Symptoms In Patients Research Articles

Outcomes Post-laparoscopic Intervention for Accessory and Cavitated Uterine Masses: A Review and a Molecular Insight.

Accessory and cavitated uterine masses (ACUM) are rare Mullerian anomalies, defined as an isolated accessory cavitated mass lined with endometrial epithelium. This article explores ACUM lesions from two aspects and integrates a case report of a successful laparoscopic-assisted intervention for ACUM in a 24-year-old woman with refractory dysmenorrhea with a review of current literature on laparoscopic surgical techniques. Unique to this case was the process of undergoing targeted genetic sequencing via the Find ITTM Panel Version 3.4 on the ACUM, looking for mutations in KRAS, PIK3CA, and FGFR2. A process that was inspired by recent reports that indicate that even normal endometrium can harbor cancer-associated mutations. A comprehensive search of Ovid MEDLINE and Embase was performed. Studies were selected if they explored laparoscopic surgery's impact on ACUM patients' outcomes related to fertility, menorrhagia, or dysmenorrhea. Risk of bias assessment was performed using the JBI Critical Appraisal Checklist. From 160 articles identified, 25 full-text articles were analyzed with a total of 75 unique patients discussed. Dysmenorrhea was present in 100% of cases (n=75/75), and laparoscopic resection improved patient symptoms in 84% (n=63/75) of cases. The mass excised in the case was positive for somatic missense mutations in RET (R813W) and HRAS (G12S) genes, identified at low variant allele frequencies. These results demonstrated that laparoscopic surgical approaches are effective and frequently the first surgical approach chosen for the treatment of ACUM, but that techniques to treat these conditions are not standardized. This case is the first to demonstrate mutations in ACUM, suggesting a potential role for cancer-associated somatic mutations in their genesis. Future developments in this area may include sending more of these samples for genetic analysis, improving our understanding of how these lesions are formed, while also working to standardize how they are removed.

Managing your Palliative Patient.

Palliative Care is the symptom management of any patient who has an irreversible, progressive, life-limiting condition and is not solely cancer patients. It aims to enhance quality of life, utilizing a holistic, multidisciplinary approach. Good symptom management of palliative patients is what every clinician should be able to deliver. This short article addresses the practical management of how to commence strong opioids, palliative surgical interventions, palliative emergencies and lastly, when do you stop treating a patient who is clinically deteriorating.

Comparison of safety and efficacy of pantoprazole alone with pantoprazole plus amitriptyline in functional dyspepsia patients: a randomized control trial

Background: The term functional dyspepsia refers to ulcer-like symptoms in patients who lack overt gastro duodenal ulceration. Functional dyspepsia can be subdivided into: postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and based on the presence of symptoms related to meals. It is defined as the presence of one or more of the following: postprandial fullness, early satiation, epigastric pain or burning, and no evidence of structural disease. Pantoprazole alone is compared with pantoprazole plus amitriptyline to relieve dyspepsia symptoms in functional dyspepsia patients. Methods: The study was a randomized, prospective, open label, comparative interventional study. The study was conducted in the Department of Pharmacology and Department of Gastroenterology and Hepatology at Dr. R.P.G.M.C. Kangra at Tanda Himachal Pradesh, India which is 700 bedded multispecialty tertiary health care from August 2023 to May 2024 and follow -up was done for 4 weeks after initiation of treatment, to compare the safety and efficacy of pantoprazole with pantoprazole plus amitriptyline in functional dyspepsia patients. Results: In our study compared to pantoprazole group, pantoprazole plus amitriptyline group has statistically significant reduction in all the 3 scores viz. Glasgow dyspepsia severity score (GDSS) (4.26±1.14 versus 3.3±1.37, p=0.002), short form leads dyspepsia questionnaire (SF-LDQ) (4 [3-5] versus 3 [2-4], p=0.005), and visual analogue pain score (VAS) (1 [1-2] versus 1 [0-1], p=0.0009). Conclusions: The combination of pantoprazole and amitriptyline was more effective than pantoprazole alone in improving symptoms of functional dyspepsia, with no significant safety concerns.

