Risk Factors for Unplanned Early Implantable Port Catheter Removal in Adult Hematology Cancer Patients Receiving Chemotherapy: A Propensity Score Matching Study.

Purpose: Implantable port catheter is a reliable vascular access for chemotherapy infusion in cancer patients. However, patients with hematology malignancies usually present with a myriad of blood cell abnormalities that put them at risk of infection and mechanical problems requiring catheter removal. This study aims to determine the risk factors associated with unplanned (catheter removal other than completion of treatment plan) early (within 90 days of catheter implantation) implantable port catheter removal. Patients and Methods: A retrospective, propensity score-matched study of 386 patients with hematology malignancies who received implantable venous access ports between January 2015 and December 2022. We conducted a univariate analysis to select the variables for propensity score matching. Patients with unplanned early implantable port catheter removal (early group) were matched 1:1 to patients without unplanned early removal (non-early group). Results: Univariate analysis demonstrated a statistically significant difference between early and non-early groups for age (p = 0.048), hemoglobin level (p = 0.028), thrombocytopenia (p = 0.025), and PG-SGA (p < 0.001). Thrombocytopenia was the only independent risk factor with a statistically significant difference in Cox proportional hazard analysis, HR 2.823, 95 CI 1.050-7.589, p = 0.040. The median catheter survival for patients with thrombocytopenia was 61 days (95% CI 28.58-93.42) compared to 150 days (95% CI 9.81-290.19) for patients without thrombocytopenia, p = 0.015. Patient survival is not affected by early catheter removal. The median survival for patients in the early group was 28.28 months (95% CI 27.43-29.15) compared to 32.39 months (95% CI 24.11-40.68), for the non-early group, p = 0.709. Conclusion: Hematology malignancy patients with thrombocytopenia are at high risk for unplanned early port catheter removal without survival difference.

The associates of anxiety among lung cancer patients: Dehydroepiandrosterone (DHEA) as a potential biomarker.

OBJECTIVE: Anxiety is a prevalent comorbidity in lung cancer (LC) patients associated with a decline in quality of life. Dehydroepiandrosterone (DHEA), a neuroactive steroid, levels rise in response to stress. Prior research on the association between DHEA and anxiety has yielded contradictory results and no study has investigated this association in LC patients. METHODS: A total of 213 patients with LC were recruited from a general hospital. Data on demographic and cancer-related variables were collected. Using the Chinese version of the Hospital Anxiety and Depression Scale (HADS), the degree of anxiety was determined. Cortisol, DHEA, and Dehydroepiandrosterone sulfate (DHEA-S) levels in saliva were measured. Adjusting for confounding variables, a multivariate regression analysis was conducted. RESULTS: 147 men and 66 women comprised our group with an average age of 63.75 years. After accounting for demographic and treatment-related factors, anxiety levels were significantly correlated with, post-traumatic stress symptoms (PTSSs) (ß = 0.332, p < 0.001) and fatigue (ß = 0.247, p = 0.02). Association between anxiety and three factors, including DHEA, PTSSs, and fatigue, was observed in patients with advanced cancer stages (III and IV) (DHEA ß = 0.319, p = 0.004; PTSS ß = 0.396, p = 0.001; fatigue ß = 0.289, p = 0.027) and those undergoing chemotherapy (DHEA ß = 0.346, p = 0.001; PTSS ß = 0.407, p = 0.001; fatigue ß = 0.326, p = 0.011). CONCLUSIONS: The association between anxiety and DHEA remained positive in advanced cancer stages and chemotherapy patients. Further study is necessary to determine whether DHEA is a potential biomarker of anxiety in LC patients.

Radiation-induced skin and heart toxicity in patients with breast cancer treated with adjuvant proton radiotherapy: a comparison with photon radiotherapy.

