Poor Prognostic Factor In Patients Research Articles

Thrombocytopenia With High C-reactive Protein in Myeloma Patients Treated With Proteasome Inhibitor and/or Immunomodulatory Drugs.

Background/Aim: Thrombocytopenia is a poor prognostic factor in patients with myeloma; however, the factors associated with thrombocytopenia have not been extensively discussed. This study aimed to investigate the clinical significance of thrombocytopenia, defined as 130×103/μl or less, in patients with newly diagnosed multiple myeloma (NDMM) treated with proteasome inhibitors and/or immunomodulatory drugs. This is a retrospective review of medical records of myeloma patients treated between 2000 and 2021. A total of 241 patients were included in this study, with a median age of 72 years. Overall survival (OS) and time to next treatment (TTNT) were assessed using Kaplan-Meier analysis and Cox regression analysis. Prognostic factors were evaluated by univariate and multivariate analyses. The incidence of thrombocytopenia was 17.8%. In the median follow-up period of 46.6 months, OS and TTNT in the thrombocytopenia group were significantly shorter than those in the non-thrombocytopenia group using multivariate analysis (p<0.001 and p<0.001). C-reactive protein (CRP) level was not associated with thrombocytopenia, and high CRP predicted short OS and TTNT independently from thrombocytopenia. When the low (neither thrombocytopenia nor high CRP), intermediate (either thrombocytopenia or high CRP), and high (thrombocytopenia and high CRP) risk groups were defined, the OS and TTNT among these groups showed significant differences; the hazard ratios for survival in the high and intermediate risk groups were 7.022 and 2.598, and for TTNT, they were 4.216 and 1.887, respectively, compared to the low-risk group. Thrombocytopenia was associated with the activity of NDMM and predicted prognosis in NDMM. When combined with high CRP levels, thrombocytopenia serves as a new indicator of poor prognosis in these patients.

Association between estimated glomerular filtration rate and prognosis in patients with cardiovascular disease with and without sarcopenia

Abstract Background/Introduction A low estimated glomerular filtration rate (eGFR) has been identified as a poor prognostic factor in patients with cardiovascular diseases (CVD). Since serum creatinine, which defines eGFR, is a metabolite of skeletal muscle, low skeletal muscle mass can result in reduced creatinine production and potentially overestimate renal function. This raises concerns about the reliability of eGFR as a prognostic indicator in patients with both CVD and sarcopenia. The impact of this relationship, however, remains uncertain. Purpose This study aimed to explore the association between eGFR and prognosis in patients with CVD, both with and without sarcopenia. Methods We included 2,444 CVD patients (mean age 69.0 ± 13.7 years) who had assessments of eGFR and sarcopenia at discharge. Sarcopenia was diagnosed according to the 2019 Asian Sarcopenia Working Group Diagnostic Criteria. Patients were categorized into sarcopenia and non-sarcopenia groups, each further divided into high eGFR (eGFR ≥60 mL/min/1.73 m²) and low eGFR (eGFR &amp;lt;60 mL/min/1.73 m²) subgroups. Kaplan-Meier curves, log-rank tests, and multivariate Cox regression analyses were employed to compare prognoses between these groups, adjusting for age, sex, BMI, left ventricular ejection fraction (LVEF), history of myocardial infarction (MI), acute coronary syndrome (ACS), heart failure (HF), hypertension (HT), dyslipidaemia (DL), diabetes mellitus (DM), and smoking history. The primary endpoint was a composite of all-cause mortality and rehospitalization. Results Median follow-up was 1.11 (interquartile range [IQR], 0.43–2.32) years for the non-sarcopenia group and 0.94 (IQR, 0.30–2.15) years for the sarcopenia group. Event rates were 24.2% in the non-sarcopenia group and 30.8% in the sarcopenia group. Both Kaplan-Meier and log-rank tests indicated that a low eGFR, regardless of sarcopenia status, was associated with a higher incidence of composite events (p &amp;lt; 0.001). Multivariate Cox regression analysis revealed a significant association between low eGFR and increased risk of composite events in both the non-sarcopenia [hazard ratio (HR): 1.55, 95% confidence interval (CI): 1.44–1.67; p &amp;lt; 0.001] and sarcopenia groups [HR: 1.36, 95% CI: 1.25–1.48; p &amp;lt; 0.001]. Conclusion Low eGFR is associated with poor prognosis in patients with CVD, irrespective of sarcopenia status.

Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinoma

AbstractAimThe relationship between sarcopenia, tumor‐infiltrating lymphocytes (TILs), and long‐term survival in patients with hepatocellular carcinoma (HCC) has not been investigated. We aimed to evaluate the prognostic relevance of sarcopenia and TILs in patients with HCC.MethodsWe included 351 patients with HCC following liver resection. Sarcopenia was defined based on the skeletal muscle index using computed tomography. Tumor‐infiltrating CD4+ and CD8+ T cells, perforin, and granzyme B were examined in liver resection specimens.ResultsSarcopenia patients had a significantly lower lymphocyte count (p = 0.003), prognostic nutritional index (p = 0.017), and CD4+ and CD8+ T cell counts (p = 0.008 and p = 0.006, respectively). The overall survival (OS) and recurrence‐free survival (RFS) rates of sarcopenia patients were significantly lower than non‐sarcopenia patients (both p &lt; 0.001). Multivariate analysis revealed that sarcopenia and low CD8 levels were strong independent poor prognostic factors for OS and RFS (both p &lt; 0.001). Regardless of sarcopenia, patients with high CD8 levels had significantly better OS and RFS rates and increased expression of perforin and granzyme B. Particularly, sarcopenia patients with high CD8 levels had much better OS and RFS than those with low CD8 levels and were even comparable to non‐sarcopenia patients with high CD8 levels.ConclusionsSarcopenia and low CD8 levels are strong independent poor prognostic factors in patients with HCC. Furthermore, sarcopenia patients with high CD8 levels had favorable survival and activated local immunity, suggesting that tumor‐infiltrating CD8+ T cells may play a functionally important role in sarcopenia patients.

MYO6 contributes to tumor progression and enzalutamide resistance in castration-resistant prostate cancer by activating the focal adhesion signaling pathway

BackgroundEnzalutamide (Enz) resistance is a poor prognostic factor for patients with castration-resistant prostate cancer (CRPC), which often involves aberrant expression of the androgen receptor (AR). Myosin VI (MYO6), one member of the myosin family, plays an important role in regulating cell survival and is highly expressed in prostate cancer (PCa). However, whether MYO6 is involved in Enz resistance in CRPC and its mechanism remain unclear.MethodsMultiple open-access databases were utilized to examine the relationship between MYO6 expression and PCa progression, and to screen differentially expressed genes (DEGs) and potential signaling pathways associated with the MYO6-regulated Enz resistance. Both in vitro and in vivo tumorigenesis assays were employed to examine the impact of MYO6 on the growth and Enz resistance of PCa cells. Human PCa tissues and related clinical biochemical data were utilized to identify the role of MYO6 in promoting PCa progression and Enz resistance. The molecular mechanisms underlying the regulation of gene expression, PCa progression, and Enz resistance in CRPC by MYO6 were investigated.ResultsMYO6 expression increases in patients with PCa and is positively correlated with AR expression in PCa cell lines and tissues. Overexpression of AR increases MYO6 expression to promote PCa cell proliferation, migration and invasion, and to inhibit PCa cell apoptosis; whereas knockdown of MYO6 expression reverses these outcomes and enhances Enz function in suppressing the proliferation of the Enz- sensitive and resistant PCa cells both in vitro and in vivo. Mechanistically, AR binds directly to the promoter region (residues − 503 to − 283 base pairs) of MYO6 gene and promotes its transcription. Furthermore, MYO6 activates focal adhesion kinase (FAK) phosphorylation at tyrosine-397 through integrin beta 8 (ITGB8) modulation to promote PCa progression and Enz resistance. Notably, inhibition of FAK activity by Y15, an inhibitor of FAK, can resensitize CRPC cells to Enz treatment in cell lines and mouse xenograft models.ConclusionsMYO6 has pro-tumor and Enz-resistant effects in CRPC, suggesting that targeting MYO6 may be beneficial for ENZ-resistant CRPC therapy through the AR/MYO6/FAK signaling pathway.

Next-Generation Integrated Sequencing Identifies Poor Prognostic Factors in Patients with MYD88-Mutated Chronic Lymphocytic Leukemia in Taiwan.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western countries and is very rare in Asia. Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 215 patients with CLL were analyzed by using next-generation sequencing to investigate the ethnic differences in genetic abnormalities. Whole-genome sequencing and whole-exome sequencing analyses on 30 cases showed that 9 genes, including IGLL5, MYD88, TCHH, DSCAM, AXDND1, BICRA, KMT2D, MYT1L, and RBM43, were more frequently mutated in our Taiwanese cohort compared with those of the Western cohorts. IGLL5, MYD88, and KMT2D genes were further analyzed by targeted sequencing in another 185 CLL patients, unraveling frequencies of 29.3%, 20.9%, and 15.0%, respectively. The most frequent positional mutation of MYD88 was V217F (26/45, 57.8%), followed by L265P (9/45, 20.0%). MYD88 mutations were significantly associated with IGLL5 mutations (p = 0.0004), mutated IGHV (p < 0.0001) and 13q deletion (p = 0.0164). CLL patients with co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations were associated with a significantly inferior survival compared to those with MYD88 mutation alone (not reached vs. 131.8 months, p = 0.007). In multivariate analysis, MYD88 mutation without KMT2D or IGLL5 mutations was an independently favorable predictor. IGLL5, MYD88, and KMT2D mutations were enriched in Taiwanese CLL, and co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations was associated with a poorer prognosis.

