Clinical Prognosis Research Articles

Long-term survival after conversion surgery for an esophageal neuroendocrine carcinoma: a case report

BackgroundEsophageal neuroendocrine carcinomas (NECs) are extremely rare. Published information on their clinical features, pathological findings, and prognosis is lacking. The optimal treatment for esophageal NECs has not yet been determined because they appear extremely malignant histologically and have a poor prognosis. We here report on a patient with an esophageal NEC who was successfully treated with multidisciplinary therapies.Case presentationThe patient, a 47-year-old man, was admitted to our hospital with dysphagia and weight loss and an ECOG performance status of 3–4. Upper endoscopy showed a large circumferential neoplasm at the esophagogastric junction. Computed tomography showed lymph node metastases around the left gastric artery. Echocardiography raised a suspicion of invasion of the left atrium. Histopathological examination of biopsy tissue revealed diffuse proliferation of small atypical cells resembling naked nuclei with extensive necrosis and degeneration. The cells showed positive staining for CD56, chromogranin A, and synaptophysin on immunohistochemical analysis. Ki67 was positive in over 90% of cells. He was diagnosed with an esophageal NEC that had infiltrated the left atrium; his cancer was therefore inoperable. Because of his poor overall condition, palliative radiotherapy (30 Gy in 15 fractions) was administered, accompanied by nutritional management. This was followed by four courses of chemotherapy with carboplatin plus etoposide, after which the primary tumor and locoregional lymph node metastases were found to have shrunk. Thoracoscopic- and laparoscopic-assisted McKeown esophagectomy were performed. The postoperative pathological diagnosis was NEC pT3pN0M0 Stage II. The patient had a good postoperative course and received two courses of postoperative adjuvant chemotherapy (carboplatin plus etoposide). Currently, 3 years after commencing treatment, there is no evidence of recurrence.ConclusionsAs mentioned above, there is no established treatment regime for esophageal NEC, and the benefits of conversion surgery are unknown. Our patient achieved long-term recurrence-free survival after radiation therapy, chemotherapy, and surgery for an esophageal NEC with left atrial invasion and multiple lymph node metastases. Conversion surgery for esophageal NECs that respond to chemotherapy may contribute to long-term survival.

Mitochondrial DNA in bronchoalveolar lavage fluid is associated with the prognosis of idiopathic pulmonary fibrosis: a single cohort study

BackgroundExtracellular mitochondrial DNA (mtDNA) is released from damaged cells and increases in the serum and bronchoalveolar lavage fluid (BALF) of idiopathic pulmonary fibrosis (IPF) patients. While increased levels of serum mtDNA have been reported to be linked to disease progression and the future development of acute exacerbation (AE) of IPF (AE-IPF), the clinical significance of mtDNA in BALF (BALF-mtDNA) remains unclear. We investigated the relationships between BALF-mtDNA levels and other clinical variables and prognosis in IPF.MethodsExtracellular mtDNA levels in BALF samples collected from IPF patients were determined using droplet-digital PCR. Levels of extracellular nucleolar DNA in BALF (BALF-nucDNA) were also determined as a marker for simple cell collapse. Patient characteristics and survival information were retrospectively reviewed.ResultsmtDNA levels in serum and BALF did not correlate with each other. In 27 patients with paired BALF samples obtained in a stable state and at the time of AE diagnosis, BALF-mtDNA levels were significantly increased at the time of AE. Elevated BALF-mtDNA levels were associated with inflammation or disordered pulmonary function in a stable state (n = 90), while being associated with age and BALF-neutrophils at the time of AE (n = 38). BALF-mtDNA ≥ 4234.3 copies/µL in a stable state (median survival time (MST): 42.4 vs. 79.6 months, p < 0.001) and ≥ 11,194.3 copies/µL at the time of AE (MST: 2.6 vs. 20.0 months, p = 0.03) were associated with shorter survival after BALF collection, even after adjusting for other known prognostic factors. On the other hand, BALF-nucDNA showed different trends in correlation with other clinical variables and did not show any significant association with survival time.ConclusionsElevated BALF-mtDNA was associated with a poor prognosis in both IPF and AE-IPF. Of note, at the time of AE, it sharply distinguished survivors from non-survivors. Given the trends shown by analyses for BALF-nucDNA, the elevation of BALF-mtDNA might not simply reflect the impact of cell collapse. Further studies are required to explore the underlying mechanisms and clinical applications of BALF-mtDNA in IPF.

