UNASSIGNED: Allogeneic hematopoietic cell transplantation (alloHCT) possessed direct cytotoxicity and graft-versus-multiple myeloma effect (GvMM). Growing trials have shown survival benefits of performing alloHCT in both newly diagnosed and relapsed MM.
UNASSIGNED: We aimed to provide a comprehensive analysis in the recent 10 years to verify the efficacy and survival outcome of alloHCT in MM patients. A total of 61 studies which provide data between 14/04/2013 and 14/04/2023 and a total of 15,294 data from MM patients who had undergone alloSCT were included in our study. The best response rates (CR, VGPR, PR) and survival outcomes (1-, 2-, 3-,5-, and 10-year OS, PFS, NRM) were assessed. We further conducted meta-analysis in the NDMM/frontline setting and RRMM/salvage setting independently.
UNASSIGNED: The pooled estimate CR, VGPR, and PR rates were 0.45, 0.21, and 0.24, respectively. The pooled estimates of 1-, 2-, 3-, 5-, and 10-year OS were 0.69, 0.57, 0.45, 0.45, and 0.36, respectively; the pooled estimates of 1-, 2-, 3-, 5-, and 10-year PFS were 0.47, 0.35, 0.24, 0.25, and 0.28, respectively; and the pooled estimates of 1-, 2-, 3-, 5-, and 10-year NRM were 0.16, 0.21, 0.16, 0.20, and 0.15, respectively. In the NDMM/upfront setting, the pooled estimate CR rate was 0.54, and those for 5-year OS, PFS, and NRM were 0.69, 0.40, and 0.11, respectively. In a relapsed setting, the pooled estimate CR rate was 0.31, and those for 5-year OS, PFS, and NRM were 0.24, 0.10, and 0.15, respectively.
UNASSIGNED: Our results showed constant OS, PFS, and NRM from the third year onwards till the 10th year, suggesting that alloSCT has sustained survival benefits. Good response rate and promising survival outcome were observed in the NDMM/ frontline setting.
UNASSIGNED: Although comparing with other treatments, alloSCT had a lower response rate and poorer short-term survival outcome, long-term follow-up could reveal survival benefits of alloSCT in MM patients.

UNASSIGNED: The causal relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OS) remains unclear. This study aims to investigate the causal relationship and explore the potential metabolic mechanism and its mediating role.
UNASSIGNED: We conducted a comprehensive study, gathering data on 490,089 T2DM patients from the genome-wide association study (GWAS) database and selecting OS data from FinnGen and MRC-IEU sources, including 212,778 and 463,010 patients, respectively, for causal analysis. Simultaneously, we explored the potential roles of three obesity traits and 30 metabolic and inflammation-related mediating variables in the causal relationship.
UNASSIGNED: There is a strong causal relationship between T2DM and OS. The data from our two different database sources appeared in the same direction, but after correcting for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR), the direction became the same. T2DM may increase the risk of OS [odds ratio (OR) > 1.5, p < 0.001]. Steiger\'s test results show that there is no reverse causality. No risk factors related to glycolipid metabolism, amino acid metabolism, and inflammation were found to mediate the causal relationship.
UNASSIGNED: This study\'s findings indicate a robust causal relationship between T2DM and OS, influenced by relevant factors such as BMI. Our results shed light on the pathogenesis of OS and underscore the importance for clinicians to treat metabolic disorders to prevent osteoporosis.

BACKGROUND: Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism.
METHODS: We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism.
RESULTS: In this study, we found that extremely low concentrations of GNE-987(2-10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development.
CONCLUSIONS: This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.

OBJECTIVE: Mucinous breast cancer (MBC) is a kind of breast cancer (BC), which is rare in clinic, mainly for women, because of the low incidence rate, so there is no unified standard treatment protocol. Elderly patients have a poor prognosis due to their combined comorbidities. This study aims to investigate the effect of surgery and chemoradiotherapy on the prognosis of elderly female MBC patients and construct nomograms for predicting the OS and CSS in elderly female MBC patients.
METHODS: Data for female MBC patients over 65 years are obtained from the Surveillance, Epidemiology and End Results (SEER) database, patients were divided into two groups: the training set and the validation set. External validation data of the prediction model were provided by Kunming Hospital of Traditional Chinese Medicine. We used Cox regression modeling, which was used to identify independent risk factors affecting patient prognosis. After avoiding confounding bias according to the multifactorial Cox regression model, we used these screened statistically significant results to construct column-line plots. The performance of the model was tested using the consistency index (c-index), the calibration curve, and the area under the operating characteristic curve of the receiver (AUC). Subsequently, we used decision curve analysis (DCA) to examine the potential clinical value of our nomograms.
RESULTS: A total of 8103 elderly MBC female patients were extracted from the database SEER and were assigned to the training and validation set, randomly. A total of 83 patients from Kunming Hospital of Traditional Chinese Medicine were used in the external verification set. After multifactorial Cox regression analysis, we found that age, race, T-stage, M-stage, surgical approach, radiotherapy, and tumor size were independent risk factors for OS in elderly MBC patients. Similarly, independent risk factors of CSS included age, marital status, N stage, M stage, surgical approach, chemotherapy, and tumor size. The C-index for the OS training, validation, and external verification set were 0.731 (95%CI 0.715-0.747), 0.738 (95%CI 0.724-0.752), and 0.809 (95%CI 0.731-0.8874). The C-index of the training set, the validation set, and external verification set for CSS were 0.786 (95%CI 0.747-0.825), 0.776 (95%CI 0.737-0.815), and 0.84 (95%CI0.754-0.926), respectively. The AUC, calibration curves and DCA also showed good accuracy.
CONCLUSIONS: In this study, we construct a new nomogram to predict the prognosis of elderly patients with MBC. The nomograms have undergone internal and external validation and have been confirmed to have good clinical applicability. At the same time, we found that for elderly female MBC patients, surgery and radiotherapy significantly benefit their survival, but chemotherapy is not conducive to patient survival.

Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma (n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients.

Acute leukemia is a hematological malignancy affecting different organ systems including the eye and orbit through direct infiltration of tissues or secondary to hematological abnormalities. Ophthalmological manifestations in acute leukemia are variable ranging from asymptomatic presentation to serious manifestations that can alter the disease course and treatment. The purpose of this study is to detect the incidence of different ophthalmological manifestations in newly diagnosed acute leukemia patients and to assess the relationship between ocular findings and hematological characteristics and the sequel of these neoplasms. A cross-sectional study with analytical components was conducted on 222 newly diagnosed acute myeloid and acute lymphoblastic leukemia patients who presented at Oncology Center Mansoura University (OCMU) between January 2022 and February 2023. All patients underwent a complete ophthalmic evaluation at Mansoura Ophthalmology Center (MOC). The mean age was 43.45 ± 17.35 years (range, 17-85), and M/F was 137 (61.7%)/85 (38.3%). One-hundred and forty-four (64.9%) had acute myeloid leukemia (AML), and 78 (35.1%) had acute lymphoblastic leukemia (ALL). Ophthalmic manifestations were detected in 96 patients (43.2%). Among them, 4 (1.8%) had poor visual acuity. Retinal hemorrhage (19.8%) and Roth spots (17.1%) were the most common ocular manifestations. Other ophthalmological manifestations observed were orbital involvement (3.2%), ocular motility issues (1.4%), subconjunctival hemorrhage (5.9%), conjunctival chemosis (0.9%),lid swelling (4.1%), lid ecchymosis (3.2%), lagophthalmos (0.5%), lid ptosis (1.8%), retinal venous congestion & tortuosity (4.1%), preretinal hemorrhage (3.2%), vitreous hemorrhage (3.2%), macular affection (2.3%), retinal infiltration (1.8%), exudative retinal detachment (ERD) (1.8%), cotton-wool spots (0.9%), retinal vein occlusion (0.5%), papilledema (2.8%), optic disc infiltration (1.8%), disc pallor (1.8%).AML patients were significantly associated with a higher frequency of ocular affection, retinal hemorrhages, and Roth spots (P 0.028, 0.003, and 0.046, respectively) compared to ALL patients. Retinal hemorrhage was statistically significantly associated with anemia (P 0.021). Ophthalmological manifestations of acute leukemia are heterogeneous; they can be detected at initial presentations or relapse. Some manifestations are asymptomatic, others can affect visual acuity or even alter the disease course. Cooperation between ophthalmologists and haemato-oncologists is crucial for recognizing ocular involvement and disease management.

BACKGROUND: Doublet platin-chemotherapy was the old standard treatment for different histology types of advanced and metastatic lung cancer (LC) and is still an option for patients who are not eligible for immune checkpoint inhibitors. However, in low- and middle-income countries, chemotherapy, either in monotherapy or in combination with platinum, is still the only accessible option in public institutions. The efficacy of different platin-based chemotherapy in patients with LC who are treatment-naïve is unknown.
METHODS: In this retrospective study, we selected patients with advanced and metastatic (IIIB-IVB) non-squamous non-small cell LC (NSCLC), squamous NSCLC, and lung neuroendocrine tumours (small cell LC (SCLC), large cell neuroendocrine, and atypical carcinoid) aged beyond 18 years who received first-line chemotherapy (docetaxel, gemcitabine, etoposide, paclitaxel, pemetrexed, and vinorelbine) combined with platinum between January 1, 2013, and December 31, 2022. Within the population with non-squamous NSCLC, squamous NSCLC, and neuroendocrine tumours, progression-free survival (PFS) and overall survival (OS) were the primary assessed endpoints. Hematologic safety was the secondary endpoint.
RESULTS: Overall, 611 patients were included. In the group of patients with non-squamous NSCLC (n = 390), there was no statistical difference between subgroups of patients who received first-line platin-chemotherapy. The median PFS was 182 (95 % confidence interval [CI], 167-208) days (hazard ratio for progression: NR [Not Reached]; p = 0.37), and the median OS was 446 (95 % CI, 405-559) days (hazard ratio for death: 1.31; 95 % CI, 0.94 - 1.82; p = 0.1). In the group of patients with squamous NSCLC (n = 149), we note the absence of statistical significance between subgroups of patients who received platin-based chemotherapy. The median PFS was 195 (95 % CI, 142-238; hazard ratio for progression: 1.21, 95 % CI, 0.29-5.02; p = 0.27), while the median OS was 428 (95 % CI, 324-940) days (hazard ratio for death: 1.76; 95 % CI, 0.93 to 3.3; p = 0.32). The absence of significance has been noticed in the neuroendocrine subgroup of patients who received first etoposide-platinum, vinorelbine-platinum, or paclitaxel-platinum (n = 72). The median PFS was 216 (95 % CI, 193-277) days; hazard ratio for progression: 1.74, 95 % CI, 0.41-7.27; p = 0.69, while the median OS was 273 (95 % CI, 241-459) days (hazard ratio for death: 2.95; 95 % CI, 0.4-21.7; p = 0.51). Grade 3-4 neutropenia grade was the predominant adverse event associated with chemotherapy in almost 11 % of patients.
CONCLUSIONS: Moving forward, treatment strategies must be refined for patients, with an emphasis on increasing the number of patients who can benefit from emergent approaches in order to guarantee a wider, deeper, and longer-lasting outcome.

