Progression of disease within 24 months (POD24) in multiple myeloma implicates poor prognosis and limitations of current prediction models for POD24.

Multiple myeloma (MM) is a common hematological malignancy, and its prognostic factors have been extensively studied. Progression of disease within 24 months (POD24) suggests a poor prognosis in many malignancies, but is rarely mentioned in MM. This study aimed to investigate the prognostic value of POD24 in MM and risk factors of POD24, and to evaluate the predictive value of existing MM prognostic models for POD24. The research retrospectively analyzed the clinical data of MM patients and found that the occurrence of POD24 is an independent prognostic factor affecting overall survival in MM, while non-transplantion and genetic abnormality are independent risk factors for the occurrence of POD24. The existing prognostic models are not effective in predicting POD24. Therefore, it's still necessary to explore a prognostic model that can predict POD24 more accurately.

Comparison of Epstein-Barr virus copy number in white blood cells of chronic lymphocytic leukemia patients with laboratory prognostic biomarker.

BACKGROUND AND OBJECTIVE: The DNA load of EBV may play a part in CLL pathogenesis and prognosis. The objective of this cross-sectional study was to examine the prognostic value of EBV viral load in CLL patients in comparison with other common laboratory prognostic factors. MATERIALS AND METHODS: Whole blood and sera from forty untreated CLL patients were collected. Next, DNA was extracted from total white blood cells (WBC), and TaqMan real-time PCR was performed to determine the EBV-DNA load by amplifying a specific fragment in the BNRF1 gene. In addition, parameters such as complete blood counts (CBC) and lactate dehydrogenase (LDH) were determined using an automated clinical laboratory analyzer. RESULTS: Twenty-one patients (52.5%) were positive for EBV by real-time PCR analysis (ranged 20 to 30000 copies/µL). The difference in LDH mean levels between EBV positive and negative patients was marginally significant (P = 0.05). Furthermore, platelet (PLT) count (P = 0.03) and CD5+/CD19+ count (P = 0.04), between EBV positive and negative subgroups, were substantially different. In addition, individuals with a severe form of illness, as defined by an increase in LDH, a decrease in PLT, and an 11q deletion, had considerably higher EBV-DNA copy numbers (the ranges of viral loads were 9966.66 ± 20033 in the severe form vs. 137.13 ± 245.41 in the mild form). CONCLUSION: The EBV-DNA load could be used as a prognostic factor in the initial examination of CLL patients to better characterize the disease outcome and prognosis.

Preoperative Serum Glycan Levels Reflect Progression of Patients With Hepatocellular Carcinoma.

BACKGROUND: Abnormal glycosylation is associated with tumors. The clinical value of serum glycans in assessing progression of hepatocellular carcinoma (HCC) patients remains a challenge. METHODS: A study dynamically comparing levels of fifteen lectin-specific glycans between preoperative and postoperative serum of 65 HCC patients was conducted via lectin biochip technology. Multivariable logistic regression analysis was used to address associations between serum glycan levels and clinicopathological characteristics. Kaplan-Meier analysis was used to evaluate the impacts of serum glycan levels on overall survival (OS) and progression-free survival (PFS) of the HCC patients. RESULTS: HCC patients presented significantly higher levels of the lectin-specific glycans in preoperative serum than disease-free individuals (p < 0.001 - p = 0.029), except ConA. The glycans in preoperative sera were significantly related to tumor size, pTNM, metastasis, BCLC stage, portal hypertension (PHT), and platelet count (PLT), respectively (p < 0.05). Multivariate logistic analyses indicated that tumor size and pTNM independently impact on glycan-specific lectins either LTL, UEA-I, VVL, NPL, WGA, PNA, MAL-I, SNA, or PHA-L (p = 0.003 - p = 0.044); BCLC stage and PLT were independent factors influencing the serum glycans recognizable DSA (p = 0.024) and SNA (p = 0.050), respectively. Surgical excision of tumor mass significantly reduced glycan levels in sera. Tumor differentiation, albumin, and ABO type significantly revealed independent influence on glycan-specific lectins, such as RCA-I (p = 0.024), VVL (p = 0.024), and Con A (p = 0.026) in the postoperative serum. HCC patients with high levels of VVL-binding glycans significantly benefited from a longer OS time (p = 0.016, HR: 0.460, 95% CI: 0.237-0.892) and a better PFS time (p = 0.004; HR: 0.435, 95% CI: 0.237-0.799), respectively. CONCLUSION: Serum glycans could reflect surgical outcomes in at-risk patients and become valuable biomarkers in evaluating the progression of HCC patients.

