Physiological network approach to prognosis in cirrhosis: A shifting paradigm.

Decompensated liver disease is complicated by multi-organ failure and poor prognosis. The prognosis of patients with liver failure often dictates clinical management. Current prognostic models have focused on biomarkers considered as individual isolated units. Network physiology assesses the interactions among multiple physiological systems in health and disease irrespective of anatomical connectivity and defines the influence or dependence of one organ system on another. Indeed, recent applications of network mapping methods to patient data have shown improved prediction of response to therapy or prognosis in cirrhosis. Initially, different physical markers have been used to assess physiological coupling in cirrhosis including heart rate variability, heart rate turbulence, and skin temperature variability measures. Further, the parenclitic network analysis was recently applied showing that organ systems connectivity is impaired in patients with decompensated cirrhosis and can predict mortality in cirrhosis independent of current prognostic models while also providing valuable insights into the associated pathological pathways. Moreover, network mapping also predicts response to intravenous albumin in patients hospitalized with decompensated cirrhosis. Thus, this review highlights the importance of evaluating decompensated cirrhosis through the network physiologic prism. It emphasizes the limitations of current prognostic models and the values of network physiologic techniques in cirrhosis.

Biomarkers in idiopathic pulmonary fibrosis: Current insight and future direction.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a dismal prognosis. Early diagnosis, accurate prognosis, and personalized therapeutic interventions are essential for improving patient outcomes. Biomarkers, as measurable indicators of biological processes or disease states, hold significant promise in IPF management. In recent years, there has been a growing interest in identifying and validating biomarkers for IPF, encompassing various molecular, imaging, and clinical approaches. This review provides an in-depth examination of the current landscape of IPF biomarker research, highlighting their potential applications in disease diagnosis, prognosis, and treatment response. Additionally, the challenges and future perspectives of biomarker integration into clinical practice for precision medicine in IPF are discussed.

[Systemic therapeutic strategies for hepatocellular carcinoma: current status and prospects].

Hepatocellular carcinoma (HCC) is a common type of poorly prognosticated malignant tumor. Surgical resection is the preferred treatment method for early-stage HCC. However, at the time of the initial diagnosis, fewer than 30% of patients with liver cancer are suitable for radical therapy. Systemic therapy plays an important role in the treatment process of patients with intermediate- to advanced-stage HCC, as it can effectively extend patients' survival time. With an emphasis on the status and role of systemic therapy for comprehensive management of HCC, this article summarizes the latest progress at home and abroad in the past five years, including first-line combined immunotherapy for advanced-stage HCC, second-line therapy selection, perioperative systemic therapy application, and combined therapy of systemic and local. Currently, the treatment model combined with local therapy has already become a new research hotspot in the treatment of advanced-stage HCC. Nevertheless, in the future, individualized and precise systemic therapeutic strategies will need further exploration.

CDKN2A copy number alteration in bladder cancer: Integrative analysis in patient-derived xenografts and cancer patients.

Bladder cancer (BlCa) is an extensively heterogeneous disease that leads to great variability in tumor evolution scenarios and lifelong patient surveillance, emphasizing the need for modern, minimally invasive precision medicine. Here, we explored the clinical significance of copy number alterations (CNAs) in BlCa. CNA profiling was performed in 15 patient-derived xenografts (PDXs) and validated in The Cancer Genome Atlas BlCa (TCGA-BLCA; n = 408) and Lindgren et al. (n = 143) cohorts. CDKN2A copy number loss was identified as the most frequent CNA in bladder tumors, associated with reduced CDKN2A expression, tumors of a papillary phenotype, and prolonged PDX survival. The study's screening cohort consisted of 243 BlCa patients, and CDKN2A copy number was assessed in genomic DNA and cell-free DNA (cfDNA) from 217 tumors and 189 pre-treatment serum samples, respectively. CDKN2A copy number loss was correlated with superior disease-free and progression-free survival of non-muscle-invasive BlCa (NMIBC) patients. Moreover, a higher CDKN2A index (CDKN2A/LEP ratio) in pre-treatment cfDNA was associated with advanced tumor stage and grade and short-term NMIBC progression to invasive disease, while multivariate models fitted for CDKN2A index in pre-treatment cfDNA offered superior risk stratification of T1/high-grade and EORTC high-risk patients, enhancing prediction of treatment outcome. CDKN2A copy number status could serve as a minimally invasive tool to improve risk stratification and support personalized prognosis in BlCa.

