Negative Prognostic Predictor Research Articles

DNAJC1 facilitates glioblastoma progression by promoting extracellular matrix reorganization and macrophage infiltration

BackgroundGlioblastoma (GBM) is a high-grade and heterogeneous subtype of glioma that presents a substantial challenge to human health, characterized by a poor prognosis and low survival rates. Despite its known involvement in regulating leukemia and melanoma, the function and mechanism of DNAJC1 in GBM remain poorly understood.MethodsUtilizing data from the TCGA, CGGA, and GEO databases, we investigated the expression pattern of DNAJC1 and its correlation with clinical characteristics in GBM specimens. Loss-of-function experiments were conducted to explore the impact of DNAJC1 on GBM cell lines, with co-culture experiments assessing macrophage infiltration and functional marker expression.ResultsOur analysis demonstrated frequent overexpression of DNAJC1 in GBM, significantly associated with various clinical characteristics including WHO grade, IDH status, chromosome 1p/19q codeletion, and histological type. Moreover, Kaplan‒Meier and ROC analyses revealed DNAJC1 as a negative prognostic predictor and a promising diagnostic biomarker for GBM patients. Functional studies indicated that silencing DNAJC1 impeded cell proliferation and migration, induced cell cycle arrest, and enhanced apoptosis. Mechanistically, DNAJC1 was implicated in stimulating extracellular matrix reorganization, triggering the epithelial-mesenchymal transition (EMT) process, and initiating immunosuppressive macrophage infiltration.ConclusionsOur findings underscore the pivotal role of DNAJC1 in GBM pathogenesis, suggesting its potential as a diagnostic and therapeutic target for this challenging disease.

A CASE OF CHRONIC PERICARDITIS IN A YOUNG PATIENT

Abstract A 25–year–old woman was admitted to our department with a diagnosis of pericarditis and pericardial effusion. She reported a flu episode 5 months earlier followed by persistent dry cough, dyspnoea on exertion and palpitations. Due to the persistence of symptoms, she consulted a cardiologist and it was observed a mild to moderate pericardial effusion with a raised C reactive protein at lab test. At first she was treated with ibuprofen and colchicine. After 2 months, prednisone was added to the therapy for effusion worsening. During steroids descalation she started complaining of night fever. Few weeks later an echocardiogram revealed increased pericardial effusion (21 mm) with signs of right atrial compression, so she was admitted to our department. No cardiovascular risk factors were reported but overweight and smoking habit. ECG at admission showed a slight depression of PR in inferior leads. Given the history, persistence of elevated inflammatory markers and fever on admission, despite prolonged therapy with NSAIDs, the patient was treated for high–risk pericarditis, with ibuprofen and colchicine. In addition, aetiological research was pursued: autoantibody and viral panel were negative; chest X–ray showed mediastinal enlargement and swelling in the right hilar region. So an urgent chest CT scan was performed and it showed a 8x9 cm mediastinal mass extending to the pectoral muscles and sternum. The mass biopsy revealed a classical Hodgkin lymphoma so she was transferred to Hematology department and chemotherapy was started. During her hospital stay, the effusion remained stable (17 mm). This clinical case demonstrates that pericarditis, even in a young patient, with a lack of response to NSAIDs therapy and with an unremitting course, must raise the suspicion of an occult cancer. In fact, according to the latest guidelines, in case of high–risk pericarditis, i.e. in the presence of at least one negative prognostic predictor between fever higher than 38°C, subacute onset, severe pericardial effusion, tamponade or failure of medical therapy after one week, aetiological research is indicated, in addition to hospitalization. It shouldn‘t be forgotten that pericarditis may be the first manifestation of an occult extracardiac tumor. In particular, the primary tumors associated with pericarditis are breast cancer, lung cancer and lymphomas. Probably better case management would have allowed an earlier diagnosis and treatment of our patient‘s cancer.