This study aimed to investigate the dose parameters and incidence of radiotherapy (RT)-associated toxicity in patients with left breast cancer (LBC) treated with proton-RT, compared with photon-RT. We collected data from 111 patients with LBC who received adjuvant RT in our department between August 2021 and March 2023. Among these patients, 24 underwent proton-RT and 87 underwent photon-RT. In addition to the dosimetric analysis for organs at risk (OARs), we measured NT-proBNP levels before and after RT. Our data showed that proton-RT improved dose conformity and reduced doses to the heart and lungs and was associated with a lower rate of increased NT-proBNP than did photon-RT. Regarding skin toxicity, the Dmax for 1 c.c. and 10 c.c. and the average dose to the skin-OAR had predictive roles in the risk of developing radiation-induced dermatitis. Although pencil beam proton-RT with skin optimization had a dose similar to that of skin-OAR compared with photon-RT, proton-RT still had a higher rate of radiation dermatitis (29%) than did photon RT (11%). Using mice 16 days after irradiation, we demonstrated that proton-RT induced a greater increase in interleukin 6 and transforming growth factor-ß1 levels than did photon-RT. Furthermore, topical steroid ointment reduced the inflammatory response and severity of dermatitis induced by RT. In conclusion, we suggest that proton-RT with skin optimization spares high doses to OARs with acceptable skin toxicity. Furthermore, prophylactic topical steroid treatment may decrease radiation dermatitis by alleviating proton-induced inflammatory responses in vivo.

YTHDF3 Modulates EGFR/ATK/ERK/p21 Signaling Axis to Promote Cancer Progression and Osimertinib Resistance of Glioblastoma Cells.

BACKGROUND/AIM: Despite recent advances in EGFR-tyrosine kinase inhibitor (TKI) drugs for glioblastoma multiforme (GBM), intrinsic EGFR alterations in GBM have resulted in drug resistance and unsatisfactory clinical development of EGFR-TKIs. Determining the unknown mechanisms underlying EGFR-TKI drug resistance is an urgent, but unmet, medical need for GBM. Although several m6A RNA methylation regulators, such as reader YTHDF1/2, were recently predicted to be related to GBM recurrence, none was associated with resistance to the 3rd generation EGFR-TKI osimertinib. MATERIALS AND METHODS: Osimertinib-resistant GBM cells (U87OSR) were established to ascertain the correlation between m6A expression and osimertinib resistance, prior to systemic analyses on m6A writers, erasers, and readers. YTHDF3-silencing was employed to reveal changes in IC50, cellular migration, cancer stemness, and p21-guided senescence in U87OSR cells. Signaling pathways and an in vivo xenograft model of U87OSR cells were investigated to delineate the influence of osimertinib-resistance and elevated YTHDF3 expression. RESULTS: YTHDF3 played a crucial role in inducing cellular proliferation, migration, and stemness in U87OSR GBM cells. Importantly, silencing of YTHDF3 markedly reduced the activation of certain signaling pathways, including EGFR- or ITGA7- AKT, and ERK in U87OSR cells. Our study also revealed the oncogenic function of YTHDF3 in inducing senescence escape via p21 down-regulation. In contrast, silencing of YTHDF3 resulted in increased p21 expression, senescence, and suppressed tumor growth in our osimertinib-resistant preclinical model. CONCLUSION: Overall, our research underscores the novel potential of YTHDF3 as a new pharmacological target in GBM treatment, specifically for patients with osimertinib-resistant or refractory tumors.

Cytokine-Induced Myeloid-Derived Suppressor Cells Demonstrate Their Immunoregulatory Functions to Prolong the Survival of Diabetic Mice.

Type 1 diabetes is an inflammatory state. Myeloid-derived suppressive cells (MDSCs) originate from immature myeloid cells and quickly expand to control host immunity during infection, inflammation, trauma, and cancer. This study presents an ex vivo procedure to develop MDSCs from bone marrow cells propagated from granulocyte-macrophage-colony-stimulating factor (GM-CSF), interleukin (IL)-6, and IL-1ß cytokines expressing immature morphology and high immunosuppression of T-cell proliferation. The adoptive transfer of cytokine-induced MDSCs (cMDSCs) improved the hyperglycemic state and prolonged the diabetes-free survival of nonobese diabetic (NOD) mice with severe combined immune deficiency (SCID) induced by reactive splenic T cells harvested from NOD mice. In addition, the application of cMDSCs reduced fibronectin production in the renal glomeruli and improved renal function and proteinuria in diabetic mice. Moreover, cMDSCs use mitigated pancreatic insulitis to restore insulin production and reduce the levels of HbA1c. In conclusion, administering cMDSCs propagated from GM-CSF, IL-6, and IL-1ß cytokines provides an alternative immunotherapy protocol for treating diabetic pancreatic insulitis and renal nephropathy.