UBE2Q1 as a novel cancer biomarker for lung adenocarcinoma.

PURPOSE: Ubiquitin-conjugating enzymes (E2s) participate in various tumor-promoting processes. UBE2Q1 is a member of the E2 family. This research aimed to detect the expression level of UBE2Q1 in human lung adenocarcinoma and to study its malignant biological function. METHODS: Western blot, qRT-PCR and immunohistochemistry was used to measure the expression of UBE2Q1 in human lung adenocarcinoma tissues. The association between UBE2Q1 expression and clinic-pathological variables in 99 lung adenocarcinoma samples was analyzed by immunohistochemistry. In vitro experiment, establishing UBE2Q1 knockdown pattern, the markers of apoptosis, cell cycle and epithelial-mesenchymal transition (EMT) were analyzed by Western blot. CCK8, colony formation, Transwell and invasion assay analyzed the effect of UBE2Q1 knockdown on the proliferation, metastasis and invasion of lung cancer cells. RESULTS: UBE2Q1 was overexpressed in lung adenocarcinoma, and the expression level of UBE2Q1 was related with TNM stage, tumor size, and lymph node metastasis. The high level of UBE2Q1 expression was also associated with poor survival and was an independent risk factor. In vitro, It was also confirmed that steady downregulation of UBE2Q1 could promote apoptosis, induce G2/M cell cycle arrest and regulate EMT. UBE2Q1 silencing dramatically reduce lung tumor cells proliferation, migration and invasion capacities. CONCLUSIONS: UBE2Q1 may serve as a prognostic biomarker and a new therapeutic target of lung adenocarcinoma.

The clinical outcomes and prognostic factors of dedifferentiated central chondrosarcoma in extremities.

OBJECTIVE: This study was to analyze the clinical outcomes and prognostic factors of dedifferentiated central chondrosarcomas (DCCS) in extremities. METHODS: A retrospective study was conducted on 49 patients (27 males, 22 females) who underwent surgical treatment between January 2001 and March 2023 in our institution. All patients were diagnosed with dedifferentiated central chondrosarcomas by needle biopsy or postoperative histopathological examination. The general characters, treatment and clinical outcomes were recorded in the follow-up and all surgical-related complications that occurred were recorded in this study. Overall, these data were used to analyse the prognostic factors of DCCS. RESULTS: 49 patients were included in this retrospective study and there were no patients lost in the follow-up period. The median diagnosis age of all patients was 57 years old (ranging from 17 to 87) and the median follow-up time was 34 months (range, 1-289). The average tumor size was 9.6 ± 2.4 cm (3.0-15.5). Median overall survival (OS) and progression-free survival (PFS) were 34 and 23 months, respectively. The 1-year, 2-year, 5-year, and 10-year OS were 87.8% (95% CI 77.6%-98.0%), 71.4% (35/49), 28.6% (14/49) and 18.4% (9/49). And the 1-year, 2-year, 5-year, and 10-year PFS were 75.5% (95% CI 63.6%-87.4%), 49.0% (35/49), 26.5% (14/49) and 16.3% (9/49). Multiple variate analyses indicated metastasis, pathological fracture, Enneking staging and surgical margin were independent prognostic factors in extremity dedifferentiated central chondrosarcomas. CONCLUSIONS: Dedifferentiated central chondrosarcomas in extremities still had a grave prognosis. Metastasis, pathological fracture, Enneking staging, and surgical margin were independent risk factors for prognosis. EVIDENCE LEVEL: IV Therapic.

High circulating activin A plasma levels are associated with tumour stage and poor survival in treatment-naive lung squamous cell cancer patients.