Neuroleptics used in critical COVID associated with moderate-severe dyspnea after hospital discharge

Dyspnea is a prominent symptom in patients with long COVID due to its high prevalence and significant clinical impact. However, the influence of commonly used medications in critically ill patients on long-term dyspnea remains unclear. This study aimed to identify risk factors and assess the impacts associated with moderate to severe dyspnea in COVID-19 survivors. This study evaluated patients admitted to a university hospital between April 2020 and April 2021. Data were collected on clinical preconditions, hospital and ICU stays, and the use of corticosteroids, neuroleptics, neuromuscular blockers, midazolam, fentanyl, and noradrenaline. Post-discharge evaluations were conducted at 1 and 12 months, assessing dyspnea, frailty, quality of life, functional capacity, anxiety, and depression. Descriptive statistics, including frequencies and percentages, were used, and logistic regression analysis was performed to identify factors associated with moderate to severe dyspnea at 1 and 12 months post-discharge. Statistical significance was defined as P < 0.05. A total of 100 patients were prospectively included in the study; all underwent the 1-month evaluation, and 63 completed the 12-month evaluation. Limiting dyspnea, defined as an mMRC score > 1, was observed in 56.6% of patients at 1 month and 33.9% at 12 months post-discharge. Independent factors associated with limiting dyspnea at 1 month included the total dose of neuroleptics administered during hospitalization and the presence of pre-existing comorbidities. The use of corticosteroids, neuromuscular blockers, midazolam, fentanyl, and noradrenaline showed no significant association with limiting dyspnea. Dyspnea at 1 month post-discharge was an independent risk factor for the persistence of limiting dyspnea at 12 months. Patients with limiting dyspnea at 12 months exhibited higher levels of depression, anxiety, and frailty, alongside reduced quality of life and functionality. Patients with severe COVID-19 exhibit a high prevalence of limiting dyspnea in the long term. The total dose of neuroleptics administered during hospitalization and the presence of comorbidities were independently associated with limiting dyspnea after discharge. At 12 months post-discharge, individuals with persistent limiting dyspnea frequently demonstrated additional physical and mental health impairments, underscoring the need for comprehensive evaluation and management to mitigate the burden of long-term disabilities.

Advanced Therapeutic Approaches for Metastatic Ovarian Cancer

Ovarian cancer is the fifth leading cause of cancer-related death among women, which is one of the most common gynecological cancers worldwide. Although several cytoreductive surgeries and chemotherapies have been attempted to address ovarian cancer, the disease still shows poor prognosis and survival rates due to prevalent metastasis. Peritoneal metastasis is recognized as the primary route of metastatic progression in ovarian cancer. It causes severe symptoms in patients, but it is generally difficult to detect at an early stage. Current anti-cancer therapy is insufficient to completely treat metastatic ovarian cancer due to its high rates of recurrence and resistance. Therefore, developing strategies for treating metastatic ovarian cancer requires a deeper understanding of the tumor microenvironment (TME) and the identification of effective therapeutic targets through precision oncology. Given that various signaling pathways, including TGF-β, NF-κB, and PI3K/AKT/mTOR pathways, influence cancer progression, their activity and significance can vary depending on the cancer type. In ovarian cancer, these pathways are particularly important, as they not only drive tumor progression but also impact the TME, which contributes to the metastatic potential. The TME plays a critical role in driving metastatic features in ovarian cancer through altered immunologic interactions. Recent therapeutic advances have focused on targeting these distinct features to improve treatment outcomes. Deciphering the complex interaction between signaling pathways and immune populations contributing to metastatic ovarian cancer provides an opportunity to enhance anti-cancer efficacy. Hereby, this review highlights the mechanisms of signaling pathways in metastatic ovarian cancer and immunological interactions to understand improved immunotherapy against ovarian cancer.

HLA-class II genes association with multiple sclerosis: An immunogenetic prediction among multiple sclerosis Jordanian patients.