The relationship of nutritional status with anticancer immunity and its prognostic value for head and neck cancer.

Malnutrition has been reported to be associated with reduced survival and deficient anticancer immunity, and undernourishment is a frequent comorbidity in head and neck cancer (HNC) patients. In this study, we evaluated the relationship between nutritional status and immunologic factors, and its prognostic value for HNC. We retrospectively reviewed 212 HNC patients who had undergone a nutrition evaluation based on the Patient-Generated Subjective Global Assessment (PG-SGA) and curative radiotherapy (RT). The role of nutritional status in the prognosis of HNC and its correlation with anticancer immune response was assessed in HNC patients, and in the 4-nitroquinoline 1-oxide (4NQO)-induced tongue tumor animal model. Our data revealed that malnutrition (high PG-SGA scores) was significantly associated with more advanced disease, lower body mass index, lower RT completion rates, and reduced survival. Patients in the group with high PG-SGA scores had a higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived suppressor cells (MDSCs), and elevated IL-6 levels in the peripheral circulation. Patients with increased PG-SGA scores following treatment were more likely to developing locoregional failure. In the 4NQO-induced tumor model, nutritional supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. Following ectopic tumor implantation in an immunocompetent host, nutrition supplements decreased tumor growth in association with attenuated MDSC recruitment and lower IL-6 expression. In conclusion, malnutrition by PG-SGA was associated with poor prognosis in HNC patients. Based on the data of HNC patients and the 4NQO-tumor model, adequate nutritional supplementation might improve the prognosis associated with augmented anticancer immunity.

Dickkopf-1 Acts as a Profibrotic Mediator in Progressive Chronic Kidney Disease.

Chronic kidney disease (CKD) is a serious public health problem. Due to a high variability in the speed of CKD progression to end-stage renal disease (ESRD) and the critical involvement of Wnt/ß-catenin signaling in CKD, we investigated the role of the Wnt antagonist Dickkopf-1 (DKK1) in CKD progression. Our data revealed that patients with CKD stages 4-5 had higher DKK1 levels in their serum and renal tissues than the control subjects. In an 8-year follow-up, the serum DKK1-high group in the enrolled CKD patients showed a faster progression to ESRD than the serum DKK1-low group. Using a rat model of 5/6 nephrectomy (Nx)-induced CKD, we consistently detected elevated serum levels and renal production of DKK1 in 5/6 Nx rats compared to sham-operated rats. Importantly, the knockdown of the DKK1 levels in the 5/6 Nx rats markedly attenuated the CKD-associated phenotypes. Mechanistically, we demonstrated that the treatment of mouse mesangial cells with recombinant DKK1 protein induced not only the production of multiple fibrogenic proteins, but also the expression of endogenous DKK1. Collectively, our findings suggest that DKK1 acts as a profibrotic mediator in CKD, and elevated levels of serum DKK1 may be an independent predictor of faster disease progression to ESRD in patients with advanced CKD.

Insights into the Molecular Mechanisms of NRF2 in Kidney Injury and Diseases.

Redox is a constant phenomenon in organisms. From the signaling pathway transduction to the oxidative stress during the inflammation and disease process, all are related to reduction-oxidation (redox). Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor targeting many antioxidant genes. In non-stressed conditions, NRF2 maintains the hemostasis of redox with housekeeping work. It expresses constitutively with basal activity, maintained by Kelch-like-ECH-associated protein 1 (KEAP1)-associated ubiquitination and degradation. When encountering stress, it can be up-regulated by several mechanisms to exert its anti-oxidative ability in diseases or inflammatory processes to protect tissues and organs from further damage. From acute kidney injury to chronic kidney diseases, such as diabetic nephropathy or glomerular disease, many results of studies have suggested that, as a master of regulating redox, NRF2 is a therapeutic option. It was not until the early termination of the clinical phase 3 trial of diabetic nephropathy due to heart failure as an unexpected side effect that we renewed our understanding of NRF2. NRF2 is not just a simple antioxidant capacity but has pleiotropic activities, harmful or helpful, depending on the conditions and backgrounds.