Pediatric Takotsubo cardiomyopathy: a review and insights from a national multicentric registry

Abstract Funding Acknowledgements None. Background Takotsubo syndrome (TTS) in the pediatric population is an infrequent but relevant cause of morbidity and mortality, with limited studies addressing its clinical course and prognosis. Objectives We aimed to analyze the clinical features and prognosis of pediatric TTS in a nation-wide multicenter registry and considering the published literature. Methods we included a total of 54 patients from 4 different hospitals in Spain, as well as pediatric TTS patients from the published literature. Comparisons between groups were performed in order to assess for statistically and clinically relevant prognostic differences between pediatric and adult population features. Results Comparison between the RETAKO general population is detailed in Table 1. Pediatric patients with TTS had a median age of 11 years (IQR = 4-14). When compared to the RETAKO general population, they were more often male (51.9% vs 23.3%, p&amp;lt;0.001), and displayed a higher prevalence of secondary forms (90.7% vs 35.6% in adults, p&amp;lt;0.001). Regarding race, 11 cases (20.4%) were from Asia and 42 (77.8%) were Caucasian; whereas in RETAKO 1420 (94.9%) were Caucasians, with under 5 cases (&amp;lt;0.1%) being Asian. Pediatric patients presented less commonly with angina (11.1% vs 64.1%, p&amp;lt;0.001) or dyspnea (30% vs 41.7%, p&amp;lt;0.001), compared to the general RETAKO cohort. Nevertheless, pediatric patients with TTS exhibited a higher Killip status on admission (Killip IV 74.1% vs 10.5%, p&amp;lt;0.001), and higher needs of vasoactive and mechanical ventilatory support during hospitalization. Regarding complementary exams, pediatric patients presented with lower LVEF on admission (30.5+10.4 vs 36.9+16.9, p = 0.014) together with greater prevalence of atypical (basal or midventricular) TTS patterns on echocardiography (30.2% vs 15.8%, p = 0.006). Additionally, there were significantly less ST-segment alterations in the pediatric population (either ST-segment elevation or depression), without differences on T wave inversion in the admission ECG. During follow-up, all-cause deaths (11.1% vs 12,5%, p = 0.761) and TTS recurrences (3.8% vs 3,8%, p = 0.863) were similar between groups. Conclusions TTS in the pediatric population presents a distinctive clinical profile, with higher prevalence of atypical symptoms and physical triggers; as well as higher rates of cardiogenic shock on admission and similar mortality and recurrence rates than those of the adult population. This study provides valuable insights into understanding pediatric TTS and underscored the necessity for further research in this age group.Table 1

Lymph node or lymphoid aggregate? Impact on cancer resection quality, clinical prognosis, and tumor staging.

The clinical outcome of most cancer patients depends on the stage of the primary tumor, the lymph node status, and if distant metastases are present. According to the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), the Tumor Node Metastasis (TNM) classification of malignant tumors requires the examination of a minimum number of regional lymph nodes for each type of cancer to fulfill the criteria of high-quality surgical oncology. Due to the daily challenge of collecting an appropriate number of lymph nodes and time constraints when processing and assessing tissue samples, pathologists may be tempted to identify every histological lymphoid structure mimicking a lymph node as a "true" lymph node. Faced with this issue, we propose to resolve it by specifying histological characteristics to differentiate lymphoid aggregates from "true" lymph nodes. To find a minimum consensus, we suggest defining as lymph nodes only those lymphoid structures composed of lymphoid cells encapsulated by a complete or incomplete fibrous capsule.

Clinical characteristics and prognosis of patients with infective endocarditis admitted to a coronary unit in a hospital with cardiac surgery