Prognostic Impact of the Immune-Cell Infiltrate in N1-Positive Non–Small-Cell Lung Cancer

IntroductionThe tumoral immune milieu plays a crucial role for the development of non–small-cell lung cancer (NSCLC) and may influence individual prognosis. We analyzed the predictive role of immune cell infiltrates after curative lung cancer surgery. Materials and MethodsThe tumoral immune-cell infiltrate from 174 patients with pN1 NSCLC and adjuvant chemotherapy was characterized using immunofluorescence staining. The density and distribution of specific immune cells in tumor center (TU), invasive front (IF) and normal tissue (NORM) were correlated with clinical parameters and survival data. ResultsTumor specific survival (TSS) of all patients was 69.9% at 5 years. The density of tumor infiltrating lymphocytes (TIL) was higher in TU and IF than in NORM. High TIL density in TU (low vs. high: 62.0% vs. 86.7%; p = .011) and the presence of cytotoxic T-Lymphocytes (CTLs) in TU and IF were associated with improved TSS (positive vs. negative: 90.6% vs. 64.7% p = .024). High TIL-density correlated with programmed death-ligand 1 expression levels ≥50% (p < .001). Multivariate analysis identified accumulation of TIL (p = .016) and low Treg density (p = .003) in TU as negative prognostic predictors in squamous cell carcinoma (p = .025), whereas M1-like tumor- associated macrophages (p = .019) and high programmed death-ligand 1 status (p = .038) were associated with better survival in adenocarcinoma. ConclusionThe assessment of specific intratumoral immune cells may serve as a prognostic predictor in pN1 NSCLC. However differences were observed related to adenocarcinoma or squamous cell carcinoma histology. Prospective assessment of the immune-cell infiltrate and further clarification of its prognostic relevance could assist patient selection for upcoming perioperative immunotherapies.

The flail-arm syndrome: the influence of phenotypic features

Objective: The flail-arm syndrome (FAS), one of the Amyotrophic lateral sclerosis (ALS) phenotypes, is characterized by slow progression and predominantly lower motor neuron (LMN) involvement with proximal upper limb (UL) weakness. We aim to characterize the clinical features, progression and survival of FAS associated with distal or proximal onset and presence or absence of upper motor neuron signs (UMN) signs at diagnosis. Methods: Data from 704 ALS patients was analyzed. Of the 190 patients with UL onset; 134 were excluded as not respecting the published criteria for FAS. The included patients were divided into four groups according to distal/proximal onset and presence/absence of UMN signs. Results: 56 FAS patients (8% of the population), median age at onset 59.9 years (Q1/Q3, 50.3–68.1), 75% men, were studied. Distal onset with UMN signs occurred in 37.5%, distal onset without UMN signs in 28.6%, proximal onset with UMN signs in 8.9% and proximal onset without UMN signs in 25%. Age of onset, sex, fasciculations at onset, diagnostic delay, progression rate, time to respiratory involvement and survival were similar among the four groups. Sex ratio was more balanced in patients with UMN signs (p = 0.032) and survival was shorter (69.5 months, 95% CI: 55.4–110.4 vs 152.6 months, 95% CI: 69.0–177.3; p = 0.035). The Cox regression identified rate of progression (p < 0.001) and UMN signs (p = 0.003) as independent predictors of shorter survival. Conclusions: Distal or proximal onset had no influence on clinical characteristics and prognosis but UMN signs at diagnosis are a negative prognostic predictor.

Nuclear factor erythroid-2-related factor 2 (Nrf2) is a potential prognostic factor in patients with gastric adenocarcinoma

BackgroundGastric cancer is one of the leading causes of cancer-related death, and many researchers are focused on the discovery and use of different biomarkers in prognosis prediction. The use of Nrf2 as a prognostic marker in patients with gastric cancer remains controversial. In this study, we evaluated the expression of Nrf2 protein in gastric adenocarcinoma. Patients and methodsA total of 86 patients who underwent gastric resection and D2 lymph node dissection due to gastric adenocarcinoma were included. Clinicopathological characteristics, such as age, gender, gastrectomy type, pathologic T (pT) and N (pN) stages, tumor grade, tumor type per Lauren’s classification, presence of lymphovascular invasion, and Nrf2 expression were evaluated. ResultsWhile pT, pN, and Nrf-2 expression were found to be negative prognostic predictors for overall survival in one-way analysis of variance, Nrf-2 expression was the only significant negative prognostic predictor in multivariance analysis. pT, pN, diffuse type, high tumor grade, and Nrf-2 expression significantly affected overall survival in Kaplan-Meier survival analyses (p = 0.02, p = 0.03, p < 0.01, p = 0.027, and p = 0.001, respectively). ConclusionsOur findings support that Nrf2 is a prognostic marker in patients with gastric adenocarcinoma. Anti-Nrf2 therapy options should be investigated to improve prognosis in gastric cancer patients.