Anterior gradient 2 induces resistance to sorafenib via endoplasmic reticulum stress regulation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for almost 80% of all liver cancer cases and is the sixth most common cancer and the second most common cause of cancer-related death worldwide. The survival rate of sorafenib-treated advanced HCC patients is still unsatisfactory. Unfortunately, no useful biomarkers have been verified to predict sorafenib efficacy in HCC. RESULTS: We assessed a sorafenib resistance-related microarray dataset and found that anterior gradient 2 (AGR2) is highly associated with overall and recurrence-free survival and with several clinical parameters in HCC. However, the mechanisms underlying the role of AGR2 in sorafenib resistance and HCC progression remain unknown. We found that sorafenib induces AGR2 secretion via posttranslational modification and that AGR2 plays a critical role in sorafenib-regulated cell viability and endoplasmic reticulum (ER) stress and induces apoptosis in sorafenib-sensitive cells. In sorafenib-sensitive cells, sorafenib downregulates intracellular AGR2 and conversely induces AGR2 secretion, which suppresses its regulation of ER stress and cell survival. In contrast, AGR2 is highly intracellularly expressed in sorafenib-resistant cells, which supports ER homeostasis and cell survival. We suggest that AGR2 regulates ER stress to influence HCC progression and sorafenib resistance. CONCLUSIONS: This is the first study to report that AGR2 can modulate ER homeostasis via the IRE1α-XBP1 cascade to regulate HCC progression and sorafenib resistance. Elucidation of the predictive value of AGR2 and its molecular and cellular mechanisms in sorafenib resistance could provide additional options for HCC treatment.

Therapeutic Potential of Extracts from Macaranga tanarius (MTE) in Diabetic Nephropathy.

Diabetic nephropathy is a complication of diabetes that leads to end-stage kidney disease and is a major health burden worldwide. Prenylflavonoid compounds extracted from Macaranga tanarius (MTE) exhibit anti-inflammation, anti-oxidant, and anti-bacterial properties. However, the effects of these compounds on diabetic nephropathy remain unclear. The effects of MTE on diabetic nephropathy were investigated in vitro by using mouse renal mesangial cells and in vivo by using a db/db knockout mouse model. No overt alteration in proliferation was observed in mouse renal mesangial cells treated with 0-1 µg/mL MTE. Western blot analysis indicated that MTE dose-dependently attenuated the expression of fibronectin, α-smooth muscle actin, and collagen IV. Administration of MTE ameliorated renal albumin loss in db/db mice. Immunohistochemical staining revealed that MTE mitigated diabetes-induced fibronectin and collagen IV expression. Periodic acid-Schiff (PAS) and trichrome staining also showed that administration of MTE reduced the renal fibrosis phenomenon. MTE significantly ameliorated diabetes-induced nephropathy.

Cognitive function and breast cancer molecular subtype before and after chemotherapy.

Chemotherapy-related cognitive impairment has been reported in patients with breast cancer and received growing attention due to increased survival rate. However, cognitive outcome according to pathological tumor features, especially human epidermal growth factor receptor (HER2) status, has not been clearly elucidated. Despite its potential link with cognitive status through neuroinflammatory response, existing research is sparse and limited to cross-sectional studies. In this observational cohort study, 52 breast cancer patients received a series of neuropsychological examinations before and after chemotherapy. Patients' performances were compared with normative data, and analyzed with Reliable Change Indices and mixed-model analysis of covariance. Results showed that there was a higher percentage of HER2+ patients than HER2- patients who showed defective attention and processing speed before chemotherapy, and that there were more patients with HER2+ status showing cognitive decline on tests of attention and executive functions following chemotherapy. Group-wise analyses confirmed the foregoing pattern and further revealed that patients with HER2+ status also tended to deteriorate more in verbal memory after chemotherapy. These findings indicate that HER2 overexpression may serve as prognostic factors that help explain the heterogeneous cognitive outcome in breast cancer survivors. Further studies are needed to replicate this finding and delineate the underlying mechanisms.