Abstract Funding Acknowledgements None. Introduction Cardiac critical care units are essential for the management of complicated infective endocarditis (IE). Objective We set out to analyze the baseline characteristics, clinical complications and prognosis of patients with IE admitted to a Coronary Care Unit (CCU), as well as to compare them with patients admitted to hospital wards. Material and Methods Prospective, single-centre, observational study including patients who were diagnosed of IE from 2016-2022 and admitted in a hospital with cardiac surgery. They were classified into two groups according to whether or not they were admitted to the CCU. We collected data on microbiological isolation, cardiac and systemic complications as well as in-hospital mortality. Patients were followed long-term for cardiovascular (CV) and all-cause mortality, readmission and IE recurrence. All variables (qualitative) were compared by Chi-square test and overall mortality was compared in both groups by the LogRank test. We established a significance level of p&amp;lt;0.05. Results From a total of 162 patients with a median age of 68 years (IQR 68), 28.4% (46) were admitted to the CCU. These patients were similar in age to those not admitted (mean 65 vs 66 years, NS), but had a higher percentage of diabetics (47.8 vs 27.6%, p=0.01). The most frequent previous heart disease in both groups was valvular heart disease. The most frequently isolated microorganisms in CCU patients were Staphylococcus aureus (46.4%) and Streptococcus epidermidis (37.9%) which, in our series, produced the highest percentage of shock (35.7% and 23.3% respectively) in a statistically significant way (p&amp;lt;0.01), with the need for noradrenaline (60.9%) and dobutamine (28.3%); no ventricular assist devices were used. Critically ill patients had a higher incidence of atrioventricular block requiring a permanent pacemaker (32.6% vs 4.3%, p&amp;lt;0.01), valve dysfunction (76.1% vs 55.2%, p=0.014) and were more frequently operated than those admitted to the ward (56.%% vs 38%, p=0.04). Among all IE patients, 24.6% died during admission, most of them (15.7% of the total) were admitted to the coronary unit (p&amp;lt;0.01). In our 36-month mean follow-up, we found significantly higher readmission rates in the CCU group (36.6% vs. 15%, p&amp;lt;0.01), unrelated to IE recurrences. The critically ill group exhibited a higher mortality rate due to cardiovascular disease and all-cause causes (43.5% vs 15.9%, p0.01; 63% vs 23.9%, p0.01). In the CCU group there is significantly lower survival (mean 65 vs 37 months, LogRank p&amp;lt;0.01) with respect to the hospital ward group. Conclusion Our CCU is responsible for treating patients with IE that is highly complex and that progresses poorly, with a higher frequency of shock and in-hospital mortality, which leads to a decreased prognosis during follow-up. Anticipating complications and collaborating with cardiac surgery is essential to improve clinical outcomes.

Non-intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses: an analysis of clinical characteristics and prognosis

Non-intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses: an analysis of clinical characteristics and prognosis

Out of hospital sudden cardiac arrest as a prognostic factor for in-hospital mortality in patients admitted with cardiogenic shock

Abstract Funding Acknowledgements None. Background The mortality in cardiogenic shock (CS) is still high despite new comprehensive therapies. Cardiac arrest (CA) frequently complicates CS which can have an unfavourable effect on the course after admission. Purpose The study aimed to analyse the clinical characteristics and prognosis of patients admitted with CS after out-of-hospital cardiac arrest (OHCA) compared to the group without OHCA. Methods The studied group consisted of a total of 80 patients with an average age of 62 ± 13 years (81 % male) admitted to tertiary hospital with CS in the period 2021-2022. The severity of the shock according to the Society for Cardiac Angiography and Interventions (SCAI) SHOCK classification among the whole population was from C to E: 7 (9%), 38 (48%), and 35 (43%), respectively. The cohort was divided into 2 subgroups: the OHCA group consisted of 23 individuals (29%) and the without OHCA (non-OHCA group) consisted of 57 individuals. Results The groups did not differ in terms of demographic parameters and comorbidities. There were no differences in baseline heart rate 95 [50;114] vs. 91 [77;105] beats per minute and mean artery pressure 75 [70;97] vs. 82 [70;97] mmHg for OHCA vs. non-OHCA, respectively, all p&amp;gt; 0.05. Patients from OHCA group had higher baseline creatinine level 1.65 [1.35;1.88] vs. 1.37 [1.08; 1.65] mg/dL, p=0.019, white blood cell count 12 [9;16] vs. 17 [12;23] × 109/L, p=0.015 and lower pH from blood gas analysis 7.0 [6.9;7.2] vs. 7.3 [7.2;7.4], p&amp;lt;0.001). In the OHCA group, 90% of cases of CS were caused by acute coronary syndrome (ACS), while in the group without OHCA, 76% were due to ACS and 20 % due to the progression of chronic heart failure, p=0.032. Mechanical Circulatory Support (MCS) was used in almost every patient (98% non-OHCA vs. 95% OHCA), however, the OHCA group was more often treated with V-A ECMO 14 (64%) vs. 16 (28%) in the non-OHCA, p=0.004. The overall number of in-hospital deaths was 57 (71%). The OHCA group had significantly higher in-hospital mortality 22 (96%) compared to the non-OHCA patients 35 (61%), p=0.002. Conclusion Patients experiencing CS complicated by OHCA have more often ischaemic ethology of shock, have a greater degree of organ damage and a lower pH in blood gas analysis at admission, and have extremely high in-hospital mortality rates when compared with patients facing CS but without prior OHCA, which underscores the urgent need for improved prevention methods, interventions, and public awareness.

