when following parameters for use (FPFU), whereby applications were initiated 30-45 days after the initial VLU diagnosis claim, and reapplications occurred on a weekly to biweekly basis until completion of the treatment episode. The cohort was modelled on the claims of 530,220 Medicare enrolees who developed a VLU between 2015-2019. Direct medical costs, quality-adjusted life years (QALYs), and the net monetary benefit (NMB) at a willingness-to-pay threshold of $100,000/QALY were applied. Univariate and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty of model results. DHACM applied FPFU dominated NAT, yielding a lower per-patient cost of $170 and an increase of 0.010 QALYs over three years. The resulting NMB was $1178 per patient in favour of DHACM FPFU over the same time horizon. The rate of VLU recurrence had a notable impact on model uncertainty. In the PSA, DHACM FPFU was cost-effective in 63.01% of simulations at the $100,000/QALY threshold. In this analysis, DHACM FPFU was the dominant strategy compared to NAT, as it was cost-saving and generated a greater number of QALYs over three years from the US Medicare perspective. A companion VLU Medicare outcomes analysis revealed that patients who received AT with a cellular, acellular and matrix-like product (CAMP) compared to patients who received NAT had the best outcomes. Given the added clinical benefits to patients at lower cost, providers should recommend DHACM FPFU to patients with VLU who qualify. Decision-makers for public insurers (e.g., Medicare and Medicaid) and commercial payers should establish preferential formulary placement for reimbursement of DHACM to reduce budget impact and improve the long-term health of their patient populations dealing with these chronic wounds. Support for this analysis was provided by MiMedx Group, Inc., US. JLD, and RAF are employees of MiMedx Group, Inc. WHT, BH, PS, BGC and WVP were consultants to MiMedx Group, Inc. VD, AO, MRK, JAN, NW and GAM served on the MiMedx Group, Inc. Advisory Board. MRK and JAN served on a speaker's bureau. WVP declares personal fees and equity holdings from Stage Analytics, US.

Outcomes of rheumatic fever in Uganda: a prospective cohort study

Rheumatic heart disease is the largest contributor to cardiac-related mortality in children worldwide. Outcomes in endemic settings after its antecedent illness, acute rheumatic fever, are not well understood. We aimed to describe 3-5 year mortality, acute rheumatic fever recurrence, changes in carditis, and correlates of mortality after acute rheumatic fever. We conducted a prospective cohort study of Ugandan patients aged 4-23 years who were diagnosed with definite acute rheumatic fever using the modified 2015 Jones criteria from July 1, 2017, to March 31, 2020, enrolled at three rheumatic heart disease registry sites in Uganda (in Mbarara, Mulago, or Lira), and followed up for at least 1 year after diagnosis. Patients with congenital heart disease were excluded. Patients underwent annual review, most recently in August, 2022. We calculated rates of mortality and acute rheumatic fever recurrence, tabulated changes in carditis, performed Kaplan-Meier survival analyses, and used Cox regression models to identify correlates of mortality. Data were collected between Sept 1 and Sept 30, 2022. Of 182 patients diagnosed with definite acute rheumatic fever, 156 patients were included in the analysis. Of these 156 patients (77 [49%] male and 79 (51%) female; data on ethnicity not collected), 25 (16%) died, 21 (13%) had a cardiac-related death, and 17 (11%) had recurrent acute rheumatic fever over a median of 4·3 (IQR 3·0-4·8) years. 16 (24%) of the 25 deaths occurred within 1 year. Among 131 (84%) of 156 survivors, one had carditis progression by echo. Moderate-to-severe carditis (hazard ratio 12·7 [95% CI 3·9-40·9]) and prolonged PR interval (hazard ratio 4·4 [95% CI 1·7-11·2]) at acute rheumatic fever diagnosis were associated with increased cardiac-related mortality. These are the first contemporary data from sub-Saharan Africa on medium-term acute rheumatic fever outcomes. Mortality rates exceeded those reported elsewhere. Most decedents already had chronic carditis at initial acute rheumatic fever diagnosis, suggesting previous undiagnosed episodes that had already compounded into rheumatic heart disease. Our data highlight the large burden of undetected acute rheumatic fever in these settings and the need for improved awareness of and diagnostics for acute rheumatic fever to allow earlier detection. Strauss Award at Cincinnati Children's Hospital, American Heart Association, and Wellcome Trust.