Roles of protein tyrosine phosphatases in hepatocellular carcinoma progression (Review).

Hepatocellular carcinoma (HCC) represents almost 80% of all liver cancers, is the sixth most common cancer and is the second­highest cause of cancer­related deaths worldwide. Protein tyrosine phosphatases (PTPs), which are encoded by the largest family of phosphatase genes, play critical roles in cellular responses and are implicated in various signaling pathways. Moreover, PTPs are dysregulated and involved in various cellular processes in numerous cancers, including HCC. Kinases and phosphatases are coordinators that modulate cell activities and regulate signaling responses. There are multiple interacting signaling networks, and coordination of these signaling networks in response to a stimulus determines the physiological outcome. Numerous issues, such as drug resistance and inflammatory reactions in the tumor microenvironment, are implicated in cancer progression, and the role of PTPs in these processes has not been well elucidated. Therefore, the present review focused on discussing the relationship of PTPs with inflammatory cytokines and chemotherapy/targeted drug resistance, providing detailed information on how PTPs can modulate inflammatory reactions and drug resistance to influence progression in HCC.

Effect of Proton Therapy on Tumor Cell Killing and Immune Microenvironment for Hepatocellular Carcinoma.

Radiotherapy with proton therapy (PT) has dosimetric advantages over photon therapy, which helps to enlarge the therapeutic window of radiotherapy for hepatocellular carcinoma (HCC). We evaluated the response of HCC to PT and examined the underlying mechanisms. The human liver cancer cell lines HepG2 and HuH7 and the murine liver cancer cell line Hepa1-6 were selected for cell and animal experiments to examine the response induced by PT irradiation. Biological changes and the immunological response following PT irradiation were examined. In vitro experiments showed no significant difference in cell survival following PT compared with photon radiotherapy. In a murine tumor model, the tumors were obviously smaller in size 12 days after PT irradiation. The underlying changes included increased DNA damage, upregulated IL-6 levels, and a regulated immune tumor microenvironment. Protein analysis in vitro and in vivo showed that PT increased the level of programmed cell death ligand 1 (PD-L1) expressed in tumor cells and recruited myeloid-derived suppressor cells (MDSCs). The increase in PD-L1 was positively correlated with the irradiation dose. In Hepa1-6 syngeneic mouse models, the combination of PT with anti-PD-L1 increased tumor growth delay compared with PT alone, which was associated with increased tumor-infiltrating T cells and attenuated MDSC recruitment in the microenvironment. Furthermore, when PT was applied to the primary HCC tumor, anti-PD-L1 antibody-treated mice showed smaller synchronous unirradiated tumors. In conclusion, the response of HCC to PT was determined by tumor cell killing and the immunological response in the tumor microenvironment. The combination with the anti-PD-L1 antibody to enhance antitumor immunity was responsible for the therapeutic synergism for HCC treated with PT. Based on our results, we suggest that PT combined with anti-PD-L1 may be a promising therapeutic policy for HCC.

Immune Modulation by Myeloid-Derived Suppressor Cells in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) frequently leads to end-stage renal disease and other life-threatening illnesses. The dysregulation of glomerular cell types, including mesangial cells, endothelial cells, and podocytes, appears to play a vital role in the development of DKD. Myeloid-derived suppressor cells (MDSCs) exhibit immunoregulatory and anti-inflammatory properties through the depletion of L-arginine that is required by T cells, through generation of oxidative stress, interference with T-cell recruitment and viability, proliferation of regulatory T cells, and through the promotion of pro-tumorigenic functions. Under hyperglycemic conditions, mouse mesangial cells reportedly produce higher levels of fibronectin and pro-inflammatory cytokines. Moreover, the number of MDSCs is noticeably decreased, weakening inhibitory immune activities, and creating an inflammatory environment. In diabetic mice, immunotherapy with MDSCs that were induced by a combination of granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1ß, and IL-6, reduced kidney to body weight ratio, fibronectin expression, and fibronectin accumulation in renal glomeruli, thus ameliorating DKD. In conclusion, MDSCs exhibit anti-inflammatory activities that help improve renal fibrosis in diabetic mice. The therapeutic targeting of the proliferative or immunomodulatory pathways of MDSCs may represent an alternative immunotherapeutic strategy for DKD.