OBJECTIVES: Lung squamous cell carcinoma (LUSC) is associated with a poor prognosis and a lack of specific treatment options. The dysregulation of activin A (ActA) has been reported in various malignancies. Herein, we investigated the diagnostic and prognostic significance of ActA in LUSC. MATERIALS AND METHODS: ActA concentrations were measured using ELISA in plasma samples of 128 LUSC patients (stage I-IV) and 73 controls, and correlated those values with clinicopathological parameters and survival. RESULTS: ActA plasma levels were significantly higher in therapy-naive LUSC patients compared to controls (444.1 ± 310.9 pg/mL vs 338.9 ± 145.5 pg/mL, p = 0.010). ActA levels significantly correlated with advanced stage as well as with T and N factors. High circulating ActA levels were significantly increased in metastatic disease patients compared to M0 disease. Further, patients with ActA levels above a computationally established optimal cut-off value of 443.0 pg/mL had a significantly worse median overall (OS, 17.63 vs 64.77 months, HR 0.391, 95 % CI 0.200-0.762, p < 0.001) and median disease-/progression-free survival (DFS/PFS; 11.57 vs 30.20 months, HR 0.502, 95 % CI 0.248-1.019, p = 0.020). Multivariate analysis revealed that high ActA levels were an independent prognostic factor for shorter OS (p = 0.001) and DFS/PFS (p = 0.018). A newly developed score combining CRP and ActA levels was also an independent prognostic factor for OS and DFS/PFS. CONCLUSION: Measurement of circulating ActA levels may help identify advanced-stage LUSC patients, and this value could serve as a prognostic parameter in LUSC. Thus, ActA may be a novel blood-based biomarker for identifying LUSC patients with distant metastasis.

Nomograms predicting benefit after immunotherapy in oral bifidobacteria supplementation ICC patients: a retrospective study.

PURPOSE: The objective of this study was to develop nomograms for predicting outcomes following immunotherapy in patients diagnosed with intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHODS: A retrospective analysis was conducted on data from 75 ICC patients who received immunotherapy at Jinling Hospital and Drum Hospital. The discriminative power, accuracy, and clinical applicability of the nomograms were assessed using the concordance index (C-index), calibration curve, and decision curve analysis (DCA). The predictive performance of the nomograms for overall survival (OS) and progression-free survival (PFS) was evaluated using the area under the receiver operating characteristic (ROC) curve. Kaplan-Meier curves were also generated for validation purposes. RESULTS: Multivariable analysis identified independent prognostic factors for OS, including CA19-9 levels, portal vein tumor thrombus (PVTT) grade, bifidobacteria administration, and surgery. The C-index of the nomogram for OS prediction was 0.722 (95% confidence interval [CI]: 0.661-0.783). Independent prognostic factors for PFS included CA19-9 levels, albumin, and bilirubin, with a C-index of 0.678 (95% CI: 0.612-0.743) for the nomogram predicting PFS. Calibration curves demonstrated strong concordance between predicted and observed outcomes, while DCA and Kaplan-Meier curves further supported the clinical utility of the nomogram. CONCLUSION: The nomogram developed in this study demonstrated favorable performance in predicting the prognosis of ICC patients undergoing immunotherapy. Additionally, our findings, for the first time, identified probiotics as a potential prognostic marker for immunotherapy. This prognostic model has the potential to enhance patient selection for immunotherapy and improve clinical decision-making.

Prognostic factors and risk-stratification model of recurrent or metastatic head and neck squamous cell carcinoma treated with cetuximab containing regimen.

BACKGROUND: In recent years, the addition of cetuximab to chemotherapy has improved treatment outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this study, we present the real-world survival data of R/M HNSCC patients who received cetuximab-containing regimens from thirteen medical centers in Taiwan, as well as a three-level risk stratification model for this patient population. METHODS: This study enrolled R/M HNSCC patients from thirteen medical centers in Taiwan who received cetuximab-containing regimens from January 1, 2017 to June 6, 2022. The cases were divided into a training cohort and a validation cohort based on the start of treatment. Overall survival (OS) was evaluated in both cohorts and exploratory analysis was performed to identify associated adverse clinical and laboratory factors. The results of the exploratory analysis were used to construct a three-level risk stratification prediction model for OS. RESULTS: A total of 1434 patients with R/M HNSCC were enrolled in this study and received cetuximab-containing regimens. The overall population had a median OS of 8.57 months (95% CI: 8.07 - 9.08). Multivariate analysis of the training cohort identified poor ECOG performance status, heavy alcohol consumption, and prior adjuvant CCRT or lack of prior RT as adverse prognostic factors. Comparison of laboratory data between patients with OS≦6 and OS > 6 also revealed unfavorable factors, including increased white blood cell count, decreased hemoglobin level, increased platelet count, increased absolute neutrophil count, decreased absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio. Using forward prediction, a three-level risk stratification prediction model was constructed using the variables of ECOG performance status, alcohol consumption, skin metastasis, modality of radiation therapy, hemoglobin level, and neutrophil-to-lymphocyte ratio. The median OS in the low-risk, intermediate-risk, and high-risk groups were 12.02 months (95% CI 10.44-13.61), 7.5 months (95% CI 7.33-8.17), and 4.01 months (95% CI 3.94-4.08), respectively, with a log-rank test p-value < 0.001. CONCLUSION: This study presents a three-level risk stratification model with strong prediction ability for OS in R/M HNSCC patients who received cetuximab-containing regimens. The results are based on real-world data and may provide valuable information for clinicians in treatment planning and future drug development.