Multiple sclerosis (MS) is an inflammatory autoimmune disease affecting the central nervous system (CNS). The pathogenesis of MS is characterized by neuronal axonal degeneration and demyelination. Among the genes that raises MS risk are the HLA-class II genes. The goals of this study were to investigate the role of the HLA-DRB1 and HLA-DQB1 genes (for the first time) in Jordanian MS patients and their association with MS disease. The association of these genes with other clinical features, such as optic neuritis, sensory impairment, and brainstem symptoms in MS patients was investigated as well using PCR-SSP techniques. Our findings indicated an association between HLA-DRB1 * 03:01 (Pc = 0.01) and HLA-DRB1 * 04:01 (Pc = 0.004) alleles with Jordanian MS patients. In addition, a significant linkage between HLA-DRB1 * 15:01 and HLA-DQB1 * 06:01 alleles (Pc ≤ 0.001 and Pc = 0.012, respectively) were presented among Jordanian MS patients with optic neuritis compared to Jordanian MS patients without optic neuritis. Moreover, HLA-DQB1 * 05:01 and HLA-DQB1 * 06:02 alleles (Pc ≤ 0.001 and Pc = 0.006, respectively) was found to be related with sensory impairment in MS patients. Additionally, HLA-DRB1 * 07:01 allele indicates a positive correlation in MS patients with brainstem symptoms (Pc < 0.001). Moreover, our results indicated that there is no association on the HLA-DRB1 ~ HLA-DQB1 haplotype level and MS disease. Knowing the genes that are linked to MS, they may facilitate MS diagnosis, prevention, and treatment at earlier stage. Also, these results may serve in the development of more potent therapeutic regimens for MS and its related complications, such as optic neuritis, sensory impairment, and brainstem symptoms.

Prevalence and clinical significance of anti-neutrophil cytoplasmic antibodies in interstitial lung disease: A retrospective cohort study.

Antineutrophil cytoplasmic antibodies (ANCAs) are occasionally positive in patients with interstitial lung disease (ILD). The positivity rates of ANCAs in various types of ILD and the role of ANCAs in ILD are still unclear. The purpose of this study was to estimate the prevalence of ANCAs in Chinese people diagnosed with ILD (including idiopathic pulmonary fibrosis) and identify differences in clinical features, radiographic features, and survival between patients with ANCA-positive and ANCA-negative ILD. We retrospectively reviewed the data of 706 ILD patients with available ANCA results from March 2010 to October 2023 at the First Affiliated Hospital of Ningbo University. Patient demographics, symptoms, laboratory parameters, chest CT, and pulmonary function testing results were collected and analysed at each patient's initial diagnosis. The prevalence and associations of ANCAs with clinical characteristics and survival were evaluated. ANCAs were positive in 158 of the 706 (22.4%) ILD patients. Compared with ANCA-negative ILD patients, ANCA-positive ILD patients tended to be older, had higher CRP and ESR levels, and had a significantly greater proportion of rheumatoid factor positivity. In total, 58.2% (92/158) of patients were ANCA-positive on average (41.6 ± 31.4) months after ILD diagnosis. Patients with ANCA-positive ILD had higher all-cause mortality than did those with ANCA-negative ILD (33.5% vs 25.0%, p = 0.033). The usual interstitial pneumonia (UIP) pattern (56.3%) was the most common chest HRCT pattern. The proportions of patients with honeycombing (p < 0.001) and oddly shaped cysts (p < 0.001) were significantly greater in the ANCA-positive ILD group than in the ANCA-negative ILD group. Acute exacerbation (AE) of ILD (HR 2.40, 95% CI 1.37-4.22, p = 0.002) was independently associated with shorter survival, and receiving glucocorticoids combined with immunosuppressants (HR 0.30, 95% CI 0.16-0.57, p < 0.001) was independently associated with longer survival in ANCA-positive ILD patients. The prevalence of ANCAs in patients with ILD is not rare, and ANCA testing in ILD patients is necessary. Oddly shaped cysts with or without a UIP pattern may be a characteristic chest imaging manifestation of ANCA-positive ILDs. The frequency of AEs in ANCA-positive ILD patients is high, and more attention should be given to ANCA-positive ILD patients who have AEs.