Nuclear medicine and pediatric nephro-urology: a long-lasting successful partnership.

Congenital anomalies of the kidney and urinary tract, as well as urinary infections, are very frequent in children. After the clinical and laboratory evaluation, the first imaging procedure to be done is a renal and bladder ultrasound, but afterwards, a main contribution comes from nuclear medicine. Through minimally invasive and sedation-free procedures, nuclear medicine allows the evaluation of the functional anatomy of the urinary tract, and the quantification of renal function and drainage. If pediatric dosage cards provided by scientific societies are used, radiation exposure can also be low. In the pediatric conditions previously mentioned, nuclear medicine is used both for initial diagnosis and follow-up, mostly in cases of suspicion of ureteropelvic or ureterovesical junction syndromes, as well as vesicoureteral reflux or renal scars of febrile infectious episodes. Pediatric nephro-urology constitutes a significant workload of pediatric nuclear medicine departments. The following paragraphs are a revision of the renal radiopharmaceuticals, as well as the nuclear nephro-urology procedures - dynamic and static renal scintigraphy, and direct and indirect radionuclide cystography. A summary of the techniques, main indications, interpretation criteria and pitfalls will be provided. Some future directions for the field are also pointed out, among which the most relevant is the need for nuclear medicine professionals to use standardized protocols and integrate multidisciplinary teams with other pediatric and adult health professionals that manage these life-long pediatric pathologies, which are recognized as an important cause of adult chronic kidney disease.

Diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery

Objective: To analyze the diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery (AAOCA). Methods: This is a retrospective case series study. From January 2016 to July 2023, 24 cases of high-risk AAOCA underwent surgical treatment in Department of Cardiac Surgery, Guangdong Provincial People's Hospital. There were 18 males and 6 females, operatively aged (M (IQR)) 13 (26) years (range: 0.3 to 57.0 years). They were confirmed by cardiac ultrasound and cardiac CT, all of which had anomalous coronary running between the aorta and the pulmonary artery. There were 15 cases of the right coronary artery from the left aortic sinus of Valsalva, 6 cases of left coronary artery from the right aortic sinus of Valsalva, 3 cases of the sigle coronary artery. Only 3 patients had no obvious related symptoms (2 cases were complicated with a positive exercise stress test and 1 case with other intracardiac malformations), 21 cases had a history of chest tightness, chest pain, or syncope after exercise. Three patients suffered syncope after exercise and underwent cardiopulmonary resuscitation (2 cases were treated with an extracorporeal membrane oxygenerator (ECMO)). The gap from the first symptom to the diagnosis was 4.0 (11.5) months (range: 0.2 to 84.0 months). The detection rate of coronary artery abnormalities suggested by the first cardiac ultrasound was only 37.5% (9/24). Seven patients were complicated with other cardiac diseases (4 cases with congenital heart defects, 2 cases with coronary atherosclerotic heart disease, 1 case with mitral valve disease). Results: All 24 patients underwent surgical treatment (23 cases underwent abnormal coronary artery unroofing, 1 case underwent coronary artery bypass grafting), and 5 patients underwent other intracardiac malformation correction at the same time. There were no death or surgery related complications in the hospital for 30 days after the operation. A patient with preoperative extracorporeal cardiopulmonary resuscitation was continuously assisted by ECMO after emergency AAOCA correction and had complications such as limb ischemia necrosis and renal dysfunction after the operation. During the follow-up of 2.2 (3.3) years (range: 1 month to 7.2 years), one patient who previously underwent percutaneous transluminal coronary angioplasty with a stent implant experienced significant postoperative symptomatic relief, and the other discharged patients had no related symptoms. Conclusions: The accurate rate of initial diagnosis for high-risk AAOCA is still low, but the risk of cardiovascular accidents is high. For sports-related chest pain and other symptoms, more attention should be paid to the detection of AAOCA, especially for adolescents. Exercise stress testing can be helpful in evaluating the cardiovascular risk of asymptomatic AAOCA. Instant surgical treatment can achieve satisfactory curative effects.