Prognostic factors of visual outcome in central serous chorioretinopathy treated with subthreshold micropulse laser therapy.

Analyze the prognostic factors of visual outcome in central serous choriretinopathy (CSC) treated with subthreshold micropulse laser (SML) therapy through the most fundamental medical history and clinical examinations. It was a retrospective clinical study. We collected the most fundamental medical history and clinical examinations of CSC patients who received SML treatment, including visual acuity (VA) and spectral-domain optical coherence tomography (SD-OCT) of macular. Eyes were divided into two groups according the change of central macular thickness (CMT) before and one month after SML: CMT improvement and CMT deterioration group; divided into three groups according the change of VA: VA improvement, VA stability and VA decline group. Seventy-eight patients (eighty-three eyes) were enrolled. The baseline CMT was 339.83 ± 115.72 µm, and the baseline VA was 0.43 ± 0.36. One month after SML, CMT was 281.13 ± 121.48 µm, had a significant statistical improvement (p = 0.000); and VA was 0.46 + 0.42, had no significant statistical difference compared to baseline VA (p = 0.114). CMT of sixty-three eyes (75.90%) declined, and twenty eyes (24.10%) increased; VA of thirty-one eyes (37.35%) improved, fourteen eyes (16.87%) remained unchanged, and thirty-eight eyes (45.78%) declined. CMT and VA of twenty-seven eyes (32.53%) were both improved, and eleven eyes (13.25%) were both deteriorated. VA one month after SML was statistically correlated with age (p = 0.000), baseline VA (p = 0.000), and baseline CMT (P = 0.002). CMT and VA both improved one month after SML, and the improvement of CMT was more significant than VA. Elder age and poorer baseline vision indicated poorer VA one month after SML, while higher baseline CMT indicated better VA one month after SML.

Value of the lung immune prognostic index in patients with advanced small cell lung cancer treated with programmed death-ligand 1 and programmed death-1 inhibitors in the Chinese alpine region.

Purpose: To assess the potential added value of the lung immune prognostic index (LIPI) in patients with small cell lung cancer (SCLC), treated with programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) inhibitors, who lived in the Chinese alpine region. Methods: 120 SCLC patients treated with PD-L1/PD-1 inhibitors were divided into three LIPI groups, from July 2018 to April 2021. Cox regression models were used to evaluate the prognostic effect of three LIPI groups on overall survival (OS) and progression-free survival (PFS). Logistic regression analysis was conducted to explore the association between immune-related adverse events (irAEs) and the pretreatment of neutrophil-to-lymphocyte ratio (dNLR), lactate dehydrogenase (LDH), and LIPI. Results: The median OS was 4.5, 6.3, and 10.0 months (p=0.001) and the median PFS was 2.5, 4.3, and 5.3 months (p=0.049) for Poor, Intermediate, and Good LIPI, respectively. The disease control rate (DCR) was also higher in the Good LIPI group (p=0.003). Moreover, multivariate analysis confirmed that worse LIPI was correlated with shorter OS and PFS. dNLR was associated with the onset of irAEs, not LIPI. Conclusion: The LIPI might be a promising predictive and prognostic biomarker in SCLC patients treated with PD-L1/PD-1 inhibitors in the Chinese Alpine region.

Clinical Evaluation of Acute Exacerbation of Interstitial Lung Disease in a Single Tertiary Center: Perspectives before and after the Coronavirus Disease 2019 Pandemic.