Detection of Gallbladder Disease Types Using a Feature Engineering-Based Developed CBIR System

Background/Objectives: Early detection and diagnosis are important when treating gallbladder (GB) diseases. Poorer clinical outcomes and increased patient symptoms may result from any error or delay in diagnosis. Many signs and symptoms, especially those related to GB diseases with similar symptoms, may be unclear. Therefore, highly qualified medical professionals should interpret and understand ultrasound images. Considering that diagnosis via ultrasound imaging can be time- and labor-consuming, it may be challenging to finance and benefit from this service in remote locations. Methods: Today, artificial intelligence (AI) techniques ranging from machine learning (ML) to deep learning (DL), especially in large datasets, can help analysts using Content-Based Image Retrieval (CBIR) systems with the early diagnosis, treatment, and recognition of diseases, and then provide effective methods for a medical diagnosis. Results: The developed model is compared with two different textural and six different Convolutional Neural Network (CNN) models accepted in the literature—the developed model combines features obtained from three different pre-trained architectures for feature extraction. The cosine method was preferred as the similarity measurement metric. Conclusions: Our proposed CBIR model achieved successful results from six other different models. The AP value obtained in the proposed model is 0.94. This value shows that our CBIR-based model can be used to detect GB diseases.

Comparison of recognition of symptom burden in MPN between patient- and physician-reported assessment - an intraindividual analysis by the German Study Group for MPN (GSG-MPN).

Myeloproliferative neoplasms (MPN) are associated with a variety of symptoms that severely impact patients' quality of life and ability to perform daily activities. Recent studies showed differences in the perception of physician- versus patient-reported symptom burden. However, studies directly comparing patient- and physician-reported ratings are lacking. Here, a retrospective analysis on symptom burden of 3979 MPN patients of the Bioregistry of the German Study Group for MPN was conducted to intra-individually compare physician and patient reports collected at the same time. Cohen's kappa was calculated to assess the degree of agreement between patient and physician reports. Factors influencing baseline symptom severity were identified using linear regression and adjusted Cox models were calculated to investigate the effect of symptom burden on survival. MPN patients had a high symptom burden, which neither decreased over time nor upon cytoreductive therapy. All symptoms were more frequently reported by patients compared to physicians. Agreement remained low and only slightly improved when considering a higher threshold for patient symptom severity. Patients with severe symptom burden had inferior survival compared to patients with less severe symptoms. Assessment of symptom burden in MPN is therefore insufficient and patient-reported outcome tools need to be implemented into clinical routine.

Evaluating the impact of high-dose vitamin D3, vitamin C, vitamin E, and zinc supplementation on inflammatory cytokines, lesion severity, and symptom management in hidradenitis suppurativa

This integrative, holistic review critically evaluates the impact of high-dose vitamin D3, vitamin C, vitamin E, and zinc supplementation on inflammatory cytokine levels, lesion severity, and symptom management in patients with hidradenitis suppurativa (HS). By integrating data from recent clinical trials and observational studies, we explore how these supplements influence key aspects of HS pathology. High-dose vitamin D3 has been shown to significantly reduce levels of inflammatory cytokines and decrease lesion severity, suggesting its role in modulating immune responses and improving disease outcomes. Similarly, the antioxidant properties of vitamins C and E are assessed for their ability to reduce oxidative stress and inflammation, which may lead to improved symptom management and reduced severity of HS lesions. Zinc supplementation, particularly in the form of zinc sulfate, is examined for its effects on enhancing skin barrier function and decreasing the frequency of disease flares. Collectively, these nutritional interventions may offer a multifaceted approach to HS management, highlighting the potential for combining these supplements to optimize therapeutic outcomes. The findings underscore the need for further research to determine the optimal dosing, duration, and interaction of these supplements with standard HS treatments to establish comprehensive management protocols.

