The relationship between histopathological features, immunosuppression and outcome in patients undergoing native kidney biopsies.

AIMS: To assess retrospectively the association between histopathological lesions on renal biopsy and subsequent impairment of renal function across the spectrum of kidney diseases and to explore the influence of immunosuppressive therapy within the first 6 months after biopsy on this association. METHODS AND RESULTS: Clinical data from 488 adult patients having a renal biopsy reported at a single centre from 2017 to 2019 were obtained during a median follow-up period of 786 days. Seventeen semi-quantitative histology parameters were recorded at the time of biopsy, 14 of which were suitable for assessment of association with loss of eGFR by multivariable Cox regression analysis, measurement of eGFR slope and measurement of eGFR 12 months after biopsy. A widely used histopathological chronicity score was also assessed. Clinical baseline variables including prescription of immunosuppression were recorded. Seven of 14 histology parameters: mesangial matrix expansion, global glomerulosclerosis, tubular atrophy, interstitial fibrosis, arteriolosclerosis, mesangial hypercellularity and acute tubular injury; and the chronicity score, predicted loss of kidney function by all three measures. Prescription of immunosuppression was more likely in patients with active inflammatory pathology and less likely in patients with chronic fibrotic pathology, and was associated with reduced risk of loss of eGFR. CONCLUSIONS: This retrospective study demonstrates the prognostic significance and complex relationship with immunosuppression of routinely reported histopathological variables in patients having native kidney biopsies, across the spectrum of kidney diseases. It provides useful information for renal biopsy prognostication and design of retrospective studies, including machine learning models.

Unraveling the immunogenic cell death pathways in gastric adenocarcinoma: A multi-omics study.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal (GI) system. However, the lack of reliable biomarkers has made its diagnosis, prognosis, and treatment challenging. Immunogenic cell death (ICD) is a type of programmed cell death that is strongly related to the immune system. However, its function in GC requires further investigation. METHOD: We used multi-omics and multi-angle approaches to comprehensively explore the prognostic features of ICD in patients with stomach adenocarcinoma (STAD). At the single-cell level, we screened genes associated with ICD at the transcriptome level, selected prognostic genes related to ICD using weighted gene co-expression network analysis (WGCNA) and machine learning, and constructed a prognostic model. In addition, we constructed nomograms that incorporated pertinent clinical features and provided effective tools for prognostic prediction in clinical settings. We also investigated the sensitivity of the risk subgroups to both immunotherapy and drugs. Finally, in addition to quantitative real-time polymerase chain reaction, immunofluorescence was used to validate the expression of ICD-linked genes. RESULTS: Based on single-cell and transcriptome WGCNA analyses, we identified 34 ICD-related genes, of which 11 were related to prognosis. We established a prognostic model using the least absolute shrinkage and selection operator (LASSO) algorithm and identified dissimilarities in overall survival (OS) and progression-free survival (PFS) in risk subgroups. The nomograms associated with the ICD-related signature (ICDRS) demonstrated a good predictive value for clinical applications. Moreover, we detected changes in the tumor microenvironment (TME), including biological functions, mutation landscapes, and immune cell infiltration, between the high- and low-risk groups. CONCLUSION: We constructed an ICD-related prognostic model that incorporated features related to cell death. This model can serve as a useful tool for predicting the prognosis of GC, targeted prevention, and personalized medicine.

Annual Mammographic Screening Reduces the Risk of Interval or Higher Stage Invasive Breast Cancers Among Postmenopausal Women in the Ontario Breast Screening Program.