Abstract B024: Immune exhaustion and reversal of progestin-related immune modulation in adaptive resistance to levonorgestrel intrauterine device for treatment of atypical hyperplasia and early endometrial cancer

Abstract Background: A growing proportion of women diagnosed with atypical hyperplasia (AH) and early-stage endometrioid endometrial cancer (EEC) require nonsurgical treatment options. Our previously published phase II clinical trial of the levonorgestrel intrauterine device (LIUD) for AH and grade 1 EEC (G1EEC) demonstrated 83% response rate at 1 year; however, prospective long-term follow-up data and determinants for duration of response to LIUD are limited. Methods: Follow-up data from patients that participated in our prospective phase II trial of LIUD as a nonsurgical approach for AH and G1EEC were collected from medical records. Duration of response and time to relapse were evaluated. Spatial transcriptomic profiling from longitudinal biopsy samples from pre-treatment (n=5), on-treatment (n=5), and disease relapse lesions (n=3) were evaluated using digital spatial profiling (DSP, Nanostring GeoMX Whole Transcriptome Atlas). In silico cell type deconvolution was performed and pathway analyses was conducted using gene set variation analysis enrichment. Results: Of 43 participants exhibiting initial response to LIUD, 41 had follow-up data. Sixteen experienced disease relapse (39%) with a median time to relapse of 17 months after initial response. Clinical factors associated with shorter duration of response included age (HR 0.95, p=0.021), initial diagnosis of G1EEC (HR 3.51, p=0.014), premenopausal status (HR 3.85, p=0.039), and Hispanic ethnicity (HR 3.45, p=0.017). Pre-treatment IGF1 and IGF2 expression levels were positive predictors of duration of response (HR 0.44 and 0.45, respectively, p&amp;lt;0.05). DSP results revealed that LIUD increased NK cells (log2FC=46.13, FDR=0.004), and lymphocyte cytotoxicity signaling markers GZMB (log2FC=1.06, padj=0.023) and PRF1 (log2FC=1.62, padj=0.004), but NK cells were reduced in relapse lesions (log2FC=-55.96, FDR=0.02) as was PRF1 expression (log2FC=-1.87, padj=0.038). Multiple immune-related pathways (IFNα and IFNγ response, TGFβ signaling) were significantly upregulated in relapse lesions compared to matched pre-treatment lesions (FDR&amp;lt;0.05). IDO1 expression, a marker for immune exhaustion, was upregulated in relapse lesions compared to matched pre-treatment and on-treatment lesions (log2FC=2.56, FDR=0.01). Conclusions: While LIUD for treatment of AH or G1EEC has excellent initial response rates, upfront resistance, and relapse after initial response to LIUD impacts nearly half of patients. Our study shows progestin-related immunomodulatory effects, including increased NK cell infiltration and lymphocyte cytotoxicity. Immune mechanisms for relapse are implicated here, including reversal of progestin-related immunomodulatory effects (decreased NK cell infiltration and lymphocyte cytotoxicity) and increased immune exhaustion (prolonged IFNα and IFNγ response and increased IDO1 expression in relapse lesions). Thus, relieving immune exhaustion may increase durability of response to LIUD for treatment of AH or G1EEC. Citation Format: Mikayla B. Bowen, Brenda Melendez, Qian Zhang, Richard Yang, Bryan Fellman, Barrett Lawson, Naomi Adjei, Joseph Celestino, Tri Nguyen, Khalida Wani, Bhavana Singh, Christof Straub, Liang Zhang, Cheryl Tan, Felicia New, Diana Urbauer, Alexander Lazar, Karen Lu, Jennifer Wargo, Shannon N. Westin, Melinda S. Yates. Immune exhaustion and reversal of progestin-related immune modulation in adaptive resistance to levonorgestrel intrauterine device for treatment of atypical hyperplasia and early endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B024.

Middle Facet Tarsal Coalition in a National Collegiate Athletic Association Basketball Athlete: An Exploration Clinical Case Report

The patient is a 22-year-old female basketball player initially diagnosed with a calcaneal fracture. Five months after the pain began, the patient was referred to a foot and ankle surgeon and diagnosed with middle facet tarsal coalition. The patient received one X-ray-guided subtalar steroid injection and two platelet-rich plasma injections to aid in pain relief while completing her senior year of collegiate basketball. She elected to end her senior season early to have the recommended subtalar fusion surgery. The surgery ended her basketball career but provided pain-free activities of daily living. This case presents unique components compared with available literature on how injury presentation in adult populations can complicate a timely and accurate initial diagnosis. This case is also unique because despite conservative efforts, a surgical fusion was required to optimize pain and function during activities of daily living.

Japan's healthcare delivery system: From its historical evolution to the challenges of a super-aged society.