Values of a novel comprehensive prognostic nutritional index (FIDA) in the prognosis of non-small cell lung cancer.

Background: This study focuses on determining the prognostic and predictive value of the comprehensive prognostic nutrition index (FIDA) in individuals undergoing treatment for Non-Small-Cell Lung Carcinoma (NSCLC). Methods: This retrospective analysis encompassed 474 of NSCLC patients treated from January 2010 through December 2019. Employing the Lasso-COX regression approach, eight blood parameters were identified as significant prognostic indicators. These parameters contributed to the formulation of the comprehensive prognostic nutrition index FIDA. Utilizing X-tile software, the patient cohort was categorized into either a high or low FIDA group based on an established optimal threshold. The cohort was then randomly segmented into a training set and a validation set using SPSS software. Subsequent steps involved conducting univariate and multivariate regression analyze to develop a prognostic nomogram. The effectiveness of this nomogram was evaluated by calculating the AUC. Results: Analysis of survival curves for both the training and validation sets revealed a poorer prognosis in the high FIDA group compared to the low FIDA group. This trend persisted across various subgroups, including gender, age, and smoking history, with a statistical significance (p<0.05). Time-dependent ROC and diagnostic ROC analyses affirmed that FIDA serves as an effective diagnostic and prognostic marker in NSCLC. Moreover, Cox regression multivariate analysis established FIDA as an independent prognostic factor for NSCLC. The prognostic nomogram, integrating FIDA and clinical data, demonstrated substantial prognostic utility and outperformed the traditional TNM staging systemin predicting overall survival (OS). Conclusion: FIDA emerges as a dependable predictor of outcomes for patients with NSCLC. It offers a practical, cost-effective tool for prognostication in regular clinical applications.

Treatment, Education, and Prognosis of Slow Learners (Borderline Intelligence).

Objectives: Borderline intelligence has been excluded from formal diagnostic systems and not included in disability diagnoses, leaving gaps in treatment, education, and social welfare despite various functional impairments. Therefore, we aimed to shed light on ways to enhance the intelligence and functioning of individuals with borderline intelligence by reviewing research on its progression, education, and treatment. Methods: Ten studies that met the inclusion and exclusion criteria were included in the final literature review and analyzed according to detailed topics (participant characteristics, design, and results). Results: Borderline intelligence is associated with various comorbid conditions, such as anxiety, depression, attention deficit/hyperactivity disorder, and addictive disorders, which negatively impact its course and prognosis. Individuals with borderline intelligence often face challenges in academics, employment, interpersonal relationships, and health owing to lifelong cognitive impairments. The treatment of borderline intelligence necessitates addressing environmental factors, such as neglect and abuse, as well as treating comorbid mental disorders, which are crucial for prognosis. Tailoring treatment programs for cognitive profile characteristics have been proposed, and studies have reported the effectiveness of pharmacotherapy, working memory training, and intensive rehabilitation training. Therefore, early intervention during childhood brain development is necessary. Risk factors, such as lack of parental education, and their impact on treatment outcomes have also been reported. Conclusion: Extensive research is needed on education, treatment, and prognosis related to borderline intelligence. Active intervention for children with borderline intelligence is essential to improve their functioning and quality of life.

Relationship between recurrence and age in the diffuse sclerosing variant of papillary thyroid carcinoma: clinical significance in pediatric patients.