Background/Objectives: Acute exacerbation (AE) of interstitial lung disease (ILD) is a major challenge. This study aimed to retrospectively investigate occurrences of AEs in patients with ILDs, including idiopathic pulmonary fibrosis (IPF), non-IPF (iNSIP: idiopathic nonspecific interstitial pneumonia), and connective tissue disease (CTD)-associated ILDs (CTD-ILDs), at a single tertiary center before and after the coronavirus disease 2019 (COVID-19) pandemic. The study aimed to clarify the seasonal and regional trends of AEs of ILDs, assess the roles of viral and bacterial infections, and identify key prognostic factors for patient outcomes. Methods: We conducted a retrospective review of hospitalized adult patients with AEs of ILDs from January 2019 to February 2024. Results: A total of 93 patients were enrolled: IPF (n = 42), iNSIP (n = 37), and CTD-ILDs (n = 14). The median age was 80 years (interquartile range: 74.0-86.0 years), with males comprising 64.5% (n = 60). AEs of ILDs predominantly occurred in winter and were particularly notable after summer 2023, coinciding with the lifting of COVID-19-related travel restrictions in Japan. Patient referrals from different areas (Northern Tama, East and/or Southern Tama, and other Tokyo metropolitan areas) were evenly distributed throughout the study period. Viral infections were detected in only two patients (SARS-CoV-2), and bacterial infections included methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. The Cox regression analysis identified serum lactate dehydrogenase levels ≥350 IU/L and tachypnea (respiratory rate ≥ 30 breaths per min) on admission as prognostic factors for mortality, with a hazard ratio [HR] of 2.783 (95% confidence interval [CI]: 1.480-5.235, p = 0.001) and an HR of 3.332 (95% CI: 1.710-6.492, p < 0.001), respectively. Conclusions: AEs of ILDs predominantly occur in winter, and viral and bacterial infections are infrequently detected. Elevated serum LDH levels and tachypnea are crucial prognostic markers for mortality. This study highlights the seasonal trend in the AE of ILD and emphasizes the importance of specific prognostic indicators in clinical practice.

Prognostic value of immune-inflammatory and nutrition indicators in non-metastatic nasopharyngeal carcinoma with negative plasma Epstein-Barr virus DNA.

Background: Plasma Epstein-Barr virus (EBV) DNA has been identified as a significant prognostic marker for nasopharyngeal carcinoma (NPC), yet there is limited research on the prognosis of NPC patients with negative EBV DNA. Objectives: We explore the prognostic value of comprehensive immune-inflammatory and nutritional indicators to offer personalized treatment recommendations and prognosis predictions for non-metastatic NPC patients with negative EBV DNA. Design: This was a retrospective study. Methods: This study retrospectively analyzed 257 non-metastatic NPC patients with negative EBV DNA between January 2015 and December 2019. The Kaplan-Meier survival curves evaluated survival endpoints, and group discrepancies were assessed with log-rank tests. Principal component analysis (PCA) reduced data dimensionality. Univariate and multivariate Cox regression analyses identified significant prognostic variables. Risk stratification was performed based on recursive partitioning analysis (RPA). A robust prognostic model was constructed by nomogram and evaluated by calibration curves, decision curves, and the time-dependent area under the curve analysis. Results: PCA was employed to compute the immune-inflammation index (III) and nutrition index (NI). Multivariate Cox regression analysis revealed lactate dehydrogenase, III, and NI as significant prognostic variables for overall survival (OS). Utilizing RPA, we stratified the risk into three categories: low-risk group (low III + high NI), middle-risk group (low III + low NI), and high-risk group (high III). Both the middle- (p = 0.025) and high-risk groups (p < 0.001) exhibited poorer OS compared with the low-risk group. The nomogram model exhibited superior predictive accuracy compared to tumor lymph node metastasis stage alone (C-index: 0.774 vs 0.679). Conclusion: Our study validated the prognostic significance of III and NI in non-metastatic NPC patients with negative EBV DNA. Additionally, a clinical risk stratification was constructed to offer valuable insights into the individualized treatment of these patients.