Purpose: In the Ontario Breast Screening Program (OBSP) annual screening improved breast cancer detection for women 50-74 years with a family/personal history compared to biennial, while detection was equivalent for women screened annually for mammographic density ≥75%. This study compares the risk of interval or higher stage invasive cancers among postmenopausal women screened annually vs biennially by age and estrogen use. Methods: A retrospective design identified 4247 invasive breast cancers diagnosed among concurrent cohorts of women 50-74 screened in the OBSP with digital mammography between 2011 and 2014, followed until 2016. Polytomous logistic regression estimated the risk of interval or higher stage breast cancers by age and estrogen use between women screened annually because of first-degree relative with breast or ovarian cancer or personal history of ovarian cancer, or mammographic density ≥75%, and those screened biennially. Results: The risk of interval vs screen-detected cancers was significantly reduced in women screened annually for family/personal history (OR=.64; 95%CI:0.51-.80), particularly those 60-74 years (OR=.59; 95%CI:0.45-.77) or not currently using estrogen (OR=.66; 95%CI:0.52-.83) compared to those screened biennially. The risk of stage II-IV vs stage I tumors was also lower in women 60-74 years screened annually for family/personal history (OR=.79; 95%CI:0.64-.97) and in those screened annually for mammographic density ≥75% currently using estrogen (OR=.51; 95%CI:0.26-1.01) compared to women screened biennially. Conclusion: Postmenopausal women at increased risk screened annually had equivalent or reduced risks of interval or higher stage invasive breast cancers than those screened biennially, further supporting risk-based screening in this population.

Breast cancer in women younger than 35 years old.

PURPOSE: Women ≤ 35 years old with breast cancer constitute a special group. Considering the impact of the disease and its prognosis, these patients face some specific problems that are not present in older women. What are the prognostic features of the survival rate in very young women with breast cancer? METHODS: Retrospective analysis of very young women with breast cancer from the Surgical-Oncologic Breast Cancer Department at "Theagenio" Anticancer Hospital, 2003-2016. Patient and tumor characteristics, treatment options and follow-up information were collected. Univariate-multivariate analyses were conducted and survival rates were calculated. RESULTS: The median age was 34 years old. 53 patients (41%) had T1, 36 (28%) had T2, 7 (5.4%) had T3 and 33 (25.6%) had T4 stage tumors. Most women, 114 (88.4%), had ductal carcinoma in their histology. Furthermore, positive axillary lymph nodes were present in 62 women (48%). In the immunochemistry report, 91 patients (70.5%) were hormone receptor positive, HER2 was overexpressed in 32 patients (24.8%) and 27 patients presented with triple-negative subtype. Out of 65 patients tested for Ki-67, 51 (78.5%), had a high expression (cut-off value of 20%). After adjusting for all possible factors, the risk of recurrence and death was six times higher in the positive lymph node group, (p < 0.001). The median disease-free and overall survival was 133 and > 173 months, respectively. CONCLUSION: Breast cancer in very young women appears with large size and high-grade tumors, high incidence of infiltrated axillary lymph nodes, high Ki-67 expression and intrinsic subtypes with poor prognosis. As a result, these women need to be treated by a multidisciplinary team.

Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients.

BACKGROUND/AIMS: Colorectal mucinous adenocarcinoma (MA) has been associated with a worse prognosis than adenocarcinoma (AD) in advanced stages. Little is known about the prognostic impact of a mucinous histotype on the early stages of colorectal cancer with negative lymph node (LN) metastasis. In contrast to the established prognostic factors such as T stage and grading, the histological subtype is not thought to contribute to the therapeutic outcome, although different subtypes can potentially represent different entities. In this study, we aimed to define the prognostic value of mucinous histology in colorectal cancer with negative LNs. METHODS: Between 2006 and 2017, a total of 4893 consecutive patients without LN metastasis underwent radical surgery for primary colorectal cancer (MA and AD) in Fudan University Shanghai Cancer Center (FUSCC). Clinical, histopathological, and survival data were analyzed. RESULTS: The incidence of MA was 11% in 4893 colorectal cancer patients without LN metastasis. The MA patients had a higher T category, a greater percentage of LN harvested, larger tumor size and worse grading than the AD patients (p < 0.001 for each). We found that MA histology was correlated with a poor prognosis in terms of relapse in node-negative patients, and MA histology combined with TNM staging may be a feasible method for predicting the relapse rate. Additionally, MA presented as a high-risk factor in patients with negative perineural or vascular invasion and well/moderate-differentiation and showed a more dismal prognosis for stage II patients. Meanwhile, the disease-free survival was identical in MA and AD patients after neo- and adjuvant chemotherapy. CONCLUSION: MA histology is an independent predictor of poor prognosis due to relapse in LN-negative colorectal cancer patients. Mucinous histology can suggest a possible high risk in early-stage colorectal carcinoma.