MINOCA, experience of a single tertiary center with a high volume of ACS

Abstract Funding Acknowledgements None. Introduction Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical entity for which there is limited evidence regarding the clinical data and prognosis. Purpose To evaluate epidemiological and clinical characteristics as well as short-term outcomes of patients with MINOCA presented at a university hospital center with high volume percutaneous coronary intervention (PCI). Methods We evaluated 1035 consecutive patients admitted to our hospital with acute myocardial infarction from June 2022 to January 2023 who underwent invasive evaluation. In-hospital and follow-up data after 30 and 90 days were collected. Primary endpoint was occurrence of a major adverse cardiovascular and cerebrovascular event (composite of cardiovascular death, cerebrovascular accident, re-hospitalization for non-fatal myocardial infarction, re-hospitalization for heart failure, malignant ventricular arrhythmia). Secondary endpoints were improvement in left ventricular ejection fraction and angina status at 30 and 90 days follow-up. Results Among patients presented with acute myocardial infarction, 8.5% (88 patients) were diagnosed with MINOCA. Mean age was 60.9 years and 61.4% were females. Arterial hypertension was present in 86.4%, hypercholesterolemia in 38.6%, diabetes in 12.5% of the patients. Smokers were 29.5% of them. During hospitalization 14.7% had a major adverse cardiovascular event, cardiovascular death occurred in 1.1%, cerebrovascular accident in 1.1%, acute heart failure in 12.5% and malignant ventricular arrhythmia in 1.1%. Primary endpoint at 30 and 90 days follow-up occurred in 10.3% and 13.7% respectively. At 30 days follow-up there was no cardiovascular death, cerebrovascular accident or malignant ventricular arrhythmia; re-hospitalization for MI was 5.7% and re-hospitalization for heart failure was 4.6%. At 90 days follow-up there was no cardiovascular death, cerebrovascular accident or malignant ventricular arrhythmia; re-hospitalization for MI occurred in 8%, re-hospitalization for heart failure in 5.7%. In regard to secondary endpoints, 24.1% experienced angina, while at 30 days and 90 days follow, 66.7% and 72.2% respectively had improvement of left ventricle EF. Conclusions In our study we found a high incidence of MINOCA affecting more frequently female patients. Angina at short term follow up was frequently recorded among out study population.

STEMI in young patients: what are we dealing with?

Abstract Funding Acknowledgements None. Background/Introduction Acute Myocardial Infarction with ST-segment Elevation (STEMI) in young adults is infrequent, with an incidence ranging from 2-12%. Our objective is to analyse the clinical characteristics, management, and prognosis of patients aged 45 years or younger with STEMI activation. Methods We conducted a retrospective review of the "Code Infarct" registry at our hospital from January 2020 to March 2023. Out of the 867 codes, 51 patients aged 45 or younger were selected. We studied clinical, angiographic, and echocardiographic parameters. Results Table 1 presents the baseline and clinical characteristics of the patients. The median time from symptom onset to the first medical contact was 126 (30-160) minutes, and the median ischemic time was 226 (122-270) minutes. Figure 1 displays the angiographic findings. Atherothrombotic disease was responsible in 78.4% of patients, with 75% of them having single-vessel coronary disease with similar involvement of the right and anterior descending coronary arteries. Five patients (9.8%) experienced spontaneous dissection, with the majority being women (80%). In 5 cases (9.8%), coronary arteries were found to be normal. The second most commonly used antiplatelet agent was prasugrel (64.7%). Fibrinolysis was performed in 5 patients (9.8%). Only 3 patients (5.9%) required inotropic/vasopressor therapy, and 2 (3.9%) received intra-aortic balloon counterpulsation. The most common complication during hospitalization was the occurrence of tachyarrhythmias (27.4%), followed by heart failure (7.8%). At discharge, 52.9% had a left ventricular ejection fraction (LVEF) &amp;gt;55%, 49.3% had LVEF between 40-55%, and only 7.8% had LVEF &amp;lt;40%. The median length of hospital stay was 5.7 (3-6) days, and there were no in-hospital deaths. One-year survival was 98%. Conclusions Atherothrombotic disease is the leading cause of STEMI in individuals aged 45 or younger in our population. Smoking and dyslipidaemia are the most prevalent risk factors. Ischemic time is longer than desired in this group, mainly due to a delay from symptom onset to initial medical contact. Promoting primary prevention and raising awareness about the clinical signs and importance of early diagnosis in STEMI could help reduce ischemic time in this population.Characteristics and Clinical PresentatioCoronary angiography findings.

