A High Neutrophil-to-Lymphocyte Ratio Predicts Higher Risk of Poststroke Cognitive Impairment: Development and Validation of a Clinical Prediction Model

ObjectivePoststroke cognitive impairment (PSCI) is a serious complication of stroke. The neutrophil-to-lymphocyte ratio (NLR) is a marker of peripheral inflammation. The relationship between the NLR and PSCI is far from well studied, and the thesis of this study was to assess the predictive value of the NLR in patients with PSCI, and establish and verify the corresponding prediction model based on this relationship.MethodsA total of 367 stroke patients were included in this study. Neutrophils, lymphocytes, and NLRs were measured at baseline, and clinical and neuropsychological assessments were conducted 3 months after stroke. The National Institutes of Health Scale (NIHSS) was used to assess the severity of stroke. A Chinese version of the Mini Mental State Examination (MMSE) was used for the assessment of cognitive function.ResultsAfter three months of follow-up, 87 (23.7%) patients were diagnosed with PSCI. The NLR was significantly higher in PSCI patients than in non-PSCI patients (P < 0.001). Patient age, sex, body mass index, NIHSS scores, and high-density lipoprotein levels also differed in the univariate analysis. In the logistic regression analysis, the NLR was an independent risk factor associated with the patients with PSCI after adjustment for potential confounders (OR = 1.67, 95%CI: 1.21–2.29, P = 0.002). The nomogram based on patient sex, age, NIHSS score, and NLR had good predictive power with an AUC of 0.807. In the validation group, the AUC was 0.816.ConclusionAn increased NLR at admission is associated with PSCI, and the model built with NLR as one of the predictors can increase prognostic information for the early detection of PSCI.

Sarcopenia assessed by 4-step EWGSOP2 in elderly hemodialysis patients: Feasibility and limitations

Background In 2019, EWGSOP2 proposed 4 steps to diagnose and assess sarcopenia. We aimed to quantify the prevalence of sarcopenia according to the EWGSOP2 diagnostic algorithm and to assess its applicability in elderly patients on hemodialysis. Methods Prospective study of 60 outpatients on chronic hemodialysis aged 75- to 95-years, sarcopenia was assessed according to the 4-step EWGSOP2: Find: Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls (SARC-F); Assess: grip strength by dynamometry (GSD) and sit to stand to sit 5 (STS5); Confirm: appendicular skeletal muscle mass (ASM) by bioimpedance; Severity: gait speed (GS), Timed-Up and Go (TUG), and Short Physical Performance Battery (SPPB). Results The sequential four steps resulted in a prevalence of confirmed or severe sarcopenia of 20%. Most (97%) patients fulfilled at least one criterion for probable sarcopenia. The sensitivity of SARC-F for confirmed sarcopenia was low (46%). Skipping the SARC-F step increased the prevalence of confirmed and severe sarcopenia to 40% and 37%, respectively. However, 78% of all patients had evidence of dynapenia consistent with severe sarcopenia. Muscle mass (ASM) was normal in 60% of patients, while only 25% had normal muscle strength values (GSD). Conclusions According to the 4-step EWGSOP2, the prevalence of confirmed or severe sarcopenia was low in elderly hemodialysis patients. The diagnosis of confirmed sarcopenia underestimated the prevalence of dynapenia consistent with severe sarcopenia. Future studies should address whether a 2-step EWGSOP2 assessment (Assess-Severity) is simpler to apply and may provide better prognostic information than 4-step EWGSOP2 in elderly persons on hemodialysis.