Clinical outcomes of radiotherapy for spinal cord ependymoma with adverse prognostic features: a single-center study.

PURPOSE: This study evaluated the outcomes of radiotherapy (RT) for spinal ependymoma with adverse features, such as incomplete resection or disseminated disease. METHODS: Twenty-five patients underwent RT for spinal cord ependymoma during 1991-2016. Twenty-four patients had gross disease on the pre-RT spinal magnetic resonance images. Six patients (24%) had disseminated disease. The World Health Organization grades were I (12 patients), II (12 patients), and III (1 patient). The RT fields were the tumor bed plus margin in 19 patients (76%), the entire craniospinal axis in 5 patients (20%), and the entire spinal canal with posterior cranial fossa in 1 patient (4%). The median RT dose was 50.4 Gy (range 44.0-59.4 Gy). RESULTS: The median follow-up was 49 months (range 9-321 months), with 5-year overall and progression-free survival rates of 83.7% and 70.8%, respectively. Relative to patients with grade II/III ependymoma, patients with grade I ependymoma had higher 5-year rates of overall survival (100% vs. 69.4%, P = .088) and progression-free survival (100% vs. 42.3%, P = .02). Disease progression was observed in 4 patients who had grade II ependymoma, including 2 of 6 patients with disseminated disease and 2 of 19 patients with localized disease. Twelve patients (48%) exhibited improved neurological function. One patient who underwent craniospinal irradiation developed late hypopituitarism. No other RT-related late toxicities were observed. CONCLUSIONS: Favorable survival outcomes were achieved using RT for spinal ependymoma with adverse prognostic features. Thus, RT may be an effective treatment option when complete tumor removal cannot be achieved.

Significance of pleural effusion at diagnosis in pediatric Hodgkin lymphoma: a report from Children's Oncology Group protocol AHOD0031.

BACKGROUND: Pleural effusion at presentation in Hodgkin lymphoma has been associated with inferior outcome but has not been systematically evaluated. OBJECTIVE: To determine whether pleural effusion at presentation in children with Hodgkin lymphoma is a primary indicator of poor prognosis or secondary to associated factors. MATERIALS AND METHODS: Children's Oncology Group (COG) AHOD0031, a randomized, response-based, centrally reviewed protocol, enrolled 1,712 eligible patients <22 years of age with initial presentation of intermediate risk, biopsy-proven Hodgkin lymphoma; 1,423 had available imaging for retrospective review. We coded effusions as fluid-only or with associated pleural nodule or adjacent lung or bone involvement and correlated this with disease stage, tumor response, large mediastinal adenopathy, and mass effect on the superior vena cava (SVC) and left innominate vein. We recorded change in size and character of effusions post-chemotherapy. RESULTS: Pleural effusions were present in 217, with 204 having fluid-only and 13 having associated solid components. Patients with effusions were more likely to have large mediastinal adenopathy (P<0.0001), be slow early responders (P<0.0001) and have higher relapse rate (P<0.0001). Vascular compression was not significantly correlated with pleural effusion. Of 121 patients with adequate [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT imaging, no FDG PET avidity was seen in any pleural effusion but was present in solid components. The side of the pleural effusion in those with moderate or large effusions was highly associated with the side of large mediastinal adenopathy (P<0.0001). Statistical analysis indicates that pleural effusion is an independent risk factor for poorer response and relapse. CONCLUSION: Pleural effusion in Hodgkin lymphoma is an important independent poor prognostic indicator for response and relapse.

Adjuvant chemotherapy use and outcomes of patients with high-risk versus low-risk stage II colon cancer.