SMYD2 induced PGC1α methylation promotes stemness maintenance of glioblastoma stem cells

Abstract Background The high fatality rate of glioblastoma (GBM) is attributed to glioblastoma stem cells (GSCs), which exhibit heterogeneity and therapeutic resistance. Metabolic plasticity of mitochondria is the hallmark of GSCs. Targeting mitochondrial biogenesis of GSCs is crucial for improving clinical prognosis in GBM patients. Methods SMYD2-induced PGC1α methylation and followed nuclear export is confirmed by co-immunoprecipitation, cellular fractionation, and immunofluorescence. The effects of SMYD2/PGC1α/CRM1 axis on GSCs mitochondrial biogenesis is validated by OCR, ECAR and intracranial glioma model. Results PGC1α methylation causes disabled mitochondrial function to maintain the stemness, thereby enhancing radio-resistance of GSCs. SMYD2 drives PGC1α K224 methylation (K224me), which is essential for promoting the stem-like characteristics of GSCs. PGC1α K224me is preferred binding with CRM1, accelerating PGC1α nuclear export and subsequent dysfunction. Targeting PGC1α methylation exhibits significant radiotherapeutic efficacy and prolongs patient survival. Conclusions These findings unveil a novel regulatory pathway involving mitochondria that governs stemness in GSCs, thereby emphasizing promising therapeutic strategies targeting PGC1α and mitochondria for the treatment of GBM.

Correlation Between Basal Metabolic Rate and Clinical Outcomes in Gastric Cancer Patients: A Retrospective Study

Objectives Hypermetabolism is associated with clinical prognosis of cancer patients. The aim of this study was to explore the association between basal metabolic rate (BMR) and postoperative clinical outcomes in gastric cancer patients. Methods We collected data of 958 gastric cancer patients admitted at our center from June 2014 to December 2018. The optimal cutoff value of BMR (BMR ≤1149 kcal/day) was obtained using the X-tile plot. Logistic and Cox regression analyses were then performed to evaluate the relevant influencing factors of clinical outcomes. Finally, R software was utilized to construct the nomogram. Results A total of 213 patients were defined as having a lower basal metabolic rate (LBMR). Univariate and multivariate analyses showed that gastric cancer patients with LBMR were more prone to postoperative complications and had poor long-term overall survival (OS). The established nomogram had good predictive power to assess the risk of OS in gastric cancer patients after radical gastrectomy (c-index was 0.764). Conclusions Overall, LBMR on admission is associated with the occurrence of postoperative complications in gastric cancer patients, and this population has a poorer long-term survival. Therefore, there should be more focus on the perioperative management of patients with this risk factor before surgery.

GDF15 ameliorates sepsis-induced lung injury via AMPK-mediated inhibition of glycolysis in alveolar macrophage

Growth differentiation factor 15 (GDF15) as a stress response cytokine is involved in the development and progression of several diseases associated with metabolic disorders. However, the regulatory role and the underlying mechanisms of GDF15 in sepsis remain poorly defined. Our study analyzed the levels of GDF15 and its correlations with the clinical prognosis of patients with sepsis. In vivo and in vitro models of sepsis were applied to elucidate the role and mechanisms of GDF15 in sepsis-associated lung injury. We observed strong correlations of plasma GDF15 levels with the levels of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and lactate as well as Sequential Organ Failure Assessment (SOFA) scores in patients with sepsis. In the mouse model of lipopolysaccharide-induced sepsis, recombinant GDF15 inhibited the proinflammatory responses and alleviated lung tissue injury. In addition, GDF15 decreased the levels of cytokines produced by alveolar macrophages (AMs). The anti-inflammatory effect of glycolysis inhibitor 2-DG on AMs during sepsis was mediated by GDF15 via inducing the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α) and the expression of activating transcription factor 4 (ATF4). Furthermore, we explored the mechanism underlying the beneficial effects of GDF15 and found that GDF15 inhibited glycolysis and mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) signaling via promoting AMPK phosphorylation. This study demonstrated that GDF15 inhibited glycolysis and NF-κB/MAPKs signaling via activating AMP-activated protein kinase (AMPK), thereby alleviating the inflammatory responses of AMs and sepsis-associated lung injury. Our findings provided new insights into novel therapeutic strategies for treating sepsis.