Biomarkers of inflammation and nutrition can effectively predict the prognosis of EBV DNA-negative non-metastatic nasopharyngeal carcinoma Why was the study done? Plasma Epstein-Barr virus (EBV) DNA has shown efficacy in predicting survival and disease progression in individuals with nasopharyngeal carcinoma (NPC). However, a subset of patients exhibit negative EBV DNA levels. Currently, there is limited research available on the prognostic implications for this particular patient population. What did the researchers do? The researchers gathered clinical data from Fujian Cancer Hospital between 2015 and 2019 in order to investigate the potential of immune-inflammatory and nutritional markers in predicting both survival rates and disease progression among patients diagnosed with EBV DNA-negative, non-metastatic NPC. Additionally, the study aimed to assess the feasibility of utilizing these markers to offer personalized treatment recommendations for this specific patient population. What did the researchers find? A total of 257 non-metastatic NPC patients with negative EBV DNA were included in the study for clinical data collection. The findings suggest that a lower immune-inflammation index and a higher nutrition index were correlated with extended overall survival (OS) in this patient population. Furthermore, the study indicates that the survival advantage of abstaining from induction chemotherapy (IC) may be more pronounced in this particular cohort. What do the findings mean? This study has identified immune-inflammatory and nutritional markers as predictive of survival in NPC patients with EBV DNA-negative and raised thinking about reducing treatment intensity and improving the quality of life in this population patients in the future.

The Prognostic Implications of Synchronous Cancers in Breast Cancer Patients.

OBJECTIVE: This study aims to examine the prognostic value of synchronous cancer diagnosis following an initial diagnosis of breast cancer, with a focus on site-specific survival rates and the correlation between primary breast cancer and secondary cancers. METHODS: We conducted a retrospective analysis of patients treated at Saint Nicholas Hospital in Pitesti, Romania, from January 2016 to January 2024. The inclusion criteria were a confirmed diagnosis of primary breast cancer and a secondary synchronous cancer diagnosed within two months. Data collection included demographic, clinical, and pathological characteristics, as well as treatment details and follow-up outcomes. Statistical analyses were performed using SPSS software version 26.0 (IBM Corp., Armonk, New York, USA), employing Kaplan-Meier survival curves, Cox regression models, and other relevant statistical tests. RESULTS: Out of 73 initially identified patients, 49 met the inclusion criteria. The mean age was 59.6 years, with most patients being postmenopausal. Synchronous cancers were primarily contralateral breast cancer (44.9%) and female genital organ cancer (12.24%). Patients with synchronous bilateral breast cancer had significantly better overall survival (33 months) compared to those with other synchronous cancers (23.5 months). Multivariate analysis indicated that synchronous non-breast cancers were associated with a higher risk of death (hazard ratio (HR)=1.6, 95% CI: 1.22-2.10, p=0.003). CONCLUSION: Synchronous cancer diagnosis following an initial breast cancer diagnosis significantly impacts prognosis, with synchronous bilateral breast cancer associated with better survival outcomes compared to other synchronous cancers. These findings underscore the importance of vigilant screening and personalized treatment strategies for patients with synchronous malignancies.

Long-term prognostic characteristics of patients with clinical stage IA part-solid lung adenocarcinoma: a conditional survival analysis.

OBJECTIVES: Despite excellent 5-year survival, there are limited data on the long-term prognostic characteristics of clinical stage IA part-solid lung adenocarcinoma. The objective was to elucidate the dynamics of prognostic characteristics through conditional survival analysis. METHODS: Consecutive patients who underwent complete resection for clinical stage IA part-solid lung adenocarcinoma between 2011 and 2015 were retrospectively reviewed. Conditional survival is defined as the probability of surviving further y years, conditional on the patient has already survived x years. The conditional recurrence-free survival (CRFS) and conditional overall survival (COS) were analysed to evaluate prognosis over time, with conditional Cox regression analysis performed to identify time-dependent prognostic factors. RESULTS: A total of 1539 patients were included with a median follow-up duration of 98.4 months, and 80 (5.2%) patients experienced recurrence. Among them, 20 (1.3%) recurrence cases occurred after 5 years of follow-up with 100% intrathoracic recurrence. The 5-year CRFS increased from 95.8% to 97.4%, while the 5-year COS maintained stable. Multivariable Cox analysis revealed that histologic subtype was always an independent prognostic factor for CRFS even after 5 years of follow-up, while the independent prognostic value of consolidation-to-tumour ratio, visceral pleural invasion and lymph node metastasis was observed only within 5 years. Besides, age, pathologic size and lymph node metastasis maintained independent predictive value for COS during long-term follow-up, while consolidation-to-tumour ratio was predictive for COS only within 5 years of follow-up. CONCLUSIONS: The independent prognostic factors for clinical stage IA part-solid lung adenocarcinoma changed over time, along with gradually increasing 5-year CRFS and stable 5-year COS.