Background: The diffuse sclerosing variant (DSV) is among the aggressive variants of papillary thyroid carcinoma (PTC) and is more prevalent in pediatric patients than in adult patients. Few studies have assessed its characteristics owing to its low incidence. We aimed to evaluate the relationship between recurrence and age in the DSV of PTC. Methods: We retrospectively reviewed patients diagnosed with the DSV or conventional PTC (cPTC) after surgery at a medical center between May 1988 and January 2019. We compared the clinico-pathological characteristics and surgical outcomes of the DSV and cPTC groups and between adult and pediatric patients with DSV. Results: Among the 24,626 patients, 202 had the DSV, and 24,424 were diagnosed with cPTC. The recurrence rate was significantly higher in the DSV group than in the cPTC group. In the DSV group, the recurrence rate was significantly higher in the pediatric patient group than in the adult patient group. Moreover, the association between recurrence and age group showed different patterns between the DSV and cPTC groups with restricted cubic splines (RCS). While both RCS curves showed a U-shaped distribution, the RCS curve tended to be located within the younger age group. Conclusions: This study demonstrated that pediatric patients with DSV are at a greater risk for recurrence compared with adult patients; moreover, the pattern of recurrence risk according to age is different from that of cPTC.

Adrenalectomy for primary aldosteronism and its related surgical characteristics.

Primary aldosteronism (PA) is a common cause of secondary hypertension. Adrenalectomy is an effective treatment for unilateral PA, particularly aldosterone-producing adenoma (APA), resulting in improvements in biochemical parameters and blood pressure in the vast majority of patients. The article provides a comprehensive overview of PA, focusing on the outcomes of adrenalectomy for PA and the factors that may suggest prognostic implications. Analysis of the outcome of different PA patients undergoing adrenalectomy in terms of preoperative factors, vascular and adipose conditions, type of pathology, and somatic variants. In addition, it is recommended to use the histopathology of primary aldosteronism (HISTALDO) consensus to classify the patient's pathological type, with classical and nonclassical pathological types showing a different prognosis and possibly being associated with an unresected contralateral adrenal gland. The primary aldosteronism surgical outcome (PASO) consensus sets uniform standards for postoperative outcomes in unilateral PA, but its setting of thresholds remains controversial. Partial adrenalectomy shows similar surgical results and fewer postoperative complications than total adrenalectomy, but there is a risk of missing the true source of abnormal aldosterone secretion. Steroid profiling and functional imaging techniques offer alternative options to adrenal vein sampling (AVS) for unilateral and bilateral judgments in patients with PA. A combination of factors is needed to predict the prognosis of PA patients undergoing adrenalectomy in order to manage patient expectations of the outcome of the procedure and to closely monitor blood pressure and biochemical parameters in patients who suggest a poorer prognosis.

Prognostic Impact of Atrial Fibrillation Pattern and other Clinical Biomarkers in Patients with Stroke Admitted in a Tertiary Hospital in Cebu City from 2015-2022.

Background: The effect of atrial fibrillation (AF) patterns and clinical biomarkers among patients with AF-related stroke is still controversial. Objectives: The objective of this study is to determine the association of the pattern of AF and markers on routine blood tests with the outcome of patients after an AF-related stroke. Methods: This is a retrospective cohort study of patients with stroke and AF admitted in a tertiary hospital in Cebu City from 2015-2022. Patients' baseline characteristics, laboratory tests, ECG, and radiologic data were collected. Descriptive statistics such as mean and frequency were computed. The Kaplan-Meier method and the log-rank test were used to calculate the incidence time. The Cox regression analysis was used to determine factors associated with survival. A stepwise regression technique was used in model building. Results: The mortality rate of patients with AF-related stroke was 0.02. A Kaplan Meier survival estimate shows that patients with paroxysmal AF have better survival. Upon model building of variables, age, red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), platelet count, low density lipid cholesterol (LDL-C), and pattern of AF were predictive of mortality in patients with AF-related stroke. Conclusions: Among AF-related stroke patients admitted at a tertiary hospital in Cebu City, pattern of AF, age, RDW, NLR, platelet count, and LDL-C were associated with mortality. The parameters associated with increased mortality could be easily assessed using an ECG, CBC, and lipid profile. These are all readily available and cost-efficient.