Impact of Age of Onset on Survival after Hepatectomy for Patients with Colorectal Cancer Liver Metastasis: A Real-World Single-Center Experience.

The incidence of early-onset CRC is increasing. However, the effect of age of onset on the long-term outcome of colorectal cancer liver metastasis (CRLM) remains unclear. This study aimed to evaluate the association between the age of onset and the oncological outcome of CRLM patients and to investigate whether the prognostic role of RAS mutation is altered with age. We retrospectively investigated consecutive patients at our institution who underwent initial liver resection between 2006 and 2020. The inverse probability of treatment weighting (IPTW) method was used to balance the confounders among early- (≤45 years; EOCRLM), intermediate- (46-70 years; IOCRLM), and late-onset (>70 years; LOCRLM) groups. The prognostic role of RAS was assessed based on age group. A total of 1189 patients were enrolled: 162 in the EOCRLM group, 930 in the IOCRLM group, and 97 in the LOCRLM group. No difference in disease-free survival (DFS) was found between the three groups. However, EOCRLM were more likely to develop extrahepatic and extrapulmonary metastasis and had significantly lower five-year OS rates than IOCRLM. After IPTW, EOCRLM remained a negative prognostic predictor. RAS mutations were significantly associated with worse survival than wild-type RAS in EOCRLM and IOCRLM. However, RAS mutation did not predict the prognosis of patients with LOCRLM. Patients with EOCRLM had a significantly lower OS than IOCRLM patients and age influences the prognostic power of RAS status. These findings may be helpful for doctors to guide the clinical treatments and develop follow-up strategies.

Exploring the role of neutrophil-to-lymphocyte ratio and blood chemistry in head and neck adenoid cystic carcinomas treated with carbon ion radiotherapy

Background and purposeIn recent years, there is an emerging interest in the prognostic role of chemistry blood biomarkers in oncological patients but their role in adenoid cystic carcinomas (ACCs) is still unknown. This study aims to assess the prognostic significance of baseline neutrophil-to-lymphocyte ratio (NLR) and blood chemistry in a series of head and neck ACC patients treated with carbon ion radiotherapy (CIRT). Material and MethodsWe retrospectively retrieved the data of 49 consecutive head and neck ACC patients treated with CIRT. Univariable and multivariable Cox proportional hazard regression (Cox-ph) analyses were performed to look for a potential association of NLR, and other blood biomarker values, with disease-free survival (DFS), Local Control (LC), Metastasis Free Survival (MFS) and overall survival (OS). ResultsNo significant association between NLR > 2,5 and DFS, LC, MFS and OS was found with univariable analysis although a trend was reported for DFS (Hazard ratio [HR]: 2,10, 95 % CI: 0,85 – 5,08, p-value = 0,11). Patients with hemoglobin (hb) ≤ 14 g/dL showed significantly better DFS, MFS and OS. Multivariable regression Cox-ph analysis for DFS, adjusted for margin status, clinical target volume and Absolute Number of Monocytes, reported the following statistically significant HRs, for both NLR > 2,5 and hb > 14 g/dL respectively: 4,850 (95 % CI = 1,408 – 16,701, p = 0,012) and 3,032 (95 % CI = 1,095 – 8,393, p = 0,033). Moreover, hb > 14 with HR = 3,69 (95 % CI: 1,23 – 11,07, p-value = 0,02), was a negative independent prognostic predictor for MFS. ConclusionsPre-treatment NLR and hb values seem to be independent prognostic predictor for clinical outcomes in head and neck ACC patients. If their role will be validated in a larger prospective cohort, they might be worthwhile for a pre-treatment risk stratification in patients treated with CIRT.

Oncological outcomes of surgery for isolated retroperitoneal recurrence in renal cancer patients after radical nephrectomy.