The Dilemma for Early-Stage Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma: To Treat or Not to Treat?

BACKGROUND: Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALToma) is typically treated with radiotherapy. Some studies suggested a "wait and watch" approach due to the adverse effects of radiotherapy. However, the benefits of observation for localized conjunctival MALToma remain unclear. Therefore, we aimed to explore the clinical course of early-stage conjunctival MALToma, distinguish heterogeneity between T1 and T2 patients, and identify prognostic factors. METHODS: This retrospective study involved patients with stage T1-T2 conjunctival MALToma and lasted >6 months. Clinical characteristics were compared between T1 and T2 subjects. Prognostic factors were examined with Cox regression. RESULTS: The research comprised 32 subjects with early-stage conjunctival MALToma, of whom 25% underwent observation. No individuals expired regardless of choosing observation or radiotherapy. The T1 patients were younger (p = 0.002) and more inclined towards observation only (p = 0.035) than the T2 subjects. Despite more of the T1 patients undergoing watchful waiting than the T2 subjects, the T1 patients seemed to have longer systemic relapse-free survival than the T2 subjects (17 vs. 13 years, p = 0.343). CD43 may imply poor prognosis (p = 0.049). CONCLUSIONS: Careful observation may be suggested for early-stage conjunctival MALToma. While more of the T1 individuals were younger and chose observation than the T2 patients, survival seemed longer in the T1 subjects without significance. CD43 may indicate shorter survival in early-stage cases.

RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients.

BACKGROUND: The molecular system of receptor activator of nuclear factor kappa-ß (RANK) and its ligand (RANKL) plays a role in a variety of physiological and pathological processes. These encompass the regulation of bone metabolism, mammary gland development, immune function, as well as their involvement and tumorigenesis. Nevertheless, limited knowledge exists regarding their function within the tumor microenvironment. METHODS AND RESULTS: We explored the significance of RANK expression in cancer-associated fibroblasts (CAFs) as a prognostic biomarker in early breast cancer patients (BCPs) by immunohistochemistry. Results reveal a significant correlation between high RANK expression in CAFs and an increased risk of metastasis (p= 0.006), shorter metastasis-free survival (MFS) [p= 0.007, OR (95%CI) = 2.290 (1.259-4.156)], and lower overall survival (OS) [p= 0.004, OR (95%CI) = 2.469 (1.343-4.541)]. Upon analyzing the phenotype of CD34(-) CAFs isolated from primary tumors in BCPs, we observed co-expression of RANK with CD105 marker by immunofluorescence and flow cytometry, characteristic of mesenchymal stem/stromal cells (MSCs), suggesting the possible cellular origin. Also RANKL-RANK system increase the OCT-4, SOX-2 and DKK-1 (dickkopf 1) gene expression in CD34(-) CAFs by RT-PCR. Moreover, this system plays a crucial role in the migration of these CD34(-) CAFs. CONCLUSIONS: These results support the clinical relevance of RANK in CAFs and propose its potential as a future therapeutic target in the treatment of early BCPs.

Do corticosteroids affect immunotherapy efficacy in malignancy? - A systematic review.

BACKGROUND: Early studies indicated that corticosteroids may limit the survival benefit from immunotherapy. We conducted this systematic review to evaluate the effect corticosteroids have on immunotherapy in patients with malignancy, when adjusted for potentially confounding effects of corticosteroids given for palliative indications. METHODS: Three electronic databases (PubMed, Embase and Medline) were searched on 1 February 2023. Studies that measured response or survival to immunotherapy in people receiving corticosteroids for non-cancer indications compared to either no corticosteroids or corticosteroids for cancer-related indications were included. Studies exclusively evaluating the effect of corticosteroids administered for immune-related adverse events (irAE) were excluded to avoid immortal time bias. Pooled odds and hazard ratios with 95% confidence intervals (CI) were calculated using a random effects model. Study heterogeneity was assessed using the I2 statistic, and publication bias was evaluated by funnel plot and Egger's regression model. RESULTS: Eight thousand four hundred and twenty-six titles were identified on our search. Eight studies met our inclusion criteria for meta-analysis. Administration of corticosteroids does not have a statistically significant effect on survival and response to immunotherapy when administered for non-cancer-related indications, with a pooled odds ratio for overall response rate 1.01 (95% CI 0.64-1.60); pooled hazard ratio (HR) for progression free survival 0.87 (95% CI 0.68-1.12); and pooled HR for overall survival 0.79 (95% CI 0.59-1.05). CONCLUSION: This systematic review indicates that administration of corticosteroids does not affect response to immunotherapy nor survival outcomes, when removing confounding palliative corticosteroid indications. These results are limited by the retrospective nature of the studies included, small sample sizes, lack of information about corticosteroid dosing and the inclusion of irAE in two of the studies which could bias the results.