Stem Cell Markers in Neoplasms and their Relationship with Progression-free and Overall Survival in Patients with Recurrence.

Gliomas account for 30% of primary brain tumors in adults, and despite the scientific progress in the field, recurrence is prevalent. Glioma Stem Cells (GSCs) can generate tumor cells in vivo and in vitro and they are associated with treatment resistance, tumor progression, and recurrence. Furthermore, the expression of SOX transcription factors (SOX1, SOX2, SOX9) in these cells is responsible for maintaining an oncogenic genotype and is associated with an aggressive tumor phenotype. The relationship between SOX transcription factors and their prognostic role in recurrent gliomas has not been described in detail. Therefore, we set out to describe the relationship between SOX expression and Progression-free Survival (PFS) and Overall Survival (OS) in patients with recurrent gliomas. In this observational study, we have retrospectively analyzed 69 patients, of which 20 met the inclusion criteria. The clinical, radiological, and histopathological findings have been described, and survival analysis has been performed according to SOX expression for PFS and OS. We found SOX1, SOX2, and SOX9 to show a non-statistically significant trend with increasing histopathological grade, co-expressed with Ki67, a cell proliferation factor. There has been found an inversely proportional correlation between the degree of immunopositivity of SOX1 and OS. A higher SOX1 immunopositivity could predict a worse clinical prognosis. There has also been found an interaction between a pluripotent genotype (GSC) and cell proliferation.

Clinical characteristics and prognosis of patients with incidentally discovered chest wall sarcoma compared with those of symptomatic patients.

Sarcomas of the bone and soft tissues are detected after the onset of pain, detectable mass and related symptoms in the absence of a standardized screening examination. However, primary chest wall sarcomas can be incidentally detected upon chest X-ray or computed tomography. Previous studies of incidental primary chest wall sarcomas lack prognosis and disease-specific clinical data. This study aimed to investigate the prognoses of patients with incidental chest wall sarcomas and compare them with those of symptomatic patients. This study included 18 patients diagnosed with primary chest wall sarcoma between 2010 and 2023. Patient information such as age, sex, tumour diameter, tumour location, symptoms, treatment, time to treatment initiation, pathological diagnosis and outcome were retrospectively analysed. Among the 18 patients, the sarcomas were incidentally detected in five by chest X-ray and computed tomography in three and two patients, respectively. The pathological diagnoses of the patients were Ewing sarcoma, Chondrosarcoma grade 1, grade 2, periosteal osteosarcoma and malignant peripheral nerve sheath tumour. The patients had no symptoms at the first visit to our hospital, and no lesions in other organs were detected at the time of the initial examination. At the final follow-up, the patients remained disease-free after radical treatment. The tumour sizes of the five patients were significantly smaller than those of patients with symptoms (P=0.003). The incidental detection of chest wall sarcomas and consequent early detection and treatment of tumours improves patient prognosis relative to that of symptomatically diagnosed patients.

A study on pulmonary function in children with obstructive sleep apnea hypopnea syndrome.

To investigate the pulmonary function of children with obstructive sleep apnea syndrome. A total of 328 children aged 3 to 12 years old who were evaluated for a sleep disorder from January 2022 to June 2023 were selected as the observation group, classified into mild, moderate, and severe categories based on the apnea hypopnea index. The number of children with mild, moderate, and severe obstructive sleep apnea is 228, 62, and 28 respectively. Additionally, 126 healthy individuals aged 3 to 13 years old undergoing health examinations during the same period were selected as the control group. All subjects underwent sleep respiratory monitoring, pulmonary function tests, and impulse oscillometry. Comparative analysis was performed on pulmonary function indices (forced vital capacity, maximum ventilation, inspiratory capacity, total lung capacity, and inspiratory reserve volume), and respiratory impedance indices (resonant frequency, total respiratory impedance, viscous resistance at 5 Hz, 20 Hz, and 35 Hz). Pulmonary function indices were also compared among patients in the observation group with mild, moderate, and severe conditions. In the observation group, the FVC pre% of patients decreased by 10.5 ± 5.99 compared to the control group. The MVV of the control group decreased by 28.10 ± 2.22 compared to patients in the observation group. The IC of the control group decreased by 0.68 ± 0.44 compared to patients in the observation group. The TLC of the control group decreased by 1.354 ± 0.51 compared to patients in the observation group. The ERV of the control group decreased by 0.53 ± 0.30 compared to patients in the observation group. Additionally, the Fres, Zrs, R5, R20, and R35 of the observation group were higher than those of the control group by 10.73 ± 0.18, 1.78 ± 0.24, 0.11 ± 0.17, 0.86 ± 0.13, and 0.02 ± 0.21, respectively. In sum, the pulmonary function indices of the observation group were significantly lower than those of the control group, while the respiratory impedance indices were higher (P < 0.05). Within the observation group, the pulmonary function indices of severe patients were lower than those of moderate and mild patients, and moderate patients had lower pulmonary function indices than mild patients (P < 0.05). The pulmonary function of children with obstructive sleep apnea syndrome is impaired and varies in severity. There are significant differences in pulmonary function, underscoring the importance of monitoring pulmonary function in these children for clinical assessment and treatment prognosis.