Isolated retroperitoneal recurrence (IRR) in renal cancer patients after radical nephrectomy (RN) is a rare event and poses a therapeutic dilemma. We evaluated oncologic outcomes in surgically treated patients with IRR and established prognostic factors associated with survival. The benefit of metastasis-directed therapy (MDT) in those with clinical progression after extirpation of IRR was assessed. This was a retrospective single-institutional study in which 60 renal cancer patients after previous RN underwent surgery for suspicion of IRR within the period of 2004-2019; in 55 of them, RCC recurrence was histologically confirmed. No patient had distant metastatic disease at the time of IRR diagnosis. In cases of clinical progression after IRR surgery, MDT (metastasectomy, stereotactic radiotherapy) was selectively used. Kaplan-Meier curves were used to estimate survival outcomes. Univariable and multivariable Cox proportional hazards regression analyses were used to evaluate associations between clinicopathological parameters and cancer-specific survival. Median age at IRR diagnosis was 64 years (range 23-81). IRR was diagnosed at a median of 42 months (IQR 19-99) after RN. Surgical complications of grade 3-5 after IRR extirpation were rare (7%). Median follow-up time was 50 months (IQR 19-80). Five-year recurrence-free survival and cancer-specific survival rates were 32% and 66%, respectively. Radiographic progression was observed in 34 (62%) patients at a median of 11 months after IRR surgery, out of which 22 patients (40%) underwent MDT. When compared with 12 patients without MDT, the MDT patients had a prolonged median time to systemic treatment of 58 (vs. 16 months), and median cancer-specific survival of 88 (vs. 46 months). Upon multivariable analysis, the interval from nephrectomy ≤12 months (HR 7.77), tumour grade 3-4 (HR 13.24) and female sex (HR 7.42) were determined to be independent prognostic factors of cancer-related mortality. Aggressive surgical therapy of IRR is feasible with relatively low morbidity. More than half of the patients experience long-term survival. The interval from nephrectomy to IRR less than 12 months, tumour grade 3-4 and female sex were negative prognostic predictors. In the case of progression, metastasis-directed therapy may prolong the interval to initiation of systemic treatment.

Prognostic value of derived neutrophil-to-lymphocyte ratio (dNLR) in patients with non-small cell lung cancer receiving immune checkpoint inhibitors: a meta-analysis

ObjectivesDerived neutrophil-to-lymphocytes ratio (dNLR) has recently been reported as a novel potential biomarker associated with prognosis of non-small cell lung cancer (NSCLC). However, evidence for the prognostic utility of dNLR...

Delayed Reward Discounting as a Prognostic Factor for Smoking Cessation Treatment Outcome: A Systematic Review

Abstract Introduction While large proportions of smokers attempt to quit, rates of relapse remain high and identification of valid prognostic markers is of high priority. Delayed reward discounting (DRD) is a behavioral economic index of impulsivity that has been associated with smoking cessation, albeit inconsistently. This systematic review sought to synthesize the empirical findings on DRD as a predictor of smoking cessation treatment outcome, to critically appraise the quality of the literature, and to propose directions for future research. Aims and Methods A total of 734 articles were identified, yielding k = 14 studies that met the eligibility criteria. The Quality in Prognosis Studies (QUIPS) tool was used to assess methodological quality of the included studies. Results Individual study methods were highly heterogeneous, including substantial variation in research design, DRD task, clinical subpopulation, and treatment format. The predominant finding was that steeper DRD (higher impulsivity) was associated with significantly worse smoking cessation outcomes (10/14 studies). Negative results tended to be in pregnant and adolescent subpopulations. The QUIPS results suggested low risk of bias across studies; 11/14 studies were rated as low risk of bias for 5/6 QUIPS domains. Conclusions This review revealed consistent low-bias evidence for impulsive DRD as a negative prognostic predictor of smoking cessation treatment outcome in adults. However, methodological heterogeneity was high, precluding meta-analysis and formal tests of small study bias. The prospects of targeting impulsive DRD as a potentially modifiable risk factor or providing targeted treatment for smokers exhibiting high levels of discounting are discussed. Implications These findings indicate consistent evidence for DRD as a negative prognostic factor for smoking cessation outcome in adults. As such, DRD may be a useful as a novel treatment target or for identifying high-risk populations requiring more intensive treatment.