Utilizing the MEST score for prognostic staging in IgA nephropathy

Background The Oxford classification/MEST score is an established histopathologic scoring system for patients with IgA nephropathy (IgAN). The objective of this study was to derive a prognostic model for IgAN based on the MEST score and histopathologic features. Methods A total of 306 patients with biopsy-proven primary IgAN were included. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford classification. The study endpoint was end-stage renal disease (ESRD). Patients were subclassified into three risk models based on histologic features (Model A), a composite score calculated from the adjusted hazard ratio values (Model B), and on quartiles (Model C). Results The mean follow-up time was 16.5 years (range 0.2–28.1). In total, 61 (20%) patients reached ESRD during the study period. Univariate analysis of M, E, S, T and C lesions demonstrated that all types were associated with an increased risk of ESRD; however, a multivariate analysis revealed that only S, T and C lesions were associated with poor outcomes. Statistical analysis of 15-year data demonstrated that Models A and B were as predictive as the MEST score, with an area-under-the-curve at 0.85. The Harrel c index values were 0.81 and 0.80 for the MEST score and Models A and B, respectively. In the present cohort, adding C lesions to the MEST score did not improve the models prognostic value. Conclusions Patients can be divided into risk classes based on their MEST scores. Histopathologic data provide valuable prognostic information at the time of diagnosis. Model B was the most suitable for clinical practice because it was the most user-friendly.

Congress of Neurological Surgeons Systematic Review and Evidence-based Guidelines Update on the Role of Neuropathology in the Management of Progressive Glioblastoma in Adults

Target population These recommendations apply to adult patients with progressive or recurrent glioblastoma (GBM).QuestionFor adult patients with progressive glioblastoma does testing for Isocitrate Dehydrogenase (IDH) 1 or 2 mutations provide new additional management or prognostic information beyond that derived from the tumor at initial presentation?RecommendationLevel III: Repeat IDH mutation testing is not necessary if the tumor is histologically similar to the primary tumor and the patient’s clinical course is as expected. Question For adult patients with progressive glioblastoma does repeat testing for MGMT promoter methylation provide new or additional management or prognostic information beyond that derived from the tumor at initial presentation and what methods of detection are optimal?Recommendation Level III: Repeat MGMT promoter methylation is not recommended. Question For adult patients with progressive glioblastoma does EGFR amplification or mutation testing provide management or prognostic information beyond that provided by histologic analysis and if performed on previous tissue samples, does it need to be repeated?RecommendationLevel III: In cases that are difficult to classify as glioblastoma on histologic features EGFR amplification testing may help in classification. If a previous EGFR amplification was detected, repeat testing is not necessary. Repeat EGFR amplification or mutational testing may be recommended in patients in which target therapy is being considered.Question For adult patients with progressive glioblastoma does whole genome or large panel sequencing provide management or prognostic information beyond that derived from histologic analysis?RecommendationLevel III: Primary or repeat whole genome or large panel sequencing may be considered in patients who are eligible or interested in molecularly guided therapy or clinical trials.QuestionFor adult patients with progressive glioblastoma should immune checkpoint biomarker testing be performed to provide management and prognostic information beyond that obtained from histologic analysis?RecommendationLevel III: The current evidence does not support making PD-L1 or mismatch repair (MMR) enzyme activity a component of standard testing.QuestionFor adult patients with progressive glioblastoma are there meaningful biomarkers for bevacizumab responsiveness and does their assessment provide additional information for tumor management and prognosis beyond that learned by standard histologic analysis?RecommendationLevel III: No established Bevacizumab biomarkers are currently available based upon the inclusion criteria of this guideline.

The Clinical Impact of Neoadjuvant Endocrine Treatment On Luminal-Like Breast Cancers and Its Prognostic Significance: Results From a Single-institution Prospective Cohort Study

Purpose: Neoadjuvant endocrine treatment (NET) has become a useful tool for the downstaging of luminal-like breast cancers in postmenopausal patients. It enables us to increase breast conserving surgery (BCS) rates, and provides an opportunity for assessing in vivo NET effectiveness and studying any biological changes that may act as valid biomarkers. The purpose of this study was to evaluate the safety and effectiveness of NET, and to assess the role of Ki67 proliferation rate changes as an indicator of endocrine responsiveness.Methods: From 2016 to 2020, a single-institution cohort of patients treated with NET and further surgery was evaluated. In patients with Ki67≥10%, a second core biopsy was performed after four weeks. Information regarding histopathological and clinical changes was gathered.Results: A total of 115 estrogen receptor positive (ER+)/HER2 negative patients were included. The median treatment duration was 5.0 months (IQR: 2.0-6.0). Median maximum size in the surgical sample was 40% smaller than pretreatment size measured by ultrasound (p<.0001). Median pretreatment Ki67 expression was 20.0% (IQR: 12.0-30.0), and was reduced to 5.0% (IQR: 1.8-10.0) after four weeks, and to 2.0% (IQR: 1.0-8.0) in the surgical sample (p<.0001). BCS was performed on 98 patients (85.2%). No pathological complete responses were recorded. A larger Ki67 fold-change after four weeks was significantly related to a PEPI score of 0 (p<.002). No differences were observed between luminal A- and B-like tumors with regard to fold-change and PEPI score.Conclusions: In our cohort, NET has proven effective for tumor size and Ki67 downstaging. This results in a higher rate of conservative surgery, aids in therapeutic decision-making, provides prognostic information, and constitutes a safe and well-tolerated approach