Comprehensive Pan-Cancer Analysis of Connexin 43 as a Potential Biomarker and Therapeutic Target in Human Kidney Renal Clear Cell Carcinoma (KIRC).

Background and Objectives: Connexin 43 (Cx43) is involved in the transfer of small signaling molecules between neighboring cells, thereby exerting a major influence on the initiation and progression of tumorigenesis. However, there is a lack of systematic research on Cx43 expression and its predictive role in clinical diagnosis and prognosis in pan-cancer. Materials and Methods: Several biological databases were used to evaluate the expression levels of GJA1 (encoding Cx43) and its diagnostic and prognostic significance in pan-cancer. We targeted kidney renal clear cell carcinoma (KIRC) and investigated the relationship between GJA1 expression and different clinical features of KIRC patients. Then, we performed cell-based experiments to partially confirm our results and predicted several proteins that were functionally related to Cx43. Results: The expression of GJA1 has a high level of accuracy in predicting KIRC. High GJA1 expression was remarkably correlated with a favorable prognosis, and this expression was reduced in groups with poor clinical features in KIRC. Cell experiments confirmed the inhibitory effects of increased GJA1 expression on the migratory capacity of human renal cancer (RCC) cell lines, and protein-protein interaction (PPI) analysis predicted that CDH1 and CTNNB1 were closely related to Cx43. Conclusions: GJA1 could be a promising independent favorable prognostic factor for KIRC, and upregulation of GJA1 expression could inhibit the migratory capacity of renal cancer cells.

Antibody and siRNA Nanocarriers to Suppress Wnt Signaling, Tumor Growth, and Lung Metastasis in Triple‐Negative Breast Cancer

AbstractThe paucity of targeted therapies for triple‐negative breast cancer (TNBC) causes patients with this aggressive disease to suffer a poor clinical prognosis. A promising target for therapeutic intervention is the Wnt signaling pathway, which is activated in TNBC cells when extracellular Wnt ligands bind overexpressed Frizzled7 (FZD7) transmembrane receptors. This stabilizes intracellular β‐catenin proteins that in turn promote transcription of oncogenes that drive tumor growth and metastasis. To suppress Wnt signaling in TNBC cells, this work develops therapeutic nanoparticles (NPs) functionalized with FZD7 antibodies and β‐catenin small interfering RNAs (siRNAs). The antibodies enable TNBC cell specific binding and inhibit Wnt signaling by locking FZD7 receptors in a ligand unresponsive state, while the siRNAs suppress β‐catenin through RNA interference. Compared to NPs coated with antibodies or siRNAs individually, NPs coated with both agents more potently reduce the expression of several Wnt related genes in TNBC cells, leading to greater inhibition of cell proliferation, migration, and spheroid formation. In two murine models of metastatic TNBC, the dual antibody/siRNA nanocarriers outperformed controls in terms of inhibiting tumor growth, metastasis, and recurrence. These findings demonstrate suppressing Wnt signaling at both the receptor and mRNA levels via antibody/siRNA nanocarriers is a promising approach to combat TNBC.

USP31 Activates the Wnt/β-catenin Signaling Pathway and Promotes Gastric Cancer Cell Proliferation, Invasion and Migration.