Higher Occurrence of Ocular Surface Disease Symptoms in Patients with Atopic Dermatitis: Data from 57,464 Subjects in the FOREVER Cohort.

Background: Ocular comorbidity in atopic dermatitis (AD) is known, but ocular surface disease (OSD) symptoms do not always result in a physiciańs diagnosis. Objective: To investigate the occurrence of OSD symptoms and self-reported vision and health in a general population and explore their association with AD. Methods: A cross-sectional questionnaire study using the nationwide population-based FOREVER cohort of Danish adults. The occurrence of OSD symptoms, self-reported vision and health, and their association with AD were investigated using logistic regression models. Results: A total of 57,464 (85%) out of 67,178 participants completed the questionnaire. 1,298 had current AD, 5,198 had a history of AD, and 50,968 never had AD. The occurrence of one or more OSD symptoms was associated with both current (adjusted odds ratio, 1.19; 95% confidence interval, 1.05-1.34; P = 0.006) and previous AD (1.16; 1.09-1.23; P < 0.001), compared to those who never had AD, after adjusting for age, sex, smoking status, and atopic comorbidities (asthma and rhinitis). Participants with current and previous AD also rated their overall health "worse" (1.29; 1.16-1.43; P < 0.001) (1.12; 1.06-1.18; P < 0.001), compared to those who never had AD. Conclusions: The occurrence of OSD symptoms and worse self-rated vision and health are associated with AD in a general population.

Detailed investigation of the levodopa response rates in distinct motor subscores in Parkinson's disease patients with and without STN-DBS.

To investigate the levodopa response (LDR) in a detailed manner in Parkinson's disease (PD) patients with and without STN-DBS. In this respect, we sought to evaluate the effect of LDR on distinct motor symptoms one by one. The data of all consecutive PD patients who visited our movement disorders outpatient clinics at Etlik City Hospital between January 2023 and January 2024 were retrospectively evaluated. We enrolled patients whose full clinical assessments were available. The LDR was evaluated according to a previously described method. We included 194 PD patients in this study [49 STN-DBS (+) patients, 145 STN-DBS (-) patients]. The disease duration was greater in the STN-DBS group, as expected (12 y, 5 y, p = 0.00). The LDR ratios for the total score and subitem scores of the MDS-UPDRS-3 were similar between the patient groups. All the subscores of the MDS-UPDRS-3 were significantly lower for the 'ON' medication state than for the 'OFF' medication state in both patient groups. We demonstrated similar LDR rates for all motor subitems in patients with and without STN-DBS in a detailed manner. Our findings demonstrate the benefit of dopaminergic treatment on distinct motor symptoms in patients with STN-DBS.

An Innovative Surgical Technique: Anchoring Levonorgestrel-Releasing Intrauterine System Using a Specialized Fixation Needle

Background: Numerous surgical techniques have been proposed to enhance the stability of intrauterine system (IUS) and reduce the incidence of displacement and expulsion, however, challenges remain. We aim to explore improved therapeutic strategies for levonorgestrel-releasing intrauterine system (LNG-IUS) displacement or expulsion cases. Methods: This study proposes a novel method utilizing a specialized fixation needle to anchor the Mirena intrauterine device (IUD) within the uterine muscle layer. From June 2022 to December 2022, patients underwent hysteroscopic suturing for Mirena fixation, serving as the control group. From January 2023 to June 2023, 38 patients underwent hysteroscopic anchoring of Mirena using a specialized fixation needle, constituting the experimental group. Results: A total of 59 patients were included in the study. The experimental group included 38 patients, aged 31 to 51 years, with a median age of 41.5 (interquartile range: 36, 46) years. Comparison of treatment outcomes between the two groups showed significant improvements in Visual Analog Scale (VAS) scores, Pictorial Blood Assessment Chart (PBAC) scores, and hemoglobin (Hb) levels after treatment in both the experimental and control groups (all p &lt; 0.001). Moreover, in the control group, 90.48% (19/21) of patients had normal contraceptive device positions during postoperative follow-up. In the control group, 2 patients (9.52%) experienced IUD displacement postoperatively. While, in the experimental group, 97.37% (37/38) of patients had normal contraceptive device positions during postoperative follow-up. However, 2.63% (1/38) experienced sudden excessive menstrual bleeding and IUD expulsion at 3 months postoperatively, requiring total hysterectomy. Conclusions: Hysteroscopic anchoring of the LNG-IUSs using a specialized fixation needle addresses the issue of device expulsion, offering a more straightforward and accessible alternative to traditional hysteroscopic suturing methods. Moreover, similar to hysteroscopic suturing of Mirena, this technique effectively relieves dysmenorrhea and heavy menstrual bleeding symptoms in patients.