BACKGROUND: Adjuvant chemotherapy (AC) is frequently considered in patients with stage II colon cancer who are considered to be at high risk. However, to the authors' knowledge, the survival benefits associated with AC in these patients remain largely unproven. In the current study, the authors sought to examine the use of AC in patients with AJCC stage II colon cancer and to compare the impact of AC on outcomes in patients with high-risk versus low-risk disease in a population-based setting. METHODS: Patients with stage II colon cancer who were evaluated at 1 of 5 regional cancer centers in British Columbia from 1999 to 2008 were analyzed. Kaplan-Meier and Cox regression methods were used to correlate high-risk versus low-risk status and receipt of AC with recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). RESULTS: A total of 1697 patients were identified: 1286 (76%) with high-risk and 411 (24%) with low-risk disease, among whom 373 (29%) and 51 (12%),respectively, received AC. Individuals with high-risk disease treated with AC were younger (median age, 62 years vs 72 years; P<.001) and had better Eastern Cooperative Oncology Group performance status (0/1: 47% vs 33%; P = .001). For high-risk patients, AC was associated with improved OS (hazard ratio [HR], 0.65; 95% confidence interval [95% CI], 0.50-0.83 [P = .001]). However, no significant benefits with regard to RFS or DSS were observed. Subgroup analyses revealed that AC in patients with T4 disease was associated with significantly improved RFS (HR, 0.63; 95% CI, 0.42-0.95 [P = .03]), DSS (HR, 0.59; 95% CI, 0.37-0.93 [P = .02]), and OS (HR, 0.50; 95% CI, 0.33-0.77 [P = .002]). For patients with low-risk disease, AC was associated with inferior RFS (HR, 2.18; 95% CI, 1.00-4.79 [P = .05]) and DSS (HR, 3.01; 95% CI, 1.10-8.23 [P = .03]). CONCLUSIONS: In this population-based analysis, AC was associated with an OS advantage in high-risk patients, most likely due to patient selection. RFS, DSS, and OS benefits were mainly observed in patients with T4 disease, suggesting a limited role for AC in patients deemed to be high risk by non-T4 features.

Machine learning-based prediction of clinical outcomes after traumatic brain injury: Hidden information of early physiological time series.

AIMS: To assess the predictive value of early-stage physiological time-series (PTS) data and non-interrogative electronic health record (EHR) signals, collected within 24 h of ICU admission, for traumatic brain injury (TBI) patient outcomes. METHODS: Using data from TBI patients in the multi-center eICU database, we focused on in-hospital mortality, neurological status based on the Glasgow Coma Score (mGCS) motor subscore at discharge, and prolonged ICU stay (PLOS). Three machine learning (ML) models were developed, utilizing EHR features, PTS signals collected 24 h after ICU admission, and their combination. External validation was performed using the MIMIC III dataset, and interpretability was enhanced using the Shapley Additive Explanations (SHAP) algorithm. RESULTS: The analysis included 1085 TBI patients. Compared to individual models and existing scoring systems, the combination of EHR and PTS features demonstrated comparable or even superior performance in predicting in-hospital mortality (AUROC = 0.878), neurological outcomes (AUROC = 0.877), and PLOS (AUROC = 0.835). The model's performance was validated in the MIMIC III dataset, and SHAP algorithms identified six key intervention points for EHR features related to prognostic outcomes. Moreover, the EHR results (All AUROC >0.8) were translated into online tools for clinical use. CONCLUSION: Our study highlights the importance of early-stage PTS signals in predicting TBI patient outcomes. The integration of interpretable algorithms and simplified prediction tools can support treatment decision-making, contributing to the development of accurate prediction models and timely clinical intervention.

Leveraging FAM features to predict the prognosis of LGG patients and immunotherapy outcome.

Heterogeneity at biological and transcriptomic levels poses a challenge in defining and typing low-grade glioma (LGG), leading to a critical need for specific molecular signatures to enhance diagnosis, therapy, and prognostic evaluation of LGG. This study focused on fatty acid metabolism (FAM) related genes and prognostic features to investigate the mechanisms and treatment strategies for LGG cell metastasis and invasion. By screening 158 FAM-related genes and clustering 512 LGG samples into two subtypes (C1 and C2), differential gene expression analysis and functional enrichment were performed. The immune cell scores and prognosis were compared between the two subtypes, with C1 showing poorer outcomes and higher immune scores. A four-gene signature (PHEX, SHANK2, HOPX, and LGALS1) was identified and validated across different datasets, demonstrating a stable predictive effect. Cellular experiments confirmed the roles of LGALS1 and HOPX in promoting tumor cell proliferation, migration, and invasion, while SHANK2 exhibited a suppressive effect. This four-gene signature based on FAM-related genes offers valuable insights for understanding the pathogenesis and clinical management of LGG.