Leakage sign based on contrast-enhanced CT is a predictive marker for hematoma expansion and poor prognosis in primary brainstem hemorrhage

BackgroundAlthough hematoma expansion is a poor prognostic factor in patients with intracerebral hemorrhage (ICH), its effect on primary brainstem hemorrhage (PBSH) remains unclear. Since we previously observed the “leakage sign” (LS) on computed tomography (CT) to be a significant predictor for hematoma expansion, we herein investigated the effect of LS in PBSH. MethodsBetween January 2013 and August 2023, 515 patients with ICH were admitted to our institute. Thirty-six patients with PBSHs met the inclusion criteria, who were then divided into LS-positive (LS+) and LS-negative (LS-) groups based on the presence of LS. We evaluated hematoma expansion and prognosis at discharge. ResultsPatients in the LS+ group had larger baseline hematoma volume and lower Glasgow Coma Scale scores on admission and significantly poor prognosis at discharge. Subgroup analysis revealed that LS was frequently observed within 100 min after the onset of symptoms in patients with a hematoma size of >10 mm3 on CT; additionally, patients in the LS+ group more frequently experienced hematoma expansion and had poor prognosis at discharge. ConclusionLS is a significant predictive marker for disease severity at admission, hematoma expansion, and poor prognosis at discharge

Utility of atezolizumab plus bevacizumab, carboplatin, and paclitaxel combination for the treatment of advanced non-squamous non-small cell lung cancer patients with malignant pleural effusion.

Malignant pleural effusion (MPE) remains a negative prognostic factor in non-small cell lung cancer (NSCLC), even after the emergence of immune checkpoint inhibitors. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Bevacizumab, a humanized monoclonal antibody against VEGF, is a key agent for patients who develop MPE. However, it is unclear whether MPE is a poor prognostic factor in patients with advanced non-squamous NSCLC receiving treatment with the atezolizumab plus bevacizumab, carboplatin, and paclitaxel (ABCP) regimen. Moreover, the effect of ABCP on MPE control is unknown. This study aimed to elucidate the efficacy and safety of ABCP for non-squamous NSCLC patients with MPE. We retrospectively analyzed consecutive patients with advanced non-squamous NSCLC who received treatment with ABCP (January 2019-September 2023). Patients were divided into two groups (non-MPE and MPE), and treatment outcomes were compared. In the MPE group, treatment efficacy for MPE control and toxicity were evaluated. Of the 46 patients enrolled, 17 and 29 were included in the non-MPE and MPE groups, respectively. The objective response and disease control rates were not significantly different between the non-MPE and MPE groups (76.5% vs. 51.7%, P=0.13; 88.2% vs. 82.8%, P>0.99; respectively). Similarly, the median progression-free survival and median overall survival were not significantly different (9.9 vs. 10.1 months, P=0.87; 16.0 vs. 19.9 months, P=0.87, respectively). In the MPE group, 25 patients (86.2%) achieved MPE control lasting >8 weeks from the initiation of treatment with ABCP; the median progression-free survival without an unequivocal increase in MPE was 15.0 months. The incidence rates of grade ≥3 non-immune- and immune-related adverse events were 83% and 17%, respectively. There was no treatment-related death. The ABCP regimen may be a promising treatment option for non-squamous NSCLC patients with MPE.

Prognostic impact of DTA mutation and co-occurring mutations in patients with myelodysplastic syndrome.