SECISBP2 is a novel prognostic predictor that regulates selenoproteins in diffuse large B-cell lymphoma

AbstractThe overexpression of glutathione peroxidase 4 (GPX4; an enzyme that suppresses peroxidation of membrane phospholipids) is considered a poor prognostic predictor of diffuse large B-cell lymphoma (DLBCL). However, the mechanisms employed in GPX4 overexpression remain unknown. GPX4 is translated as a complete protein upon the binding of SECISBP2 to the selenocysteine insertion sequence (SECIS) on the 3′UTR of GPX4 mRNA. In this study, we investigated the expression of SECISBP2 and its subsequent regulation of GPX4 and TXNRD1 in DLBCL patients. Moreover, we determined the significance of the expression of these selenoproteins in vitro using MD901 and Raji cells. SECISBP2 was positive in 45.5% (75/165 cases) of DLBCL samples. The SECISBP2-positive group was associated with low overall survival (OS) as compared to the SECISBP2-negative group (P = 0.006). Similarly, the SECISBP2 and GPX4 or TXNRD1 double-positive groups (P < 0.001), as well as the SECISBP2, GPX4, and TXNRD1 triple-positive group correlated with poor OS (P = 0.001), suggesting that SECISBP2 may serve as an independent prognostic predictor for DLBCL (hazard ratio (HR): 2.693, P = 0.008). In addition, western blotting showed a decrease in GPX4 and TXNRD1 levels in SECISBP2-knockout (KO) MD901 and Raji cells. Oxidative stress increased the accumulation of reactive oxygen species in SECISBP2-KO cells (MD901; P < 0.001, Raji; P = 0.020), and reduced cell proliferation (MD901; P = 0.001, Raji; P = 0.030), suggesting that SECISBP2-KO suppressed resistance to oxidative stress. Doxorubicin treatment increased the rate of cell death in SECISBP2-KO cells (MD901; P < 0.001, Raji; P = 0.048). Removal of oxidative stress inhibited the altered cell death rate. Taken together, our results suggest that SECISBP2 may be a novel therapeutic target in DLBCL.SECISBP2 overexpression is an independent negative prognostic predictor in diffuse large B-cell lymphoma. Additionally, SECISBP2 positively correlates with selenoprotein expression. In vitro, SECISBP2 knockout increases intracellular reactive oxygen species accumulation via the downregulation of selenoproteins, inhibiting cell growth and promoting cell death after doxorubicin treatment. Therefore, SECISBP2 is a potential therapeutic target for malignant lymphoma.

Low Skeletal Muscle Mass Is a Risk Factor for Aspiration Pneumonia During Chemoradiotherapy.

This study aimed to investigate whether pretreatment skeletal muscle mass index (SMI) is a predictor for the risk of aspiration pneumonia and to explore the relationship between low SMI and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) receiving chemoradiotherapy (CRT). We retrospectively reviewed the data of patients with HNSCC who received CRT during 2010-2019. Patients received a combination of radiotherapy and cisplatin-based chemotherapy (3 cycles of 80 mg/m2 cisplatin on days 1, 22, and 43). Aspiration pneumonia were defined as the presence of both subjective and objective symptoms. Kaplan-Meier curves were generated to analyze survival. Among the 159 patients, 36 (22.6%) developed aspiration pneumonia during treatment. Median SMI in patients with and without pneumonia was 12.4 cm2 /m2 (9.0-20.7) and 13.6 cm2 /m2 (8.1-19.7), respectively (P < .01). Multivariate logistic regression revealed that SMI was the only independent predictor of aspiration pneumonia (P = .0026). Mean OS was significantly shorter for patients with low SMI than for patients with normal SMI (66.9 months vs. 92.7 months, P = .001). Pretreatment low SMI predicts development of aspiration pneumonia and is a strong negative prognostic predictor for OS in patients with HNSCC undergoing CRT. Supportive treatment can be provided to patients at high risk of a low SMI. This study is the first to report SMI as a prognostic predictor in HNSCC. Laryngoscope, 131:E1524-E1529, 2021.

Clinical and radiological mid- to long-term results after direct fixation of posterior malleolar fractures through a posterolateral approach.