Although Japan's healthcare delivery system is highly regarded internationally, the COVID-19 pandemic has exposed its structural problems. Behind these issues lies a history of medical care provisions supported mainly by an unrestricted, "free labeling" system, and independently financed private hospitals. In addition, patients have a high degree of freedom of choice under the Japanese medical insurance system, making it difficult to provide comprehensive and continuous health management from initial diagnosis and treatment (primary care), specialized treatment, to supporting a return to home, providing nursing care and lifestyle support. As Japan becomes a "super-aged" society with individuals over 65 making up over 30% of the population, the nature of medical care will have to undergo major changes. Medical care's basic function must still be the treatment and cure of patients, but the system will also have to provide support. That means conceiving of care in a way that treats a person's life with dignity and does not sacrifice life for treatment. The implementation of a family doctor function and the clarification of the functions and roles of small and medium-sized community-based hospitals that support this function, as well as the establishment of a community comprehensive care network with multidisciplinary cooperation that goes beyond medical care, should also be set forth in future regional medical care plans.

Conditional survival analysis and dynamic survival prediction for intracranial solitary-fibrous tumor/hemangiopericytoma

BackgroundAs the form of World Health Organization Central Nervous System (WHO CNS) tumor classifications is updated, there is a lack of research on outcomes for intracranial combined solitary-fibrous tumor and hemangiopericytoma (SFT/HPC). This study aimed to explore conditional survival (CS) pattern and develop a survival prediction tool for intracranial SFT/HPC patients.MethodsData of intracranial SFT/HPC patients was gathered from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. The patients were split into training and validation groups at a 7:3 ratio for our analysis. CS is defined as the likelihood of surviving for a specified period of time (y years), given that the patient has survived x years after initial diagnosis. Then, we used this definition of CS to analyze the intracranial SFT/HPC patients. The least absolute shrinkage and selection operator (LASSO) regression and best subset regression (BSR) were employed to identify predictive factors. The Multivariate Cox regression analysis was applied to establish a novel CS-based nomogram, and a risk stratification system was developed using this model.ResultsFrom the SEER database, 401 patients who were diagnosed with intracranial SFT/HPC between 2000 and 2019 were identified. Among them, 280 were included in the training group and 121 were included in the internal validation group for analysis. Our study revealed that in intracranial SFT/HPC, 5-year survival rates saw significant improvement ranging from 78% at initial diagnosis to rates of 83%, 87%, 90%, and 95% with each successive year after surviving for 1–4 years. The LASSO regression and BSR identified patient age, tumor behavior, surgery and radiotherapy as predictors of CS-based nomogram development. A risk stratification system was also successfully constructed to facilitate the identification of high-risk patients.ConclusionThe CS pattern of intracranial SFT/HPC patients was outlined, revealing a notable improvement in 5-year survival rates after an added period of survival. Our newly-established CS-based nomogram and risk stratification system can provide a real-time dynamic survival estimation and facilitate the identification of high-risk patients, allowing clinicians to better guide treatment decision for these patients.

Incidence and Factors Associated With Second Primary Invasive Melanoma in Norway

Patients diagnosed with a primary melanoma are at high risk of subsequent melanomas. Understanding the risk of second primary invasive melanoma and associated factors is crucial to optimize patient follow-up. To assess the incidence rate of second primary invasive melanoma and time between the first and second primary invasive melanoma in the Norwegian population. This population-based cohort study included data from deidentified records of all invasive melanomas diagnosed in Norway in 2008 to 2020, obtained from the Cancer Registry of Norway. Data were from adults aged 18 years or older diagnosed with a first primary melanoma. Data analysis was performed from March to August 2023. The main outcome was the incidence rate of second primary invasive melanoma at least 30 days after the first. Accelerated failure time models were fitted to examine potential associations with patient and tumor characteristics. Median time between first and second primary melanomas and 95% CIs were calculated. The likelihood of, and median interval for, second primary melanomas on the same or different site as the first primary were calculated. A total of 19 196 individuals aged 18 years or older were diagnosed with a first primary melanoma. The mean (SD) age at diagnosis of the first primary melanoma was 62 (16) years (range, 18-104 years), and 9763 (51%) were female. The incidence rate in the year following diagnosis was 16.8 (95% CI, 14.9-18.7) per 1000 person-years, which decreased to 7.3 (95% CI, 6.0-8.6) during the second year and stabilized thereafter. Median time between first and second primaries decreased with advancing age and was 37 months (95% CI, 8-49) in patients younger than 40 years, 18 (95% CI, 13-24) in patients aged 50 to 59 years, and 11 (95% CI, 7-18) in patients aged 80 years or older. The second primary was on the same site as their first primary for 47% (359 patients), and on a different site for 53% (407 patients). The median interval until second melanoma on the same site as the initial melanoma was 12 (95% CI, 7-19) months in men and 22 (95% CI, 11-35) months in women. Older age and male sex were associated with an increased risk, suggesting that increased surveillance intensity may be considered for men, especially those older than 50 years, for at least 3 years after their initial diagnosis, regardless of the characteristics of their first invasive melanoma.