To evaluate the frequency and prognostic significance of DTA (DNMT3A、TET2、ASXL1) gene mutation and co-occurring mutations in patients with myelodysplastic syndrome (MDS). The clinical data of 102 newly diagnosed MDS patients who accepted Next Generation Sequencing (NGS) was retrospectively analyzed. According to whether the patients had DTA gene mutation, the patients were divided into DTA mutated (DTA-mut) group and wild type (DTA-wt) group, and the relationship between gene mutation and clinical characteristics and prognosis was analyzed. Among the 102 MDS patients, 96% (98/102) presented with mutation, while the mean number of mutations was 3.04 mutations/patient. DTA-mut was detected in 56.9% (58/102) patients. The most frequent co-mutated genes in DTA-mut group were SF3B1 (25.8%), RUNX1 (24.1%), U2AF1 (18.9%), SRSF2, EZH2, SETBP1 (17.2%), STAG2 (15.5%), IDH2 (12.1%) and BCOR, CBL (10.3%). The two groups showed no significant differences in ages, blood parameters, bone marrow blasts, WHO 2022 classification, IPSS-R risk category and rate of conversion to leukemia. Compared with the DTA-wt group, the mutation frequency of RUNX1 was higher (P = 0.02), while mutation frequency of TP53 was lower (P = 0.001) and the mutation frequency of ≥ 3 co-mutated genes was higher in DTA-mut group (P = 0.00). Survival analysis showed that the overall survivals (OS) of DTA-mut patients was significantly inferior to that of DTA-wt patients (P = 0.0332). According to IPSS-R classification, a statistically significant difference in OS was only observed in higher risk (IPSS-R > 3.5) group (P = 0.0058). In the context of DTA mutation, the OS of patients with RUNX1 mutation was shorter than that of patients without RUNX1 mutation significantly (P = 0.0074). The OS of patients with SF3B1 mutation was longer than that of patients without SF3B1 mutation, but there was no statistical difference (P = 0.0827). DTA mutations were not independent prognostic factors when DTA and co-mutated genes with frequency > 10% were considered in Cox regression model (P = 0.329). However, multivariate analysis confirmed an independently adverse prognosis of RUNX1 co-mutation (P = 0.042, HR = 2.426, 95% CI:1.031-5.711) in DTA-mut cohort. Moreover, our multivariable analysis suggests that SRSF2-mutwas an independent poor prognostic factor for all MDS patients (P = 0.047), but lost significance (P = 0.103) for DTA-mut patients. DTA mutations are frequently observed in patients with MDS, often accompanied by genes involved in RNA splicing and transcription factors like SF3B1 and RUNX1. DTA and concomitant mutations affect prognosis in MDS patients and RUNX1 was identified as an independent poor prognostic factor in patients with DTA mutations.

Number of positive lymph nodes and lymph node ratio predict recurrence and survival in hypopharyngeal cancer based on SEER database and validation of real-world data.

This study investigated the impacts of the number of positive lymph nodes (NPLN) and lymph node ratio (LN ratio) for patients with hypopharyngeal squamous cell carcinoma (HPSCC) based on SEER database, which were validated in the real-world data of China. A total of 520 patients from SEER database were analyzed. Then 195 patients with pathologically stage III or IV HPSCC in our center were retrospectively studied. In the SEER database, NPLN ≥ 3 was found in 36.9% of patients. Multivariate analysis revealed that LN ratio ≥ 0.138 was significant with poorer overall survival (OS) (hazard ratio [HR] = 1.525, p = 0.001) and cancer-specific survival (CSS) (HR = 1.697, p < 0.001), so was the NPLN ≥ 3 (HR = 1.388, p = 0.013; HR = 1.479, p = 0.008). Patients with NPLN ≥ 3 were found in 103 (52.8%) in our center. Multivariate analysis confirmed a significant association regarding OS (p = 0.005) or CSS (p = 0.003) between patients with LN ratio ≥ 0.138 or not. In addition, disease recurrence rate differed significantly between the patients with NPLN ≥ 3 (27.2%) and NPLN < 3 (14.1%, p = 0.026). Moreover, postoperative chemoradiotherapy (CCRT) was significantly associated with better prognosis in patients with NPLN ≥ 3. In the SEER database, NPLN ≥ 3 and LN ratio ≥ 0.138 were independent poor prognostic factors for patients with HPSCC. Whereas identifying worldwide cut-off values for LN ratio is difficult and surgeon-dependent. In our cohort, adjuvant CCRT was beneficial for OS in patients with NPLN ≥ 3.

Risk factors for and prognostic impact of lateral pelvic lymph node metastasis in patients with rectal neuroendocrine tumors: a single-center retrospective analysis of 214 cases with radical resection.