Plaque shift to the brachiocephalic artery after subclavian artery stenting: illustrative case.

Subclavian artery stenosis (SAS) has a prevalence of 1.9% in the general United States population. Revascularization, often by stenting, is indicated for symptomatic patients. Plaque shift (PS) is a well-known poststenting complication in coronary interventions but has not been reported in subclavian artery (SA) stenting. This case report documents the occurrence of PS after stenting for SAS, highlighting a rare but significant complication. An 87-year-old woman with a history of hypertension and dyslipidemia presented with right upper-limb pain and fatigue. Imaging confirmed stenosis with calcified plaque at the origin of the right SA. Following endovascular stenting under local anesthesia, imaging revealed PS to the brachiocephalic artery (BA). To prevent migration into the common carotid artery (CCA), a dual-layer stent was placed from the CCA to the BA. The patient's symptoms resolved, and follow-up confirmed successful plaque stabilization without restenosis 1 year postprocedure. Even apparently hard SA plaque with calcification can result in PS with stenting. When PS occurs, prompt stenting can prevent cerebral embolism. https://thejns.org/doi/10.3171/CASE24760.

Synergic Efficacy of a Multicomponent Nutraceutical Add-On Therapy in Seasonal Allergic Rhinitis in Children: A Prospective, Randomized, Parallel-Group Study

Background: Emerging evidence suggests that nutraceuticals, alongside standard therapy, may benefit children with allergic rhinitis (AR). This study aimed to compare the efficacy of Quertal® (Neopharmed Gentili S.p.A., Milano, Italy), a nutraceutical supplement based on Perilla frutescens, Quercetin, and vitamin D3, combined antihistamines per os versus antihistamines alone, in improving AR symptoms considering respiratory functional and laboratory biomarkers in pediatric age. Materials and Method: This study included 100 children, 50 in the case group (Quertal® plus antihistamines) and 50 in the control group (antihistamines alone), with mild/moderate AR sensitized to grass pollens. They underwent assessments of respiratory function (rhinomanometry-AAR, spirometry), inflammation markers (Nasal Nitric Oxide [nFeNO]; exhaled Nitric Oxide [eFeNO]; nasal cytology), and laboratory assays (blood eosinophils, total IgE and specific IgE to Phl p1). Results: After three months of treatment, the case group showed statistically significant improvement in nFeNO and eFeNO values compared to controls (p &lt; 0.001), as well as a reduction in nasal eosinophils (p &lt; 0.001). Conclusions: Adding Quertal® to standard antihistamine therapy may reduce nasal inflammation and improve AR symptoms in pediatric patients. This combination therapy shows promise as a practical, well-tolerated approach to managing AR and may have broader implications for enhancing long-term outcomes.

Low doses of cannabis extract ameliorate non-motor symptoms of Parkinson's disease patients: a case series.