Role of vitamin D3 in tumor aggressiveness and radiation response for hepatocellular carcinoma.

Locoregional control is a significant prognostic factor for hepatocellular carcinoma (HCC). Historically, the use of radiotherapy (RT) for HCC was limited owing to the low radiotolerance of the liver and the need for high RT doses for disease control. We aimed to examine if 1α,25-dihydroxyvitamin D3 (calcitriol) has a role in the tumor inhibition and the radiation response of HCC in vitro and in vivo, and explore the underlying mechanisms. The human and murine liver cancer cell lines were selected for cellular and animal experiments to investigate the changes in tumor characteristics and the radiation response after calcitriol supplementation. The effects induced by calcitriol supplementation on interleukin-6 (IL-6) signaling and the tumor immune microenvironment following RT were also examined. Our data revealed that calcitriol supplementation attenuated tumor aggressive behavior, decrease IL-6 expression, and augmented radiation-induced tumor inhibition. The biological changes following calcitriol treatment included suppressed epithelial-mesenchymal transition, attenuated cancer stem cell-like properties and increased radiation-induced reactive oxygen species and cell death in vitro. Regarding immune microenvironment, calcitriol attenuated the recruitment of myeloid-derived suppressor cell (MDSC) recruitment and increased the infiltration of cytotoxic T cells in tumor following RT. Furthermore, When the primary liver tumor was irradiated with larger dose per fraction, calcitriol induced a smaller size of synchronous unirradiated tumor in mice, which linked with attenuated IL-6 signaling and MDSC recruitment. In conclusion, calcitriol treatment reduced tumor aggressiveness and enhanced the radiation response. The inhibited IL-6 signaling and subsequently enhanced antitumor immunity might be responsible to augment radiation-induced tumoricidal effect induced by calcitriol. Based on our results, we suggest that calcitriol could exert the antitumor and radiosensitization effects for HCC, especially for multifocal tumors.

Investigation of a Novel Acoustic Levitation Technique Using the Transition Period Between Acoustic Pulse Trains and Electrical Driving Signals.

Acoustic levitation is considered one of the most effective noncontact particle manipulation methods, along with aerodynamic, ferromagnetic, and optical levitation techniques. It is not restricted by the material properties of the target. However, existing acoustic levitation techniques have some drawbacks that limit their potential applications. Therefore, in this article, an innovative approach is proposed to manipulate objects more intuitively and freely. By taking advantage of the transition periods between the acoustic pulse trains and electrical driving signals, acoustic traps can be created by switching the acoustic focal spots rapidly. Since the high-energy-density points are not formed simultaneously, the computation of the acoustic field distribution with complicated mutual interference can be eliminated. Therefore, compared to the existing approaches that created acoustic traps by solving pressure distributions using iterative methods, the proposed method simplifies the computation of time delay and makes it possible to be solved even with a microcontroller. In this work, three experiments have been demonstrated successfully to prove the capability of the proposed method including lifting a Styrofoam sphere, transportation of a single target, and suspending two objects. Besides, simulations of the distributions of acoustic pressure, radiation force, and Gor'kov potential were conducted to confirm the presence of acoustic traps in the scenarios of lifting one and two objects. The proposed tactic should be considered effective since the results of the practical experiments and simulations support each other.

Role of Nutritional Status in the Treatment Outcome for Esophageal Squamous Cell Carcinoma.