Lateral pelvic lymph node (LPLN) metastasis of rectal neuroendocrine tumors (NETs) is rare, with unknown oncological features. We investigated the oncological impact of LPLN metastasis in patients with rectal NETs. This study included 214 patients with rectal NETs who underwent curative surgery. We evaluated their clinicopathological characteristics and short- and long-term outcomes. LPLN dissection was performed in 15 patients with LPLN swelling ≥ 7mm (preoperative imaging); 12 patients had LPLN metastases, 6 of whom had LPLN metastases without mesorectal lymph node metastases (skip metastasis). The short-term outcomes were similar between the groups with and without LPLN dissection. The median follow-up period was 59.4months, and patients with LPLN metastasis showed significantly shorter disease-free and overall survival rates than those without metastasis. Among 199 patients who did not undergo LPLN dissection, only 1 had LPLN recurrence. In a univariate analysis, tumor depth, tumor grade, and LPLN metastasis were associated with the overall survival. In the multivariate analysis, only LPLN metastasis was an independent predictor of the overall survival. LPLN metastasis is a poor prognostic factor for patients with rectal NETs. LPLN enlargement can be considered an indication for dissection, owing to its high rate of metastasis and associated poor prognosis.

Impact of interstitial lung disease gender-age-physiology index in surgically treated lung cancer.

The postoperative prognosis of patients with interstitial lung disease (ILD) and lung cancer is poor. Recently, the ILD-gender-age-physiology (GAP) index was identified as a clinical prognostic factor for patients with ILD. This study investigated the ILD-GAP index and oncological factors regarding postoperative outcomes. We retrospectively reviewed 87 lung cancer patients with comorbid ILD who underwent curative resection at our institution between April 2005 and December 2019. Short-term postoperative outcomes and overall survival (OS) based on the ILD-GAP index were examined. OS rates after surgery were calculated using the Kaplan-Meier method, and group differences were analyzed using the Log-Rank test. Univariate and multivariate analyses for OS were performed using the Cox regression model. Multivariate analyses revealed ILD-GAP index ≥ 4 [Hazard ratio, 3.349; 95% confidence interval 1.375-8.155; P = 0.008] as a factor associated with OS. In the ILD-GAP index ≥ 4 group, no deaths occurred from primary lung cancer, with respiratory-related deaths being the most common, and exacerbation of ILD was more frequent (P = 0.007). Regarding perioperative results, a significant difference was observed in 90-day mortality (2.7% vs. 23.0% [P = 0.022]), and more patients required home oxygen therapy (14.9% vs. 69.2% [P < 0.001]) in the ILD-GAP index ≥ 4 group. An ILD-GAP index ≥ 4 indicated a poor prognostic factor for patients with surgically treated lung cancer. Careful consideration of surgical indications is essential for patients with an ILD-GAP index ≥ 4.

The indication of palliative whole-brain radiotherapy for patients with brain metastases: a simple prognostic scoring system in the era of stereotactic radiosurgery

BackgroundStereotactic irradiation has become the mainstay treatment for brain metastases (BM), and whole-brain radiotherapy (WBRT) is often used for symptom palliation. However, the survival time of patients with BM undergoing palliative WBRT (pWBRT) is limited, making it difficult to select patients who should receive treatment.MethodsWe collected patient data from 2016 to 2022 at the Shizuoka Cancer Center and retrospectively analyzed the factors related to survival time. Overall survival (OS) was defined as the survival time after WBRT.ResultsA total of 301 patients (median age, 66 years) who underwent pWBRT were included. The primary cancers were lung, breast, gastrointestinal tract, and other cancers in 203 (67%), 38 (13%), 33 (11%), and 27 (9%) patients, respectively. Median OS of all patients was 4.1 months. In the multivariate analysis, male sex (hazard ratio [HR]:1.4), Karnofsky Performance Status (KPS) ≤ 60 (HR:1.7), presence of extracranial metastasis (ECM) (HR:1.6), neutrophil-lymphocyte ratio (NLR) ≥ 5 (HR:1.6), and lactate dehydrogenase (LDH) ≥ upper limit of normal (ULN) (HR:1.3) were significantly associated with shorter OS (all P < 0.05). To predict the OS, we created a prognostic scoring system (PSS). We gave one point to each independent prognostic factor. Median OS for patients with scores of 0–2, 3, and 4–5 were 9.0, 3.5 and 1.7 months, respectively (P < 0.001).ConclusionsMale sex, KPS ≤ 60, presence of ECM, NLR ≥ 5, and LDH ≥ ULN were poor prognostic factors for patients with BM undergoing pWBRT. By PSS combining these factors, it may be possible to select patients who should undergo pWBRT.

Endoscopic ultrasound with tissue acquisition of lymph nodes in patients with potentially resectable intrahepatic cholangiocarcinoma.