Direct fixation of posterior malleolar fractures has been shown to lead to higher accuracy of fracture reduction compared to an indirect anterior to posterior fixation but lacks long-term clinical results. This study shows the mid- to long-term clinical and radiological outcome after direct fixation of the posterior malleolus through a posterolateral approach. Thirty-six patients with an ankle fracture including a posterior malleolar fragment (23 × AO-44C, 12 × AO-44B, 1 × unclassifiable) treated with direct fixation of the fragment through a posterolateral approach were retrospectively evaluated. There were 24 females (67%) with a mean age of 63 (range 34-80) years and a BMI of 28 (range 19-41) kg/m2 at the time of surgery. An initial fracture-dislocation was seen in 67%. The clinical outcome was assessed with the Visual Analog Scale (VAS, 0-10 points) and the American Foot and Ankle Society (AOFAS, 0-100 points) score. Posttraumatic osteoarthritis was recorded with the Van Dijk Classification (grade 0-III). Subgroup analyses of patient- and fracture-associated risk factors (age, BMI, smoking, fracture-dislocation, postoperative articular step-off) were assessed to reveal possible negative prognostic predictors. After a mean follow-up of 7.9 (range 3-12) years, the median VAS was 1 (IQR 0-2) point, and the median AOFAS score was 96 (IQR 88-100) points. Ankle range of motion measurements showed a significant, but clinically irrelevant, difference in plantar- and dorsiflexion between the affected and unaffected ankle. 92% of the patients were very satisfied or satisfied with the postoperative course. 89% had no preoperative signs of ankle osteoarthritis. Osteoarthritis progression was seen in 72%, with 50% showing grade II or III osteoarthritis at the final follow-up. No significant negative prognostic factors for a worse clinical outcome could be detected. Direct fixation of posterior malleolar fractures through a posterolateral approach showed good clinical mid- to long-term results with a high satisfaction rate but substantial development of posttraumatic ankle osteoarthritis. Further studies should include CT analysis of the preoperative fracture morphology and even, perhaps, the postoperative reduction accuracy to evaluate the benefit of posterior malleolar fracture reduction in preventing ankle osteoarthritis in the long term. Therapeutic Level IV. See Instructions for authors for a complete description of levels of evidence.

STK11 Gene Mutation is a Negative Prognostic Predictor for Metastatic Cancer Patients Treated with Immune Checkpoint Inhibitors

STK11 Gene Mutation is a Negative Prognostic Predictor for Metastatic Cancer Patients Treated with Immune Checkpoint Inhibitors

CSF and other interventions

The present talk reviews newer studies with a focus on CSF management in intraventricular hemorrhage and some selected non-surgical interventions in ICH. Intraventricular hemorrhage is a well-established negative prognostic predictor in ICH and different treatment approaches for this condition have been investigated in the recent years. Intraventricular fibrinolysis has been tested in the CLEAR III trial and showed reduced mortality, however no significant difference in clinical outcome as compared to placebo. A subgroup of patients in CLEAR III, namely those with higher IVH volume who were treated until better IVH removal was achieved (>80% of initial volume), benefited from intraventricular tpA. Although IVH removal can be achieved faster with intraventricular fibrinolysis, blood breakdown products still lead to permanent aresorptive hydrocephalus in approximately 15–30% of patients. A recent study (LUCAS-IVH) has investigated a combined approach of intraventricular fibrinolysis and lumbar drainage of CSF after severe IVH, as compared to intraventricular fibrinolysis alone. Lumbar drainage was applied after re-opening of the third and fourth ventricle and led to significantly less shunt surgery. Faster removal of blood degradation products may play a role as a possible mechanism of action in this treatment approach. The only acute treatment in intracerebral hemorrhage that has recently changed based on new results from clinical trials is blood pressure management. After the INTERACT 2 trial showed benefit from intensive BP control, treatment guidelines were adapted. The later published ATACH trial showed no benefit from intensive BP control (110–139 mmHg) as compared to standard treatment (140–179 mmHg systolic BP). Recent subanalyses show that reduction of ICH growth achieved by intensive BP control is somewhat offset by cardio-renal complications. The TICH 2 trial compared treatment with tranexamic acid against placebo in patients with acute ICH within 8h from symptom onset and could not show a significant benefit in clinical outcome. Although there was significantly less ICH growth in the verum group, the absolute difference was small (appr. 1.2 ml less on average). Perihemorrhagic edema is increasingly being recognized as a treatment target after ICH. Non-surgical treatment strategies used in the clinical routine like mannitol and hypertonic saline are presently not based on robust evidence from clinical trials. Deferoxamine did not show promising results in the recently published i-DEF phase II trial. Data on antiinflammatory treatment approaches are still lacking. Hypothermia and machine-based targeted temperature management have only been investigated in small trials on severely affected patients.