Identification and clinical validation of diverse cell-death patterns-associated prognostic features among low-grade gliomas.

Low-grade glioma (LGG) is heterogeneous at biological and transcriptomic levels, and it is still controversial for the definition and typing of LGG. Therefore, there is an urgent need for specific and practical molecular signatures for accurate diagnosis, individualized therapy, and prognostic evaluation of LGG. Cell death is essential for maintaining homeostasis, developing and preventing hyperproliferative malignancies. Based on diverse programmed cell death (PCD) related genes and prognostic characteristics of LGG, this study constructed a model to explore the mechanism and treatment strategies for LGG cell metastasis and invasion. We screened 1161 genes associated with PCD and divided 512 LGG samples into C1 and C2 subtypes by consistent cluster analysis. We analyzed the two subtypes' differentially expressed genes (DEGs) and performed functional enrichment analysis. Using R packages such as ESTIMATE, CIBERSOTR, and MCPcounter, we assessed immune cell scores for both subtypes. Compared with C1, the C2 subtype has a poor prognosis and a higher immune score, and patients in the C2 subtype are more strongly associated with tumor progression. LASSO and COX regression analysis screened four characteristic genes (CLU, FHL3, GIMAP2, and HVCN1). Using data sets from different platforms to validate the four-gene feature, we found that the expression and prognostic correlation of the four-gene feature had a high degree of stability, showing stable predictive effects. Besides, we found downregulation of CLU, FHL3, and GIMAP2 significantly impairs the growth, migration, and invasive potential of LGG cells. Take together, the four-gene feature constructed based on PCD-related genes provides valuable information for further study of the pathogenesis and clinical treatment of LGG.

Mu opioid receptor mRNA overexpression predicts poor prognosis among 18 common solid cancers: A pan-cancer analysis.

Background: Opioids are widely used for patients with solid tumors during surgery and for cancer pain relief. We conducted a pan-cancer genomic analysis to investigate the prognostic features of Mu opioid receptor (MOR) mRNA expression across 18 primary solid cancers. Methods: All the data of cancer with MOR mRNA were retrieved from cBioPortal for Cancer Genomics. Logistic regression was used to determine the associations between MOR mRNA expression and clinicopathological features. Log-rank test and Cox regression was used for survival analysis. Subgroup analysis and propensity score matching were also carried out. Results: 7,274 patients, including 1,112 patients with positive MOR mRNA expression, were included for data analyses. Positive MOR mRNA expression was associated with more advanced stage of T (adjusted Odds ratio [OR], 1.176; 95% confidence interval [CI], 1.022-1.354; P=0.024), M (adjusted OR, 1.548; 95% CI, 1.095-2.189; P=0.013) except N (adjusted OR, 1.145; 95% CI, 0.975-1.346; P=0.101), and worse prognosis for overall survival (Hazard ratio [HR] 1.347, 95% CI 1.200-1.512, P<0.001), progression-free survival (HR 1.359, 95% CI 1.220-1.513, P<0.001), disease-free survival (HR 1.269, 95% CI 1.016-1.585, P<0.001) and disease-specific survival (HR 1.474, 95% CI 1.284-1.693, P<0.001). Patients with positive MOR mRNA expression tended to be classified as tumor microenvironment immune types II, representing low PD-L1 and low CD8A expression. Conclusion: MOR mRNA overexpression is associated with poor prognosis and poor response to PD-L1 therapy.

Construction and validation of a prognostic model for predicting clear cell renal cell carcinoma based on complement-related genes.