Background and study aims Lymph node (LN) involvement is a poor prognostic factor for patients with intrahepatic cholangiocarcinoma (iCCA). The aim of this study was to evaluate the yield and impact on clinical decision making of endoscopic ultrasound with tissue acquisition (EUS-TA) of LNs in patients with potentially resectable iCCA. Patients and methods In this multicenter cohort study, patients with potentially resectable iCCA and preoperative EUS between 2010 and 2020 were retrospectively included. The impact of EUS-TA was defined as the percentage of patients who did not undergo surgical exploration due to pathologically confirmed positive LNs found with EUS-TA. Results A total of 56 patients underwent EUS, with 91% of patients to target suspicious LNs on imaging. EUS-TA of LNs confirmed malignancy in 21 LNs among 19 patients (34%). In 17 patients (30%), surgical exploration was withheld due to nodal involvement. Finally, 24 patients (43%) underwent surgical exploration among whom positive regional LNs were identified in six patients (25%). Conclusions In patients with potentially resectable iCCA and suspicious LNs on cross-sectional imaging, EUS-TA confirmed LN involvement in 30% of patients. Surgical exploration was withheld mostly because of extraregional LN involvement and regional LN involvement in patients with high surgical risk.

Evaluation of preoperative visceral fat area / psoas muscle area ratio and prognosis in patients with colorectal cancer

AbstractBackgroundRecent research has focused on the prognostic relevance of preoperative sarcopenia and sarcopenic obesity in various cancers. In this study we investigated the relationship between visceral fat area (VFA), psoas muscle area (PMA), and the prognosis of patients undergoing colorectal cancer surgery.MethodsPatients with stage III colorectal cancer who underwent surgery between July 2013 and April 2020 were included. The analysis was performed on 151 patients who met the criteria. The VFA and PMA were measured at the level of the third lumbar vertebra on computed tomography (CT) scans, and the ratio of VFA to PMA (V/P ratio) was determined.ResultsPatients with high V/P ratios were significantly older (p = 0.0213), had a higher body mass index (BMI) (p &lt; 0.0001), a higher percentage of sarcopenic obesity (p &lt; 0.0001), and more diabetes complications (p &lt; 0.0001). Prognostic analysis showed that the overall survival (OS) (p = 0.0154) and relapse‐free survival (RFS) (p = 0.0378) were significantly worse in patients with a high V/P ratio. Multivariate analysis revealed that a high V/P ratio was an independent poor prognostic factor for OS. Subgroup analysis was then performed in patients with BMI &lt; 25 kg/m2. OS (p = 0.0259) and RFS (p = 0.0275) were significantly worse in the high V/P ratio group. A high V/P ratio was an independent poor prognostic factor in the multivariate analysis.ConclusionIn colorectal cancer, the preoperative V/P ratio is an independent factor for poor prognosis. Preoperative evaluation of the V/P ratio may identify a wide range of high‐risk patients because it is an independent poor prognostic factor in patients without obesity.

Prognostic value of weight loss in hospitalized patients with heart failure.

Weight loss is a poor prognostic factor in patients with chronic heart failure (HF). However, whether the same is true for hospitalized patients with HF is unknown, even though hospitalization is the first opportunity for many patients to be diagnosed with HF. This study aimed to investigate the prognostic value of weight loss in patients hospitalized for HF. This was a post-hoc analysis of the FRAGILE-HF study, a prospective multi-center, observational study including 1,332 hospitalized older (≥65 years) patients with HF. The primary outcome was all-cause death within two years of discharge. Self-reported body weight data one year prior to hospital admission were available for 1,106 patients (83.0%) and were compared with their weight after decongestion therapy. The median weight change was -6.9% [-2.4 - -11.9] and 86.8% of the overall cohort experienced some weight loss. Whereas patients with weight loss ≥ 5%, which is a well-validated cut-off in chronic HF, had comparable mortality to those with less weight loss (p = 0.96 by log-rank test), patients with weight loss > 12%, the lowest quartile value, had higher mortality than those with less weight loss (p = 0.024 for all-cause mortality, p = 0.028 for non-cardiovascular mortality, and p = 0.28 for cardiovascular mortality, respectively). In a Cox proportional hazard model, > 12% weight loss was associated with high mortality after adjusting for known prognostic factors and history of malignancy (adjusted hazard ratio: 1.485 [1.070-2.062], p=0.018). Weight loss derived from patient-reported body weight one year before hospitalization was significantly associated with increased mortality after discharge, mainly due to non-cardiovascular etiology, in elderly patients hospitalized for HF.

Multicenter study on clinical outcomes and poor prognostic factors in patients with Klebsiella pneumoniae bacteremia receiving cefoperazone/sulbactam treatment

BackgroundInfections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied.ObjectivesThis study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates.MethodsThis multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients’ clinical outcomes and characteristics were collected and analyzed.ResultsIn total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07–1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31–14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50–12.27; p = 0.006) were independently associated with unfavorable outcomes.ConclusionPatients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes.

Late-Term Outcomes of Surgical Treatment of Infective Endocarditis.