Lymph node involvement in pancreatic neuroendocrine tumors: significance as a predictor of survival

Abstract Whether regional lymph node involvement exerts significant effect on the prognosis still remains obscure for pancreatic neuroendocrine tumors. To clarify this association and identify predictors for lymph node involvement, we studied the data of patients aged &gt;18 years with regional lymph node involvement histologically confirmed pancreatic neuroendocrine tumors from 2004 to 2014 in the Surveillance, Epidemiology, and End Results database (http://seer.cancer.gov/about). We evaluated Lymph node involvement as a prognostic factor by Cox regression. We reduced 9 variables of demographic and tumor characteristics to 5 potential predictors using least absolute shrinkage and selection operator (LASSO) regression model. We further constructed a lymph node involvement model by logistic regression. The model was verified by the verification set, and the visual expression of the model was realized by a nomogram. A total of 1545 cases of pancreatic neuroendocrine tumors were included in our study. Lymph node positivity was significantly associated with disease-specific survival (P &lt; 0.001). Younger patients (P &lt; 0.05), patients with tumors in the pancreatic head (P &lt; 0.05), patients at high American Joint Committee on Cancer T stage (P &lt; 0.001), and patients of an undifferentiated status (P &lt; 0.05) showed a significantly higher possibility of developing lymph node involvement. The reliability of this model was verified by cross-validation between the training and testing set, and we obtained good discrimination and calibration power. This model also showed great performance in C-index and area under receiver operating characteristic curve. Lymph node positivity was an important negative prognostic predictor for pancreatic neuroendocrine tumor. We developed a lymph node involvement model based on the predictors including age, marital status, primary site, T status, and tumor grade.

Clinical significance of HER2 and EGFR expression in colorectal cancer patients with ovarian metastasis

BackgroundEGFR and HER2 overexpression has been reported to play important roles in colorectal cancer (CRC) development and metastasis. Ovarian metastasis is rare yet is one of the most malignant metastases of CRC, but very few studies have focused on its biological features. This study aimed to investigate the expression of EGFR and HER2 in ovarian metastases of CRC and to reveal their clinical significance.MethodsThe expression of HER2 and EGFR in both primary tumours and ovarian metastases was analysed by immunohistochemistry (IHC) in 31 CRC patients with ovarian metastases as well as in the primary tumours of 26 CRC patients with non-ovarian metastases. The overall survival time was calculated with a Kaplan-Meier survival curve and compared with a log-rank test.ResultsHER2 positivity in primary tumours was significantly higher in patients with ovarian metastases than in those with non-ovarian metastases (54.5% vs. 36.4%, P < 0.05). The EGFR-positive rate in primary lesions was not significantly different between patients with ovarian metastases and those with non-ovarian metastases (63.6% vs. 58.3%, P > 0.05). HER2 expression was not correlated with age, primary tumour site, tumour differentiation, tumour diameter or vascular cancer embolus (P > 0.05). The positive rates of HER2 and EGFR in ovarian metastases were 44.8 and 69.0%, respectively. HER2 expression in ovarian metastases was correlated with peritoneal metastasis and bilateral ovarian metastasis (P < 0.05) but not with age, synchronous or metachronous ovarian metastases and the primary tumour site (P > 0.05). There was no significant correlation between EGFR expression and the clinicopathological features in ovarian metastases (P > 0.05). CRC patients with HER2-positive ovarian metastases showed a shortened overall survival time compared to that of CRC patients with HER2-negative metastases (17.0 ± 5.2 vs. 32.0 ± 8.3 months).ConclusionOur studies revealed that EGFR and HER2 are highly expressed in the primary tumours and metastases of CRC patients with ovarian metastases. HER2 positivity may be a negative prognostic predictor in patients with ovarian metastases.