IntroductionParkinson’s disease (PD) is mainly characterized by motor symptoms including muscle rigidity, resting tremor and bradykinesia. However, the management of the non-motor symptoms represent a relevant clinical challenger in PD. These non-motor symptoms include cognitive and sleep disturbance and there is evidence that cannabinoids may represent alternative and effective treatments for non-motor symptoms of PD.MethodsTherefore, this study addressed the effects of oral treatment with cannabis extract on cognition, insomnia, and daytime sleepiness in six patients with moderate PD. The patients were randomized to receive two different doses of a cannabis extract: THC:CBD 250:28 μg/day (n = 3) or 1000:112 μg/day (n = 3). The assessment of cannabis administration related to the cognitive field was measured by the Montreal Cognitive Assessment test (MoCA test), the insomnia was assessed by the Insomnia Severity Index (ISI), and daytime sleepiness was assessed using the Epworth sleepiness scale (ESS). All clinical evaluations were performed before treatment and at 15, 30, 60, and 90 days of treatment.ResultsThe statistical analysis indicated a significant benefit of the cannabis extract treatment, at dose of 1000:112 μg/day after 60 days of treatment, on insomnia assessed by ISI. Moreover, the statistical analysis of data from ISI and MoCA tests showed a trend toward improvement over time, while no significant effect was observed in the ESS. There were no reports of significant adverse effects during the cannabis extract treatment.DiscussionThese results demonstrate benefits of short-time treatment (60 days) with low doses of cannabis extract on insomnia in PD patients. This study provide novel findings of the potential of combining CBD and THC as safe and effective treatments for non-motor symptoms of PD.

Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer Patients

Background: Aromatase inhibitors-related musculoskeletal syndrome (AIMSS) is a common side effect experienced by early breast cancer patients undergoing endocrine therapy. This condition can result in medication discontinuation and a diminished quality of life. The objective of this study was to characterize AIMSS, investigate its pathogenesis, and identify potential biomarkers at both the protein and metabolic levels. Methods: We collected peripheral blood samples from 60 women diagnosed with breast cancer undergoing aromatase inhibitor therapy, of whom 30 had AIMSS and 30 did not. The samples were analyzed using four-dimensional data-independent acquisition (DIA)-based proteomics and untargeted metabolomics, employing liquid chromatography–mass spectrometry (LC–MS) on the latest platform. Results: The mean age of participants was 49.2 (11.3) years in the AIMSS group and 50.1 (11.5) years in the non-AIMSS group. There were no statistically significant differences between the two groups in terms of age, BMI, education level, clinical stage, and treatment. In total, we identified 3473 proteins and 1247 metabolites in the samples. The chemokine signaling pathway (p = 0.015), cytokine–cytokine receptor interaction (p = 0.015), complement and coagulation cascades (p = 0.004), neuroactive ligand–receptor interaction (p = 0.004), and the estrogen signaling pathway (p = 0.004) were significant enriched in differentially expressed proteins (DEPs). GnRH secretion (p &lt; 0.001), sphingolipid signaling pathways (p &lt; 0.001), endocrine resistance (p &lt; 0.001), the estrogen signaling pathway (p = 0.001), endocrine and other factor-regulated calcium reabsorption (p = 0.001), dopaminergic synapse (p = 0.003), regulation of lipolysis in adipocytes (p = 0.004), biosynthesis of cofactors (p = 0.004), thyroid hormone synthesis (p = 0.008), aldosterone synthesis and secretion (p = 0.001), taurine and hypotaurine metabolism (p = 0.011), ovarian steroidogenesis (p = 0.011), and the cAMP signaling pathway (p = 0.011) were significantly enriched in differentially expressed metabolites (DEMs). Complement C3 (p = 0.004), platelet factor 4 (p = 0.015), KRT10 (p = 0.004), KRT14 (p = 0.004), beta-estradiol (p = 0.019), testosterone (p = 0.023), sphingosine (p &lt; 0.001), and 1-stearoyl-2-arachidonoyl-sn-glycerol (p = 0.039) could be the monitoring and therapeutic targets for AIMSS. Conclusions: This study offered new insights into the mechanisms underlying musculoskeletal symptoms associated with aromatase inhibitors. It also highlighted potential biomarkers for predicting and addressing these symptoms in breast cancer patients, paving the way for improved intervention strategies.