Background: Clear cell renal cell carcinoma (ccRCC) is a highly heterogeneous tumor and is the most common subtype of renal cell carcinoma (RCC). Surgery is used to cure most early ccRCC, but the 5-year overall survival (OS) of ccRCC patients is far from satisfactory. Thus, new prognostic features and therapeutic targets for ccRCC need to be identified. Since complement factors can influence tumor development, we aimed to develop a model to predict the prognosis of ccRCC through complement-related genes. Methods: Differentially expressed genes were screened from an International Cancer Genome Consortium (ICGC) data set, and the genes associated with prognosis were screened by univariate regression and least absolute shrinkage and selection operator-Cox regression, and column line plots were generated using the rms R package to predict OS. The C-index was used to show the accuracy of the survival prediction and the prediction effects were verified using a data set from The Cancer Genome Atlas (TCGA). An immuno-infiltration analysis was performed with CIBERSORT analysis, and a drug sensitivity analysis was performed using the Gene Set Cancer Analysis (GSCA) (http://bioinfo.life.hust.edu.cn/GSCA/#/) database. Results: We identified 5 complement-related genes (i.e., A2M, APOBEC3G, COL4A2, DOCK4, and NOTCH4) for risk-score modeling to predict OS at 1, 2, 3, and 5 years, and the C-index of the prediction mode was 0.795. In addition, the model was successfully validated in TCGA data set. The CIBERSORT analysis showed that M1 macrophages were downregulated in the high-risk group. The GSCA database analysis showed that DOCK4, COL4A2, and A2M were positively correlated with the half maximal inhibitory concentration (IC50) of 10 drugs and small molecules, and COL4A2, NOTCH4, A2M, and APOBEC3G were negatively correlated with the IC50 of dozens of different drugs and small molecules. Conclusions: We developed and validated a survival prognostic model based on 5 complement-related genes for ccRCC. We also elucidated the relationship with tumor immune status and developed a new predictive tool for clinical purposes. In addition, our results showed that A2M, APOBEC3G, COL4A2, DOCK4, and NOTCH4 may be potential targets for the treatment of ccRCC in the future.

Long-Term Outcome of Differentiated Thyroid Cancer Patients-Fifty Years of Croatian Thyroid Disease Referral Centre Experience.

Background: Indolent nature but a high incidence of differentiated thyroid cancer (DTC) remains a challenge for optimizing patient care. Therefore, prognostic factors present valuable information for determining an adequate clinical approach. Methods: This study assessed prognostic features of 1167 papillary (PTC) and 215 follicular (FTC) thyroid cancer patients that had undergone surgery between 1962 and 2012, and were followed-up up to 50 years in a single institution, till April 2020. Age, gender, tumor size, presence of local and distant metastases at presentation, extrathyroidal extension, disease recurrence, and cancer-specific survival were evaluated. Results: In multivariate analysis, factors affecting the worse outcome were age (p = 0.005), tumor size (p = 0.006), and distant metastases (p = 0.001) in PTC, while extrathyroidal extension (p < 0.001), neck recurrence (p = 0.002), and distant metastases (p < 0.001) in FTC patients. Loco-regional recurrence rate was 6% for PTC and 4.7% for FTC patients, while distant metastases were detected in 4.2% PTC and 14.4% of FTC patients. The 10-year cancer-specific survival rates for PTC and FTC were 98.6% and 89.8%, respectively (p < 0.001). Conclusions: Negative prognostic factors, besides distant metastases, were older age and greater tumor size in PTC, and extrathyroidal extension and neck recurrence in FTC patients. The recurrence and mortality rates were very low.

Contemporary advances in anti-NMDAR antibody (Ab)-mediated encephalitis.