Gastric cancer (GC) has a poor prognosis because it is highly aggressive, yet there are currently few effective therapies available. Although protein ubiquitination has been shown to play a complex role in the development of gastric cancer, to date, no efficient ubiquitinating enzymes have been identified as treatment targets for GC. The TCGA database was used for bioinformatic investigation of ubiquitin-specific protease 31 (USP31) expression in GC, and experimental techniques, including Western blotting, qRT-PCR, and immunohistochemistry, were used to confirm the findings. We also analyzed the relationship between USP31 expression and clinical prognosis in patients with GC. We further investigated the effects of USP31 on the proliferation, invasion, migration, and glycolysis of GC cells in vitro and in vivo by using colony formation, CCK-8 assays, Transwell chamber assays, cell scratch assays, and cell-derived xenograft. Furthermore, we examined the molecular processes by which USP31 influences the biological development of GC. Patients with high USP31 expression have a poor prognosis because USP31 is abundantly expressed in GC. Therefore, USP31 reduces the level of ubiquitination of the Wnt/β-catenin pathway by binding to β-catenin, thereby activating glycolysis, which ultimately promotes GC proliferation and aggressive metastasis. USP31 inhibits ubiquitination of β-catenin by binding to it, stimulates the Wnt/β-- catenin pathway, activates glycolysis, and accelerates the biology of GCs, which are all demonstrated in this work.

Changes in the clinical course and prognosis of ulcerative colitis in Chinese populations: a retrospective cohort study.

Data on the natural course of Chinese patients with ulcerative colitis (UC) was lacking. This study aimed to evaluate the natural history and prognosis of patients with UC in the past 15 years in China. This cohort study included patients with UC in a tertiary hospital in southern China from 2007 to 2021 (cohort I: 2007-2011, cohort II: 2012-2016, cohort III: 2017-2021). Patients' clinical characteristics and natural history were analyzed retrospectively. Of 1,139 included patients, 683 patients presented with proctitis or left-sided colitis at diagnosis and 38.5% of them (263/683) developed proximal disease extension. Fifty-eight percent of patients experienced relapse, chronic continuous and intermittent active course. Five patients (0.4%) developed colorectal tumors/dysplasia. The overall surgery rate was 8.6%, and the rates were 14.2%, 7.8%, and 8.0% in the 3 cohorts, respectively (P= 0.059). Average time from diagnosis to surgery decreased from cohorts I to III (144 months vs. 36 months, P< 0.001), so did the use of glucocorticoids (58.2% vs. 43.5%, P< 0.001) and immunosuppressants (14.1% vs. 13.4%, P= 0.016), and days of hospitalization (13 days vs. 9 days, P< 0.001). Biologics were used more frequently during the first year (0.8%, 2.1%, and 13.7% for cohorts I to III, respectively; P< 0.001). The rate of mucosal healing increased over time. In Chinese UC patients, one-third of patients experienced proximal disease extension. The rates of malignancy and mortality were low. More biologics were used, while use of immunosuppressants and glucocorticoids were reduced over time. Early biologics use seemed to promote mucosal healing, but the rate of colectomy has not dramatically decreased.

Constructing immune and prognostic features associated with ADCP in hepatocellular carcinoma and pan-cancer based on scRNA-seq and bulk RNA-seq.

Despite the significant therapeutic outcomes achieved in systemic treatments for liver hepatocellular carcinoma (LIHC), it is an objective reality that only a low proportion of patients exhibit an improved objective response rate (ORR) to current immunotherapies. Antibody-dependent cellular phagocytosis (ADCP) immunotherapy is considered the new engine for precision immunotherapy. Based on this, we aim to develop an ADCP-based LIHC risk stratification system and screen for relevant targets. Utilizing a combination of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data, we screened for ADCP modulating factors in LIHC and identified differentially expressed genes along with their involved functional pathways. A risk scoring model was established by identifying ADCP-related genes with prognostic value through LASSO Cox regression analysis. The risk scoring model was then subjected to evaluations of immune infiltration and immunotherapy relevance, with pan-cancer analysis and in vitro experimental studies conducted on key targets. Building on the research by Kamber RA etal., we identified GYPA, CLDN18, and IRX5 as potential key target genes regulating ADCP in LIHC. These genes demonstrated significant correlations with immune infiltration cells, such as M1-type macrophages, and the effectiveness of immunotherapy in LIHC, as well as a close association with clinical pathological staging and patient prognosis. Pan-cancer analysis revealed that CLDN18 was prognostically and immunologically relevant across multiple types of cancer. Validation through tissue and cell samples confirmed that GYPA and CLDN18 were upregulated in liver cancer tissues and cells. Furthermore, in vitro knockdown of CLDN18 inhibited the malignancy capabilities of liver cancer cells. We have identified an ADCP signature in LIHC comprising three genes. Analysis based on a risk scoring model derived from these three genes, coupled with subsequent experimental validation, confirmed the pivotal role of M1-type macrophages in ADCP within LIHC, establishing CLDN18 as a critical ADCP regulatory target in LIHC.