Association of myocardial fibrosis detected by late gadolinium-enhanced MRI with clinical outcomes in patients with diabetes: a systematic review and meta-analysis

ObjectiveThis meta-analysis assessed the associations of myocardial fibrosis detected by late gadolinium-enhanced (LGE)-MRI with the risk of major adverse cardiac and cerebrovascular events (MACCEs) and major adverse cardiac events (MACEs) in patients with diabetes.DesignSystematic review and meta-analysis reported in accordance with the guidelines of the Meta-analysis of Observational Studies in Epidemiology statement.Data sourcesWe searched the Medline, Embase and Cochrane by Ovid databases for studies published up to 27 August 2021.Eligibility criteriaProspective or respective cohort studies were included if they reported the HR and 95% CIs for MACCEs/MACEs in patients with either type 1 or 2 diabetes and LGE-MRI-detected myocardial fibrosis compared with patients without LGE-MRI-detected myocardial fibrosis and if the articles were published in the English language.Data extraction and synthesisTwo review authors independently extracted data and assessed the quality of the included studies. Pooled HRs and 95% CIs were analysed using a random effects model. Heterogeneity was assessed using forest plots and I2 statistics.ResultsEight studies with 1121 patients with type 1 or type 2 diabetes were included in this meta-analysis, and the follow-up ranged from 17 to 70 months. The presence of myocardial fibrosis detected by LGE-MRI was associated with an increased risk for MACCEs (HR: 2.58; 95% CI 1.42 to 4.71; p=0.002) and MACEs (HR: 5.28; 95% CI 3.20 to 8.70; p<0.001) in patients with diabetes. Subgroup analysis revealed that ischaemic fibrosis detected by LGE was associated with MACCEs (HR 3.80, 95% CI 2.38 to 6.07; p<0.001) in patients with diabetes.ConclusionsThis study demonstrated that ischaemic myocardial fibrosis detected by LGE-MRI was associated with an increased risk of MACCEs/MACEs in patients with diabetes and may be an imaging biomarker for risk stratification. Whether LGE-MRI provides incremental prognostic information with respect to MACCEs/MACEs over risk stratification by conventional cardiovascular risk factors requires further study.

Non-thyroidal illness syndrome predicts outcome in adult critically ill patients: a systematic review and meta-analysis

We performed a systematic review and meta-analysis to comprehensively determine the prevalence and the prognostic role of nonthyroidal illness syndrome (NTIS) in critically ill patients. We included studies that assessed thyroid function by measuring the serum thyroid hormone level and in-hospital mortality in adult septic patients. Reviews, case reports, editorials, letters, animal studies, duplicate studies, and studies with irrelevant populations and inappropriate controls were excluded. A total of 6869 patients in 25 studies were included. The median prevalence rate of NTIS was 58% (IQR 33.2-63.7). In univariate analysis, triiodothyronine (T3) and free T3 (FT3) levels in non-survivors were relatively lower than that of survivors (8 studies for T3; standardized mean difference (SMD) 1.16; 95% confidence interval (CI), 0.41–1.92; I2 = 97%; P < 0.01). Free thyroxine (FT4) levels in non-survivors were also lower than that of survivors (12 studies; SMD 0.54; 95% CI, 0.31–0.78; I2 = 83%; P < 0.01). There were no statistically significant differences in TSH levels between non-survivors and survivors. NTIS was independently associated with increased risk of mortality in critically ill patients (OR = 2.21, 95% CI 1.64.- 2.97, I2 = 65% p < 0.01) The results favor the concept that decreased thyroid function might be associated with a worse outcome in critically ill patients. Hence, the measurement of TH could provide prognostic information on mortality in adult patients admitted to ICU.