Background: This study aims to evaluate the long-term outcomes of surgical interventions in patients with infective endocarditis (IE) who underwent surgical treatment and to determine the treatment approach for new patients. Patients and Methods: We retrospectively examined the long-term results of patients who underwent surgical treatment for IE between 2007 and 2017. The evaluation included late-term outcomes of IE surgery, surgical procedures, complications, the postoperative period, and clinical findings. Results: The study included 20 patients (12 male, 8 female) with a mean age of 45.1 ± 17.25. The most common cardiac risk factors for endocarditis development were the presence of prosthetic valves and heart valve disease. In addition, non-cardiac risk factors included chronic renal failure, systemic lupus erythematosus, and pemphigus vulgaris. Preoperative and postoperative laboratory findings were compared with in terms of morbidity and mortality, revealing no significant differences. The most prevalent preoperative laboratory findings were anemia (100%), elevated CRP (100%), and leukocytosis (50%). Anemia persisted as the most common laboratory finding in the postoperative evaluation. Conclusion: Our study identified comorbid chronic medical conditions, neurological complications because of IE, postoperative impaired left ventricular function, and treatment strategies such as monotherapy as poor prognostic factors in patients who underwent surgical treatment for IE. The management of IE is observed to be complex in the presence of comorbidities and complications, adversely affecting both survival and quality of life.

PA-MSHA improves prognosis of patients undergoing radical cystectomy: a retrospective cohort study using inverse probability of treatment weighting.

To observe the effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the prognosis and the incidence of lymphatic leakage in patients undergoing radical cystectomy (RC). A total of 129 patients who underwent RC in Lanzhou University Second Hospital from 2013 to 2022 were enrolled in this study. They were divided into 43 patients treated with PA-MSHA and 86 patients in the control group. Inverse probability of treatment weighting (IPTW) was applied to reduce potential selection bias. Kaplan-Meier method and Cox regression analysis were used to analyze the effect of PA-MSHA on the survival of patients and the incidence of postoperative lymphatic leakage. The PA-MSHA group exhibited improved overall survival (OS) and cancer-specific survival (CSS) rates compared to the control group. The 3-year and 5-year overall survival (OS) rates for the PA-MSHA group were 69.1% and 53.2%, respectively, compared to 55.6% and 45.3% for the control group (Log-rank=3.218, P=0.072). The 3-year and 5-year cancer-specific survival (CSS) rates for the PA-MSHA group were 73.3% and 56.5%, respectively, compared to 58.0% and 47.3% for the control group (Log-rank=3.218, P=0.072). Additionally, the 3-year and 5-year progression-free survival (PFS) rates for the PA-MSHA group were 74.4% and 56.8%, respectively, compared to 57.1% and 52.2% for the control group (Log-rank=2.016, P=0.156). Multivariate Cox regression analysis indicates that lymph node metastasis and distant metastasis are poor prognostic factors for patients, while the use of PA-MSHA can improve patients' OS (HR: 0.547, 95%CI: 0.304-0.983, P=0.044), PFS (HR: 0.469, 95%CI: 0.229-0.959, P=0.038) and CSS (HR: 0.484, 95%CI: 0.257-0.908, P=0.024). The same trend was observed in the cohort After IPTW adjustment. Although there was no significant difference in the incidence of postoperative lymphatic leakage [18.6% (8/35) vs. 15.1% (84.9%), P=0.613] and pelvic drainage volume [470 (440) ml vs. 462.5 (430) ml, P=0.814] between PA-MSHA group and control group, PA-MSHA could shorten the median retention time of drainage tube (7.0 d vs 9.0 d) (P=0.021). PA-MSHA may improve radical cystectomy in patients with OS, PFS, and CSS, shorten the pelvic drainage tube retention time.

The treatment of patients with chronic myeloid leukemia chronic phase combined with myelofibrosis with tyrosine kinase inhibitors: A Chinese population-based study.