Salvage high-dose rate brachytherapy for local recurrence of prostate cancer after radical prostatectomy

Background. The current need for optimization of salvage treatment methods is dictated by the growing expansion of indications for radical prostatectomy in many centers in the developed countries of the world.Aim. To evaluate the effectiveness, toxicity, and technical characteristics of high-dose rate brachytherapy in treatment of local prostate cancer (PCa) recurrences after radical prostatectomy.Materials and methods. Between January 2015 and December 2020, salvage high-dose rate brachytherapy was performed in 17 patients at the Russian Scientific Center of Roentgenology and Radiology for local recurrence of PCa after radical prostatectomy. All patients underwent multiparametric magnetic resonance imaging of the pelvis at the stage of primary diagnosis in order to determine macroscopic tissue component in the prostate bed area. To rule out regional and distant metastases, all patients underwent positron emission tomography with 18F- or 68Ga-labeled prostate-specific membrane antigen. All patients included in the study underwent perineal biopsy of the prostate bed and seminal vesicles.Results. Median follow-up in the treatment group was 35.7 (24–54) months. Overall survival was 100 %. Prostatespecific antigen-specific survival was 88.2 %. There were no local recurrences of PCa in the treatment group. In patients with local PCa recurrence, significant predictors of treatment failure were the presence of clinically extremely high risk of progression at initial diagnosis (p = 0.003), development of biochemical relapse up to 24 months after main treatment (p = 0.001), and increased blood level of prostate-specific antigen above 10 ng/mL during registration of biochemical relapse (p = 0.002).Conclusion. High-dose rate brachytherapy is a safe and effective salvage treatment for local recurrence of PCa after radical prostatectomy. In addition to the brachytherapy technique, the diagnostic stage is also of great importance providing visualization of the exact location of tumor recurrence.

Tumor-Stroma Proportion to Predict Chemoresistance in Patients With Ovarian Cancer

Platinum-based chemotherapy is the backbone of standard-of-care treatment for patients with advanced-stage, high-grade serous carcinoma (HGSC), the most common form of ovarian cancer; however, one-third of patients have or acquire chemoresistance toward platinum-based therapies. To demonstrate the utility of tumor-stroma proportion (TSP) as a predictive biomarker of chemoresistance of HGSC, progression-free survival (PFS), and overall survival (OS). This prognostic study leveraged tumors from patients with HGSC in The Cancer Genome Atlas (TCGA) cohort (1993-2013) and an independent cohort of resected clinical specimens from patients with HGSC (2004-2014) available in diagnostic and tissue microarray formats from the University of Tübingen in Germany. Data analysis was conducted from January 2021 to January 2024. Diagnosis of HGSC. Principal outcome measures were the ability of TSP to predict platinum chemoresistance, PFS, and OS. Using hematoxylin and eosin-stained slides from the Tübingen cohort (used for routine diagnostic assessment from surgical specimens) as well as tissue microarrays, representative sections of tumors for scoring of TSP were identified using previously evaluated cutoffs of 50% stroma or greater (high TSP) and less than 50% stroma (low TSP). Digitized slides from the TCGA Cohort were analyzed and scored in a similar fashion. Kaplan-Meier time-to-event functions were fit to estimate PFS and OS. The study included 103 patients (mean [SD] age, 61.6 [11.1] years) from the TCGA cohort and 192 patients (mean [SD] age at diagnosis, 63.7 [11.1] years) from the Tübingen cohort. In the TCGA cohort, there was no significant association of TSP levels with chemoresistance, PFS, or OS. However, in the Tübingen cohort, high TSP was associated with significantly shorter PFS (HR, 1.586; 95% CI, 1.093-2.302; P = .02) and OS (hazard ratio [HR], 1.867; 1.249-2.789; P = .002). Patients with chemoresistant tumors were twice as likely to have high TSP as compared to patients with chemosensitive tumors (HR, 2.861; 95% CI, 1.256-6.515; P = .01). In tissue microarrays from 185 patients from the Tübingen cohort, high TSP was again associated with significantly shorter PFS (HR, 1.675; 95% CI, 1.012-2.772 P = .04) and OS (HR, 2.491; 95% CI, 1.585-3.912; P < .001). In this prognostic study, TSP was a consistent and reproducible marker of clinical outcome measures of HGSC, including PFS, OS, and platinum chemoresistance. Accurate and cost-effective predictive biomarkers of platinum chemotherapy resistance are needed to identify patients most likely to benefit from standard treatments, and TSP can easily be implemented and integrated into prospective clinical trial design and adapted to identify patients who are least likely to benefit long-term from conventional platinum-based cytotoxic chemotherapy treatment at the time of initial diagnosis.