The non-coding RNA OTUB1-isoform2 promotes ovarian tumour progression and predicts poor prognosis.

Ovarian cancer is the leading malignancy of the female reproductive system and is associated with inconspicuous early invasion and metastasis. We have previously reported that the oncogene OTUB1 plays a crucial role in ovarian cancer progression, but the role of its isoform, the non‐coding RNA OTUB1‐isoform2, in ovarian cancer is still elusive. Here, we reported that OTUB1‐isoform2 expression in ovarian cancer tissues was significantly higher than that in the paired paratumorous tissues (P < .01). The patients with high expression of OTUB1‐isoform2 had larger tumours than those with low expression (P < .05). The high expression of OTUB1‐isoform2 was correlated with the involvement of bilateral ovaries (P < .05), lymph node metastasis (P < .05), vascular invasion (P < .05), greater omentum involvement (P < .01), fallopian tube involvement (P < .05), advanced FIGO stages (P < .01) and recurrence (P < .01). Moreover, OTUB1‐isoform2 served as an independent negative prognostic predictor for disease‐free survival (DFS) and disease‐specific survival (DSS). Overexpression of OTUB1‐isoform2 in the ovarian cancer cells stimulated cell proliferation, migration and invasion both in vitro and in vivo. In summary, our study suggested that OTUB1‐isoform2 is a novel prognostic biomarker with independent oncogenic functions for ovarian cancer.

Impact of chronic kidney disease on mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. A long-term single-center mortality study.

Chronic kidney disease (CKD) is associated with increased risk of mortality. We examined the impact of moderate and severe CKD at presentation on short- and long-term mortality among unselected patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). The study cohort consists of 501 patients (pts), enrolled from October 2005 to December 2012. The median follow-up was 46.52±25.58 months (range 8-99). A severe CKD (estimated Glomerular Filtration Rate [eGFR] <30 mL/min/1.73 m2) was detected in 16 pts (3.19%), a moderate CKD (eGFR 30-59 mL/min/1.73 m2) in 110 (21.96%) and a normal kidney function (eGFR >60 mL/min/1.73 m2) in 375 (74.85%). The crude in-hospital mortality rate resulted significantly higher in pts with severe and moderate CKD compared to pts with normal renal function (50% and 19.08% versus 2.93%, P<0.0001), as well as the long-term mortality rate (57.14% and 46.34% versus 8.77%, P<0.0001). After adjustment for confounding variables, severe and moderate CKD resulted the main independent predictors of in-hospital (odds ratio [OR]=21.815, P<0.0001 for severe CKD and OR= 4.203, P=0.002 for moderate CKD) and long-term (hazard ratio [HR]= 5.272, P=0.001; HR= 1.978, P=0.006) mortality. CKD is a frequent condition in patients with STEMI treated with PPCI and it is associated to an excess of mortality, resulting the main independent negative prognostic predictor.

B lymphoblastic leukemia/lymphoma: new insights into genetics, molecular aberrations, subclassification and targeted therapy.

B lymphoblastic leukemia/lymphoma (B-ALL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mostly occurs in children and adolescents and is regarded as one of top leading causes of death related to malignancies in this population. Despite the majority of patients with B-ALL have fairly good response to conventional chemotherapeutic interventions followed by hematopoietic stem cell transplant for the last decades, a subpopulation of patients show chemo-resistance and a high relapse rate. Adult B-ALL exhibits similar clinical course but worse prognosis in comparison to younger individuals. Ample evidences have shown that the clinical behavior, response rate and clinical outcome of B-ALL rely largely on its genetic and molecular profiles, such as the presence of BCR-ABL1 fusion gene which is an independent negative prognostic predictor. New B-ALL subtypes have been recognized with recurrent genetic abnormalities, including B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21), B-ALL with translocations involving tyrosine kinases or cytokine receptors (“BCR-ABL1-like ALL”). Genome-wide genetic profiling studies on B-ALL have extended our understanding of genomic landscape of B-ALL, and genetic mutations involved in various key pathways have been illustrated. These include CRLF2 and PAX5 alterations, TP53, CREBBP and ERG mutations, characteristic genetic aberrations in BCR-ABL1-like B-ALL and others. The review further provides new insights into clinical implication of the genetic aberrations in regard to targeted therapy development.