Feasibility and Comparative Prognosis of Segmentectomy vs. Lobectomy in Centrally Located Small and Solid Dominant cN0 Non-Small Cell Lung Cancer.

OBJECTIVES: This study aimed to determine the feasibility of segmentectomy in patients with central, whole tumor size ≤2 cm and radiologically solid-dominant cN0 non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 1240 patients who underwent lobectomy or segmentectomy for small and radiologically solid-dominant cN0 NSCLC between January 2010 and December 2022. The inclusion criteria encompassed centrally located tumors defined as tumors located in the inner two-thirds of the pulmonary parenchyma. Propensity score matching was applied to balance the baseline characteristics. RESULTS: Among the 299 eligible patients, no significant differences in recurrence-free survival (RFS) and overall survival (OS) were observed between the segmentectomy (n = 121) and lobectomy (n = 178) groups (P = .794 and .577, respectively). After propensity score matching, no significant differences in hilar and mediastinal lymph node upstaging were found among the 93 matched patients (P = 1.00) and locoregional recurrence was comparable between those who underwent segmentectomy (n = 4) and lobectomy (n = 4). RFS and OS did not significantly differ between the two groups (P = .700 and .870, respectively). Propensity score-adjusted multivariable Cox analysis for RFS and OS indicated that segmentectomy was not an independent prognostic factor (RFS: hazard ratio, 0.89; 95% confidence interval, 0.43-1.85; P = .755; OS: hazard ratio, 1.09; 95% confidence interval, 0.38-3.14; P = .860). CONCLUSIONS: Segmentectomy may be a viable treatment option with local control and prognosis comparable to that of lobectomy in appropriately selected patients with central, small (≤2 cm), and radiologically solid-dominant NSCLC.

Prenatal diagnosis in estimating the prognosis of sacrococcygeal teratoma.

: Sacrococcygeal teratoma is a rare congenital malformation, the prognosis depends on factors affecting foetal development. The diagnosis is based on ultrasound examination, especially the evaluation of the detailed morphology of the foetus in the 20th week of pregnancy. Therefore, it is crucial to keep looking for ultrasound markers that would prenatally determine the most accurate prognosis for the foetus. Now, we rely on a small number of studies with a predominance of case reports. We offer a literature review of the essential information concerning sacrococcygeal teratoma diagnostics, therapy, and complications of sacrococcygeal teratomas in connection with prenatal diagnosis. It turns out that in cases with a favourable prognosis according to prenatal ultrasound examination and adequate surgical treatment after childbirth, the prognosis of this congenital malformation is excellent.

Overview of Research Status in Castleman Disease.

Castleman disease (CD) is characterized by the proliferation of lymphoid tissue and encompasses a range of disorders that vary in clinical presentation, histopathological features, and therapeutic approaches. This article presents a comprehensive review of the current state of CD research, emphasizing the etiology, pathogenesis, clinical manifestations, diagnostic criteria, treatment options, and prognostic factors. CD is a relatively rare condition infrequently encountered in clinical practice. Certain subtypes of CD progress rapidly and pose a significant threat to patient health. Consequently, a timely and accurate diagnosis is crucial. This article aimed to equip clinicians and researchers with an updated and detailed understanding of CD, thereby enhancing the management of this complex condition.

Preoperative MRI-based nomogram to predict survival after curative resection in patients with gallbladder cancer: a retrospective multicenter analysis.