The effect of GnRH analog treatment on BMI in children treated for precocious puberty: a systematic review and meta-analysis.

The purpose of the present meta-analysis was to systematically evaluate the effect of GnRHa treatment on the BMI of children with precocious puberty after GnRHa treatment as compared to before, and to analyze the effect of GnRHa treatment on the body composition of children with precocious puberty at different BMIs by classifying into normal body mass, overweight, and obese groups according to BMI at the time of initial diagnosis. A meta-analysis was performed using Stata 12.0 software by searching PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), and Wan fang database for relevant literature on standard deviation score of body mass index (BMI-SDS) after GnRHa treatment as compared to before in children with precocious puberty. A total of eight studies were included with a total sample size of 715 cases, and the results of meta-analysis showed that BMI-SDS increased in children with precocious puberty after GnRHa treatment as compared to before starting [(weighted mean difference (WMD)=0.23, 95 % CI: 0.14-0.33, p=0.000)] and also increased in children with normal body mass [(WMD=0.37, 95 % CI: 0.28-0.46, p=0.000)], and there was no significant change in BMI-SDS in children in the overweight or obese group [(WMD=0.01, 95 % CI:-0.08-0.10, p=0.775)]. Overall, there was an observed increase in BMI-SDS at the conclusion of GnRHa treatment in children with precocious puberty. Additionally, it was found that the effect of GnRHa treatment on body composition varied among children with different BMI status. Clinicians should emphasize the promotion of a healthy lifestyle and personalized dietary managementfor children.

Patterns and Disparities in Recorded Gonioscopy During Initial Glaucoma Evaluations in the United States

To assess patterns in gonioscopy during initial glaucoma evaluations in the United States. Retrospective, case-control study. Patients undergoing initial glaucoma evaluation between 2009-2020 were identified in the Optum Clinformatics DataMart. Initial evaluation was defined as follows: (1) glaucoma suspect, anatomical narrow angle (ANA), or primary/secondary glaucoma diagnosed by an ophthalmologist; (2) continuously observable during a 36-month lookback period; (3) no history of glaucoma medications, laser, or surgical procedures; and (4) optical coherence tomography (OCT) or visual field performed within 6 months of initial diagnosis. Logistic regression models were developed to identify factors associated with no record of gonioscopy based on Current Procedural Terminology (CPT) codes. Among 198,995 patients, 20.4% and 29.5% had recorded gonioscopy on the day of diagnosis or within 6 months, respectively. On multivariable analysis, odds of recorded gonioscopy within 6 months of initial evaluation was lower (P < .001) among non-Hispanic Whites (OR=0.84) but similar for Blacks (OR=1.02) and Hispanics (OR=0.96) compared with Asians. Age ≥60 years (OR<0.82), pseudophakia/aphakia (OR=0.58), or residence outside of the Northeast region (OR=0.66-0.84) conferred lower odds of recorded gonioscopy (P < .001). Angle closure glaucoma (OR=0.85), secondary glaucoma (OR=0.31), or open angle glaucoma/suspect (OR=0.12/0.24, respectively) patients were less likely to have recorded gonioscopy compared to ANA patients (P < .01). More than 70% patients undergoing initial glaucoma evaluation in the United States do not have a record of gonioscopy, especially elderly, non-Hispanic White, and pseudophakic patients in non-Northeast regions. This pattern does not conform to current practice guidelines and could contribute to misdiagnosed disease and suboptimal outcomes.