Preoperative fibrinogen level predicts the risk and prognosis of patients with native valve infective endocarditis undergoing valve surgery.

Aim: The aim of this study was to assess the clinical significance and prognostic value of the preoperative fibrinogen (FBG) level in patients with native valve infective endocarditis (NVIE) who underwent valve surgery. Methods: This retrospective study included a total of 163 consecutive patients who were diagnosed with NVIE and underwent valve surgery from January 2019 to January 2022 in our hospital. The primary endpoint was all-cause mortality. Results: All-cause mortality was observed in 9.2% of the patients (n = 15). Body mass index (BMI) was lower in the survival group (p = 0.025), whereas FBG (p = 0.008) and platelet count (p = 0.044) were significantly greater in the survival group than in the death group. Multivariate Cox proportional hazards analysis revealed that FBG (HR, 0.55; 95% CI, [0.32-0.94]; p = 0.029) was an independent prognostic factor for all-cause mortality. Furthermore, Kaplan‒Meier survival curve analysis revealed that patients with low FBG levels (<3.28 g/L) had a significantly greater mortality rate (p = 0.034) than did those with high FBG levels (>3.99 g/L). In the trend analysis, the FBG tertiles were significantly related to all-cause mortality in all three adjusted models, and the p values for trend were 0.017, 0.016, and 0.028, respectively. Conclusion: Preoperative FBG may serve as a prognostic factor for all-cause mortality, and an FBG concentration less than 3.28 g/L was associated with a greater risk of all-cause mortality in NVIE patients undergoing valve surgery.

The efficacy of neoadjuvant immunotherapy and lymphocyte subset predictors in locally advanced esophageal squamous cell carcinoma: A retrospective study.

BACKGROUND: Despite the recognized therapeutic potential of programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in advanced esophageal squamous cell carcinoma (ESCC), their role in neoadjuvant therapy and reliable efficacy biomarkers remain elusive. MATERIALS AND METHODS: We retrospectively analyzed locally advanced ESCC patients who underwent surgery following a 2-cycle platinum and paclitaxel-based treatment, with or without PD-1 inhibitors (January 2020-March 2023). We assessed peripheral blood indexes and tertiary lymphoid structures (TLS) density to evaluate their impact on pathological response and prognosis, leading to a clinical prediction model for treatment efficacy and survival. RESULTS: Of the 157 patients recruited, 106 received immunochemotherapy (ICT) and 51 received chemotherapy (CT) alone. The ICT group demonstrated a superior pathological response rate (PRR) (47.2% vs. 29.4%, p = 0.034) with comparable adverse events and postoperative complications. The ICT group also showed a median disease-free survival (DFS) of 39.8 months, unattained by the CT group. The 1-year DFS and overall survival (OS) rates were 73% and 91% for the ICT group, and 68% and 81% for the CT group, respectively. We found higher baseline activated T cells, lower baseline Treg cells, and a decreased posttreatment total lymphocyte and CD4+/CD8+ ratio predicted an enhanced PRR. Reduced posttreatment CD4+/CD8+ ratio and increased NK cells were associated with prolonged survival, while higher TLS density indicated poorer prognosis. Among ICT group, a lower posttreatment CD4+/CD8+ ratio indicated longer DFS and reduced posttreatment B cells indicated longer OS. A nomogram integrating these predictors was developed to forecast treatment efficacy and survival. CONCLUSION: The combination of PD-1 inhibitors and chemotherapy appears promising for locally advanced ESCC. Evaluating the differentiation status and dynamic changes of peripheral blood immune cells may provide valuable predictive insights into treatment efficacy and prognosis.