PURPOSE: To use preoperative MRI data to construct a nomogram to predict survival in patients who have undergone R0 resection for gallbladder cancer. METHODS: The present retrospective study included 143 patients (M:F, 76:67; 67.15 years) with gallbladder cancer who underwent preoperative MRI and subsequent R0 resection between 2013 and 2021 at two tertiary institutions. Clinical and radiological features were analyzed using univariate and multivariate Cox regression analysis to identify independent prognostic factors. Based on the multivariate analysis, we developed an MRI-based nomogram for determining prognoses after curative resections of gallbladder cancer. We also obtained calibration curves for 1-,3-, and 5-year survival probabilities. RESULTS: The multivariate model consisted of the following independent predictors of poor overall survival (OS), which were used for constructing the nomogram: age (years; hazard ratio [HR] = 1.04; 95% confidence interval [CI], 1.04-1.07; p = 0.033); tumor size (cm; HR = 1.40; 95% CI, 1.09-1.79; p = 0.008); bile duct invasion (HR = 3.54; 95% CI, 1.66-7.58; p = 0.001); regional lymph node metastasis (HR = 2.47; 95% CI, 1.10-5.57; p = 0.029); and hepatic artery invasion (HR = 2.66; 95% CI, 1.04-6.83; p = 0.042). The nomogram showed good probabilities of survival on the calibration curves, and the concordance index of the model for predicting overall survival (OS) was 0.779. CONCLUSION: Preoperative MRI findings could be used to determine the prognosis of gallbladder cancer, and the MRI-based nomogram accurately predicted OS in patients with gallbladder cancer who underwent curative resection.

Deep learning prediction of survival in patients with heart failure using chest radiographs.

Heart failure (HF) is associated with high rates of morbidity and mortality. The value of deep learning survival prediction models using chest radiographs in patients with heart failure is currently unclear. The aim of our study is to develop and validate a deep learning survival prediction model using chest X-ray (DLSPCXR) in patients with HF. The study retrospectively enrolled a cohort of 353 patients with HF who underwent chest X-ray (CXR) at our institution between March 2012 and March 2017. The dataset was randomly divided into training (n = 247) and validation (n = 106) datasets. Univariate and multivariate Cox analysis were conducted on the training dataset to develop clinical and imaging survival prediction models. The DLSPCXR was trained and the selected clinical parameters were incorporated into DLSPCXR to establish a new model called DLSPinteg. Discrimination performance was evaluated using the time-dependent area under the receiver operating characteristic curves (TD AUC) at 1, 3, and 5-years survival. Delong's test was employed for the comparison of differences between two AUCs of different models. The risk-discrimination capability of the optimal model was evaluated by the Kaplan-Meier curve. In multivariable Cox analysis, older age, higher N-terminal pro-B-type natriuretic peptide (NT-ProBNP), systolic pulmonary artery pressure (sPAP) > 50 mmHg, New York Heart Association (NYHA) functional class III-IV and cardiothoracic ratio (CTR) ≥ 0.62 in CXR were independent predictors of poor prognosis in patients with HF. Based on the receiver operating characteristic (ROC) curve analysis, DLSPCXR had better performance at predicting 5-year survival than the imaging Cox model in the validation cohort (AUC: 0.757 vs. 0.561, P = 0.01). DLSPinteg as the optimal model outperforms the clinical Cox model (AUC: 0.826 vs. 0.633, P = 0.03), imaging Cox model (AUC: 0.826 vs. 0.555, P < 0.001), and DLSPCXR (AUC: 0.826 vs. 0.767, P = 0.06). Deep learning models using chest radiographs can predict survival in patients with heart failure with acceptable accuracy.

DNMT3A-R882: a mutation with many paradoxes.