Undernourishment is reported to impair treatment response, further leading to poor prognosis for cancer patients. We aimed to investigate the role of nutritional status on the prognosis of squamous cell carcinoma (SCC) of the esophagus, and its correlation with anticancer immune responsiveness. We retrospectively reviewed 340 esophageal-SCC patients who completed curative treatment and received a nutrition evaluation by the Patient-Generated Subjective Global Assessment (PGSGA) score at the beginning and completion of neoadjuvant treatment at our hospital. The correlation between the nutritional status and various clinicopathological parameters and prognosis were examined. In addition, the role of nutritional status in the regulation of the anticancer immune response was also assessed in cancer patients and in a 4-nitroquinoline 1-oxide (4NQO)-induced esophageal tumor model. Our data revealed that malnutrition (patients with a high PGSGA score) was associated with advanced stage and reduced survival rate. Patients in the group with a high PGSGA score were correlated with the higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived-suppressor cells (MDSC) and increased IL-6 level. Furthermore, surgical resection brought the survival benefit to patients in the low PGSGA group, but not for the malnourished patients after neoadjuvant treatment. Using a 4NQO-induced tumor model, we found that nutrition supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. In conclusion, malnutrition was associated with poor prognosis in esophageal-SCC patients. Nutritional status evaluated by PGSGA may be useful to guide treatment decisions in clinical practice. Nutritional supplementation is suggested to improve prognosis, and it might be related to augmented anticancer immune response.

Nutrition Assessment and Adverse Outcomes in Hospitalized Patients with Tuberculosis.

BACKGROUND: Malnutrition in patients with tuberculosis (TB) is associated with poor outcomes. This study assessed the validity of the patient-generated subjective global assessment (PG-SGA) in adult TB patients and examined the association of the PG-SGA score with adverse outcomes. METHODS: This is a retrospective chart review study compared with the well-nourished and malnourished TB patients. The nutritional status was determined using the PG-SGA for adult patients (n = 128). Clinical outcomes included liver injury and mortality. Adverse outcomes included hepatitis during anti-tuberculosis therapy. RESULTS: By comparing nutritional status using global assessment, well-nourished patients had a significantly higher body weight index (p = 0.002), a lower PG-SGA score (p < 0.001), and lower diabetic rate (p = 0.029). Malnourishment was a risk factor (p = 0.022) for liver injury and fatal outcomes (p < 0.001). A higher PG-SGA score was a risk factor for liver injury (p = 0.002) and an independent risk factor for fatal outcomes (p = 0.031). ROC analysis for outcome prediction showed that a PG-SGA score of 5.5 points yielded the most appropriate sensitivity (61.5%) and specificity (64.7%). CONCLUSION: Both global assessment and the total PG-SGA score were related to tuberculosis outcome and liver injury during anti-TB treatment.

Circulating cytokines as predictors of depression in patients with breast cancer.

Depression is a common comorbid disorder associated with breast cancer, and it can have considerable physical and psychological impacts. Circulating cytokines have been proposed as a potential tool to predict depression in various diseases; however, limited studies have specifically examined it in breast cancer. In this study, we examined and compared the prediction ability of various circulating cytokines for depression in patients with breast cancer. Eighty-three patients with a new diagnosis of breast cancer not receiving chemotherapy were recruited; among them, 15 patients had depression and 68 did not have depression. Depression was evaluated using the Patient Health Questionnaire 9 (PHQ-9). Cytokine levels in the serum were measured using an immunology multiplex assay. Two types of cytokines were assayed: (1) proinflammatory cytokines (interleukin [IL]-1ß, IL-2, IL-6, IL-12, IL-17A, interferon [IFN]γ, and tumor necrosis factor [TNF]α) and (2) anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). Receiver operating characteristic (ROC) analysis was performed to calculate the area under the curves (AUCs), sensitivities, and specificities of circulating cytokines for predicting depression. As a result, IL-2 (AUC = 0.78) and IL-5 (AUC = 0.76) demonstrated good predictability for depression, even after controlling for the covariates (i.e. age, education, stage of cancer, surgery, radiation therapy, and hormone therapy). The optimal cut-off value of IL-2 for predicting depression was 1.06 pg/mL with a sensitivity of 86.7% and a specificity of 52.9%; this cytokine also had the best prediction ability in this study. Owing to the prediction ability and practical feasibility of circulating cytokines, they may be used as a valid laboratory diagnostic tool for depression in breast cancer.