The study of antibody (Ab)-mediated encephalitis has advanced dramatically since the discovery of antibodies directed against the N-methyl-D-aspartate receptor (NMDAR) in association with a unique neuro-psychiatric syndrome, over a decade-and-a-half ago. Anti-NMDAR Ab-mediated encephalitis now represents the most well characterised form of autoimmune encephalitis. The disease most commonly manifests in young women, but all ages and both sexes can be affected. Autoantibodies may arise in the context of two well-recognised disease triggers in a proportion of patients, and ultimately facilitate NMDAR displacement from synapses. Various CSF cytokines, chemokines, and other molecules have been explored as candidate biomarkers but are limited in sensitivity and specificity. The clinical spectrum is diverse, with evolution and a combination of neuro-psychiatric abnormalities at disease nadir common. Anti-NMDAR Ab-mediated encephalitis is immunotherapy responsive, and a near-majority ultimately acquire a broadly favourable clinical outcome. The diagnosis, and more particularly, the management of the disease can still hold considerable challenges. Moreover, well-defined biomarkers remain elusive. The present review will therefore delineate pathogenic and clinical advances to date in anti-NMDAR antibody-mediated encephalitis.

Contemporary advances in antibody-mediated encephalitis: anti-LGI1 and anti-Caspr2 antibody (Ab)-mediated encephalitides.

Encephalitides with antibodies directed against leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (Caspr2) represent two increasingly well characterised forms of autoimmune encephalitis. Both share overlapping and distinct clinical features, are mediated by autoantibodies directed against differing proteins complexed with voltage-gated potassium channels, with unique genetic predisposition identified to date. Herein we summarise disease mechanisms, clinical features, treatment considerations, prognostic factors and clinical outcomes regarding these disorders.

Histology of Colorectal Carcinoma: Proven and Purported Prognostic Factors.

Although tumor stage has a profound influence on prognosis, several histologic features are also important. These parameters predict biological behavior and can be used by clinicians to determine whether patients are at high risk for disease progression and, thus, are candidates for adjuvant therapy, particularly when they have localized (ie, stage II) disease. This article summarizes the evidence supporting the prognostic values of various histologic parameters evaluated by pathologists who assign pathologic stage to colorectal cancers. Criteria to be discussed include histologic subtype, tumor grade, lymphatic and perineural invasion, tumor budding, and host immune responses.

Treatment of Smoldering Multiple Myeloma: Ready for Prime Time?

The current standard of care for smoldering multiple myeloma (SMM) is observation until there is end-organ involvement. With newer and more effective treatments available, a question that is increasingly asked is whether early intervention in patients with SMM will alter the natural history of their disease. Herein, we review the evolving definition of SMM and risk stratification models. We discuss evidence supporting early intervention for SMM-both as a preventative strategy to delay progression and as an intensive treatment strategy with a goal of potential cure. We highlight ongoing trials and focus on better defining who may require early intervention.

Association between the degree of fibrosis in fibrotic focus and the unfavorable clinicopathological prognostic features of breast cancer.

OBJECTIVE: To explore the association between the degree of fibrosis in fibrotic focus (FF) and the unfavorable clinicopathological prognostic features of breast cancer. METHODS: A total of 169 cases of breast invasive ductal carcinoma (IDC) were included in the study. Hematoxylin and eosin (H&E) staining was performed in the primary lesion of breast IDC and the degree of fibrosis in tumor-stromal FF was assessed. The association between the degree of fibrosis in FF and the well-known clinicopathologic features of breast cancer was investigated and the influence of the degree of fibrosis in FF on the survival was analyzed. RESULTS: Tumor size >2 cm (P = 0.023), vascular invasion (P = 0.011), lymphatic vessel invasion (P < 0.001) and HER-2+ (P = 0.032) were positively correlated with the degree of fibrosis in FF in breast IDC. The result of multivariate analysis showed that lymphatic vessel invasion was the only independent correlation factor of high fibrosis in FF in breast IDC (OR = 3.82, 95% CI[1.13 ∼ 12.82], P = 0.031). The Nottingham prognostic index (NPI) of high fibrosis in FF was significantly higher than that of mild and moderate fibrosis in FF in the no vascular infiltration subgroup, the no nerve infiltration subgroup, and the Luminal A subgroup (P = 0.014, 0.039, and 0.018; respectively). CONCLUSIONS: The high fibrosis in FF is closely associated with the strong invasiveness and the high malignancy of breast IDC. The degree of fibrosis in FF might be considered as a very practical and meaningful pathological feature of breast cancer.