Abstract A061: Discovery of resilient T cells from patients in responses to combination immunotherapy and their metabolic features

Abstract Salvage combination therapy including radiotherapy and immunotherapy has been used to reduce tumor burden and tumor-related symptoms in patients with advanced cancer that is refractory to ICI monotherapy. Among those patients who experienced significant tumor regression in responses to combination therapy, we identified a rebound of effector CD8+ T cells with high cytotoxic capacity and metabolic fitness. We use the term T cell resilience to explain the rebound of cytotoxic CD8+ T cells in response to combination therapy and examine the underlying mechanisms of T cell resilience. Resilient T cells are enriched in CX3CR1+ CD8+ T cells with low mitochondrial membrane potential, accumulate less reactive oxygen species (ROS), and express more malic enzyme 1 (ME1). We found ME1 overexpression enhanced the cytotoxicity and expansion of effector CD8+ T cells partially via the type I interferon pathway. ME1 also increased mitochondrial respiration while maintaining the redox state balance. Importantly, ME1 increased the cytotoxicity of peripheral lymphocytes from patients with advanced cancers and improve the efficacy of tumor-infiltrating lymphocytes (TIL) therapy in animal models. Our results demonstrate the presence of resilient T cells in patients, suggest that T cell resiliency is attributed to their metabolic reprogram mediated by ME1, which is a new T cell-intrinsic therapeutic target for T cell-based immunotherapy. Citation Format: Haidong Dong, Joanina K Gicobi. Discovery of resilient T cells from patients in responses to combination immunotherapy and their metabolic features [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A061.

Identification and Validation of Key Amino Acids in IgE Linear Epitopes of β-Lactoglobulin: Comparison of Recognition Patterns of Chinese Bovine Milk-Allergic Sera with Different Symptoms.

β-lactoglobulin (BLG) is the primary allergen in bovine milk allergy. The identification of key amino acids in the BLG epitopes has not been comprehensive due to differences in identification methods, patient symptoms, and population characteristics. In this study, bioinformatics predictions were conducted for key amino acids based on two potential IgE linear epitopes in BLG. Then, the peptide AA30-43 was confirmed as an IgE linear epitope through alanine scanning mutagenesis and peptide microarray assays, with four key amino acids (A34, A37, R40, and V41) common to different symptoms being identified. Moreover, symptom-specific key amino acids were identified. Serine (S30) and aspartic acid (D33) are the key amino acids for cutaneous allergy, while food allergy sera showed a preference for recognizing leucines in different positions (L31 and L39). Additionally, mutant peptides (R40, V41, L39, and D33) showed an obvious decrease in digestive stability compared with the epitope. Finally, the results of the KU812 cell degranulation model validated the critical role of the amino acids in allergenicity. These findings offer significant advantages for advancing both immune tolerance therapies and hypoallergenic milk product development, which hold significant implications for further research, prevention, and treatment of bovine milk allergy.

MALFORMAÇÕES DA VIA BILIAR: RELATO DE CASO DE CISTO DE COLÉDOCO

Introduction: Biliary cysts, also known as choledochal malformations, are cystic dilations that can occur in isolation or in multiple segments of the biliary tree. Clinically, they often manifest with abdominal pain and jaundice, although some patients remain asymptomatic. Case Report: We present the case of a 30-year-old female patient from the interior of the state of Amazonas, with hearing loss and a history of previous cholecystectomy. The patient was diagnosed with a choledochal cyst after a suggestive clinical picture, confirmed by imaging tests. Treatment consisted of resection of the cyst and reconstruction using a Roux-en-Y biliodigestive anastomosis. Discussion: Choledochal cysts are rare conditions, especially because they can be asymptomatic, which can delay diagnosis. Surgical resection is essential both to reduce the risk of malignization and to relieve symptoms in symptomatic patients. Conclusion: With advances in imaging tests, the diagnosis of choledochal cysts has become more frequent. However, this condition remains relatively rare in clinical practice. Surgical treatment by resection is recommended due to the risk of malignant transformation, with Roux-en-Y biliodigestive anastomosis being the preferred technique for reconstruction.