UNASSIGNED: Intestinal-type gastric adenocarcinoma, representing 95 % of gastric malignancies, originates from the malignant transformation of gastric gland cells. Despite its prevalence, existing methods for prognosis evaluation of this cancer subtype are inadequate. This study aims to enhance patient-specific prognosis evaluation by analyzing the clinicopathological characteristics and prognostic risk factors of intestinal-type gastric adenocarcinoma patients using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI).
UNASSIGNED: We extracted clinical data for patients diagnosed with intestinal-type gastric adenocarcinoma between 2010 and 2015 from the SEER database, selecting 257 cases based on predefined inclusion and exclusion criteria. Independent risk factors for overall survival (OS) and cancer-specific survival (CSS) were identified using a Cox regression model. A nomogram model for predicting OS or CSS was developed from the Cox risk regression analysis and validated through the consistency index (C-index), ROC curve, and calibration curve.
UNASSIGNED: Age, primary tumor resection, chemotherapy, lymph node metastasis, and tumor size were identified as independent prognostic factors for OS and CSS (P < 0.05). The nomogram model, constructed from these indicators, demonstrated superior predictive consistency for OS and CSS compared to the AJCC-TNM staging system. ROC curve analysis confirmed the model\'s higher accuracy, and calibration curve analysis indicated good agreement between the nomogram\'s predictions and actual observed outcomes.
UNASSIGNED: The nomogram model derived from SEER database analyses accurately predicts OS and CSS for patients with intestinal-type gastric adenocarcinoma. This model promises to facilitate more tailored treatments in clinical practice.

OBJECTIVE: The aim of this study was to quantitatively compare the efficacy and safety of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors for ER+/HER2- metastatic breast cancer.
METHODS: A parametric survival function was used to analyze the time course of overall survival (OS) and progression-free survival (PFS). The objective response rate (ORR) and the incidence of any grade and grade 3-4 adverse events were summarized using the random-effects model of a single-arm meta-analysis.
RESULTS: This study included 44 arms from 48 publications, with a total sample size of 7881 patients. Our study revealed that CDK4/6 inhibitors had a median OS of 40.7 months, a median PFS of 14.8 months, and an ORR of 40%, whereas PI3K/AKT/mTOR inhibitors had a median OS of 29.8 months, a median PFS of 8.3 months, and an ORR of 20%. Additionally, this study also found that the proportion of patients with visceral metastases and specific endocrine therapy used in combination significantly impact OS and PFS. In terms of adverse events, CDK4/6 inhibitors exhibited a relatively high incidence of hematological adverse events.
CONCLUSIONS: Our study provides solid quantitative evidence for the first-line recommendation of CDK4/6 inhibitors combined with endocrine therapy for ER+/HER2- metastatic breast cancer in clinical guidelines.

OBJECTIVE: This study aimed to evaluate the clinicopathological and prognostic significance of preoperative serum creatine kinase (CK) levels in colorectal cancer.
METHODS: This study analyzed 1169 patients with colorectal cancer at stages 0 (n = 35), I (n = 301), II (n = 456), III (n = 339), and IV (n = 38). The CK cut-off value was 52 U/L to predict recurrence based on receiver operative characteristics curve. Clinicopathological factors were compared between the low (< 52 U/L) and high CK groups (≥ 52 U/L). The multivariate analysis evaluated relapse-free survival (RFS) and overall survival (OS) following CK status.
RESULTS: The female sex, elderly age (≥ 75), deep tumor (pT4), and carcinoembryonic antigen (+) were independently associated with low CK status. The recurrent rate was significantly higher in the low CK group than in the high CK group (19.1% vs. 11.7%, p < 0.001). Elderly age, pT4, pN (+), preoperative carbohydrate antigen (CA) 19-9 (+), and low CK status were independent risk factors for RFS. Elderly age, pT4, pN (+), preoperative CA19-9 (+), and low CK status were independent risk factors for OS.
CONCLUSIONS: Preoperative low CK status was associated with deep tumors and was a poor prognostic factor in patients with colorectal cancer.