Improvement of optic nerve pial blood supply visualized through indocyanine green videoangiography after resection of a tuberculum sellae meningioma: 2-dimensional operative video

Ischemia of the optic nerve (ON) is an important cause of visual field deficit provoked by tuberculum sellae (TS) meningiomas. Indocyanine green (ICG) videoangiography could provide prognostic information. Moreover, it allows new insight into the pathophysiology of visual disturbance. The authors present the case of a 48-year-old woman with visual field impairment. Magnetic resonance imaging (MRI) depicted a lesion highly suggestive of a TS meningioma. Following microsurgical resection, ICG videoangiography demonstrated improvement of right ON pial blood supply. In this case, there was one lesion causing visual impairment through both direct compression over the left ON and ischemia to the right nerve. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21155

Properties and functions of TP/PD-ECGF — enzyme and angiogenic factor in norm and in neoplastic pathology

Thymidine phosphorylase is a protein which may has a dual action: it is a rate-limiting enzyme in thymidine metabolism and it is similar to the platelet – derived endothelial cell growth factor (PD/ECGF). The enzyme catalyzes the reversible reaction of phosphorolytic cleavage of thymidine to thymine and deoxyribose-1-phosphate. It has been found that TP has higher activity in tumor tissues. Also it is involved in a proliferative process in a wide variety of chronic inflammatory diseases. Increased expression of PD/ECGF in many tumors is associated with aggressive disease and/or poor prognosis. Its known that high TP activity is related to malignant angiogenesis and invasion. On the other hand, TP inhibits a hypoxia induced apoptotic pathway and enhances expression of various inflammatory cytokines and interferons. This apparent role of enzyme in tumor progression has prompted investigation a large number of TP inhibitors for applicability in chemotherapy backbone regimens. The enzymatic activity of PD/ECGF is being able to generate 5-fluorouracile from capecitabine and other precursors. Thus TP is identified as a prime target for developing novel anticancer therapies. The serum TP level in cancer patients provides useful prognostic information regarding both responses to chemotherapy and length of survival and should be used in planning appropriate therapy. TP could be suggested that control of individual enzyme activity in blood serum may be used as informative tool for monitoring of patients and treatment optimization.

The Stroma Liquid Biopsy Panel Contains a Stromal-Epithelial Gene Signature Ratio That Is Associated with the Histologic Tumor-Stroma Ratio and Predicts Survival in Colon Cancer

Liquid biopsy has emerged as a novel approach to tumor characterization, offering advantages in sample accessibility and tissue heterogeneity. However, as mutational analysis predominates, the tumor microenvironment has largely remained unacknowledged in liquid biopsy research. The current work provides an explorative transcriptomic characterization of the Stroma Liquid BiopsyTM (SLB) proteomics panel in colon carcinoma by integrating single-cell and bulk transcriptomics data from publicly available repositories. Expression of SLB genes was significantly enriched in tumors with high histologic stromal content in comparison to tumors with low stromal content (median enrichment score 0.308 vs. 0.222, p = 0.036). In addition, we identified stromal-specific and epithelial-specific expression of the SLB genes, that was subsequently integrated into a gene signature ratio. The stromal-epithelial signature ratio was found to have prognostic significance in a discovery cohort of 359 colon adenocarcinoma patients (OS HR 2.581, 95%CI 1.567–4.251, p < 0.001) and a validation cohort of 229 patients (OS HR 2.590, 95%CI 1.659–4.043, p < 0.001). The framework described here provides transcriptomic evidence for the prognostic significance of the SLB panel constituents in colon carcinoma. Plasma protein levels of the SLB panel may reflect histologic intratumoral stromal content, a poor prognostic tumor characteristic, and hence provide valuable prognostic information in liquid biopsy.