e18524 Background: Chronic myeloid leukemia (CML) is a type of hematological malignancy characterized by the excessive proliferation of myeloid cells. Studies have shown that the presence of MF in CML patients has been associated with TFR. Identifying and assessing MF in CML patients at the time of diagnosis can provide valuable information for treatment planning and prognostic evaluation. Methods: The study enrolled 1757 CML-CP patients with pathological results of bone marrow biopsy. Patients with incomplete information from laboratory tests and medical records were excluded. The study was approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine and conducted in accordance with the Declaration of Helsinki. CML was diagnosed according to National Comprehensive Cancer Network (NCCN) 2023 version. Results: Patients with MF were found to be older (p&lt;0.001) and had higher leukocyte (p&lt;0.001) and platelet counts (p&lt;0.001). They were also more likely to experience anemia (p&lt;0.001), splenomegaly (p&lt;0.001), patients with myelofibrosis had a higher percentage of eosinophils (p&lt;0.001) and basophils (p&lt;0.001) and had a higher proportion of peripheral blood blast cells (p&lt;0.001) compared to patients without myelofibrosis. However, there was no significant difference in the male-to-female ratio between the two groups (p=0.690). Patients with MF were more unlikely to achieve certain treatment milestones, including a 3-month early molecular response (3M-EMR) (p&lt;0.001), 6-month BCR-ABLIS ≤ 1% (p&lt;0.001), and 12-month major molecular response (12M-MMR) (p&lt;0.001). The proportion of medium/high-risk patients, as determined by Sokal score (p&lt;0.001), Hasford score (p&lt;0.001), ELTS score (p&lt;0.001), and EUTOS score (p=0.002), was significantly increased in patients with MF (Table 1). Patients with MF had lower OS and PFS compared to patients without MF, indicating a potentially worse prognosis for those with MF. Patients with MF 10-year cumulative incidences of imatinib-therapy failure (p&lt;0.001). However, there was no statistically significant difference in the treatment failure rate with different second-generation TKIs (p=0.222). CML-CP patients with MF who were treated with different TKIs were found that second-generation TKIs were more likely to achieve a 3-month EMR(p=0.009), 6-month BCR-ABLIS ≤ 1% (p=0.019), and 12-month MMR(p=0.015) compared to imatinib. Conclusions: Based on the available data, the results suggest that MF is indeed a poor prognostic factor for patients with CML. This finding highlights the importance of considering MF as a factor in assessing the outlook for CML patients. These findings indicate that second-generation TKIs are more effective in achieving molecular responses compared to imatinib, particularly in the context of myelofibrosis.

Clinical significance of HER2 expression between primary tumors and metastatic lymph nodes in patients with extramammary Paget's disease.

e21568 Background: HER2 has been reported to be a potential oncogene and therapeutic target in extramammary Paget's disease (EMPD). However, the expression of HER2 in EMPD, especially in matched metastatic lymph nodes (LNs), is limited. Here, we investigated the heterogeneity of HER2 expression between primary tumors and positive nodes and its clinical significance in advanced EMPD patients and detected the efficacy of HER2-targeted antibody drug conjugates (ADCs) in EMPD. Methods: A total of 170 patients with pathologically confirmed EMPD of the scrotum and/or penis treated at SYSUCC from 2003 to 2023 were included. HER2 IHC staining (anti-HER2/neu (4B5), Ventana) and scoring were performed according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2023 guidelines. Outcome relationships were explored using Cohen's kappa coefficient, multivariate Cox regression and log-rank analysis. Results: A total of 102 primary tumor and 32 metastatic specimens were ultimately subjected to HER2 IHC staining. HER2 high-expression (IHC: 2/3+) was detected in 71.6% (0: 9.8%, 1+: 18.6%, 2+: 40.2% and 3+: 31.4%) and 68.8% (0: 21.9%, 1+: 9.4%, 2+: 28.1% and 3+: 40.6%) of the primary tumors and metastatic LNs, respectively. HER2-high EMPD patients experienced poorer outcomes, with a 5-year OS of 56.5%, than did HER2-low patients (P = 0.032). A multivariate Cox regression model showed that a positive lymph node (HR 15.39, 95% CI 3.79~62.43; P &lt; 0.001) and HER2 high-expression in primary tumors (HR 3.68, 95% CI 1.49~9.09; P = 0.005) were independent poor prognostic factors. Notably, in 31 paired samples, 35.5% (n = 11) of patients had inconsistent HER2 expression between primary tumors and corresponding lymph node metastases. Six (19.4%) patients exhibited a shift from high expression of HER2 in primary tumors to low expression of HER2 in the lymph nodes, and 5 (16.1%) patients exhibited the reverse change. Advanced EMPD patients with HER2 high-expression were treated with Disitamab Vedotin (RC48), for which the ORR was 80% and the DCR was 100% (n = 5). No adverse events (AEs) above grade 3-4 were observed. Conclusions: HER2 was highly expressed in both primary and metastatic LNs in EMPD patients. However, there was some heterogeneity in HER2 expression between paired primary and corresponding metastatic LNs. The expression status of HER2 should be evaluated in both primary tumors and corresponding lymph node metastases. A positive lymph node and HER2 high-expression are poor prognostic factors in patients with EMPD. RC48 demonstrated significant efficacy in treating patients with HER2-high advanced EMPD and has promising potential that requires further validation.