Understanding the underlying mechanism of acute myeloid leukemia (AML) has led to the discovery of novel biomarkers to help predict, treat and monitor leukemia. DNA (cytosine-5)-methyltransferase 3 A (DNMT3A) is considered a prognostic and therapeutic epigenetic target in AML patients with a hotspot mutation of R882. R882 mutation is associated with impaired differentiation of Hematopoietic stem cells in the bone marrow and disease progression. The prevalence of R882 mutation varied in different ethnicities and countries, and similarly, its prognostic impact differed among numerous studies. Nevertheless, the co-occurrence of mutations in R882 with NPM1 and FLT3 has been reported more frequently and is associated with a worse prognosis. These studies also suggest diverse results regarding bone marrow transplantation response as a treatment, while chemoresistance is reached as a conclusive outcome These findings highlight the crucial need for an in-depth discussion on the significance of the R882 mutation in AML patients. Understanding its impact on leukemic transformation, prognosis, and treatment is vital for advancing clinical implications.

Albumin-to-Globulin Ratio Combined with Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor in Multiple Myeloma with Renal Impairment.

Background: The albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) have been recently regarded as promising prognostic factors in various malignancies. The present study investigated the prognostic value of combining the AGR and NLR (ANS) for risk assessments in multiple myeloma (MM) with renal impairment (RI). Methods: From 2011 to 2018, 79 patients with MM and RI were enrolled in this study. Receiver operating curves (ROCs) were constructed to determine optimal AGR and NLR thresholds for predicting overall survival (OS) and progression-free survival (PFS) during follow up. The prognostic values of AGR, NLR, and ANS were evaluated with Cox regression and Kaplan-Meier methods. We also created a predictive nomogram for prognostic evaluations of OS and PFS, and the predictive accuracy was assessed with a concordance index (c-index). Results: The ROC curves analyses showed that the optimal cut-off levels were 2.27 for NLR and 1.57 for AGR. A high NLR and a high ANS were significantly associated with worse OS and PFS. However, a high NLR combined with a low AGR was associated with worse OS. Multivariate analyses demonstrated that both the NLR and ANS were independent predictors for both OS and PFS and that a low AGR was an independent predictor of a reduced OS. The nomogram accurately predicted OS (c-index: 0.785) and PFS (c-index: 0.786) in patients with MM and RI. Conclusion: ANS may serve as a potential prognostic biomarker in patients with MM and RI. The proposed nomograms may facilitate prognostic predictions for patients with MM and RI.

Platelet-to-lymphocyte ratio as a prognostic predictive marker on adults with traumatic brain injury: Systematic review.

Background: The platelet-to-lymphocyte ratio (PLR) has emerged as a prognostic predictive marker in various diseases, but its role in traumatic brain injury (TBI) has not been fully elucidated. This study aims to evaluate the role of PLR as a prognostic predictive marker in adults with TBI. Methods: This systematic review was conducted according to the Preferred Reporting Items in the Systematic Review and Meta-analysis Guidelines 2020. A comprehensive search was performed using PubMed, Google Scholar, Scopus, Crossref, OpenAlex, Semantic Scholar, Library of Congress, and Jisc Library Hub Discover database to identify relevant studies published up to February 2023. Both prospective and retrospective observational studies written in English or Indonesian were included in the study. No restrictions were placed on the year and country of publication and duration of follow-up. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS), and the risk of bias was estimated using the Cochrane Risk of Bias Assessment Tool for Nonrandomized Research (Ro-BANS) tool. A narrative synthesis was also conducted to summarize the findings. Results: We retrieved 1644 references using the search strategy, and 1623 references were excluded based on screening the title and abstract. The full text was retrieved for 20 articles and subjected to the eligibility criteria, of which 16 were excluded from the study. Four papers with a total of 1.467 sample sizes were included in the review. The median of NOS for study quality was 8-9, with the risk of selection bias using the Ro-BANS tool being low in all studies except for the blinding outcome assessments, which are all unclear. The study finding suggests that the PLR has the potential as an independent prognostic predictive marker in adult patients with TBI. In three studies, a high level of admission PLR may independently predict an increasing mortality risk in 30 days and adverse outcomes measured by the Glasgow outcome scale in 6 months following TBI. However, one study shows that PLR may have limited value as a predictor of mortality or favorable neurological outcomes compared to other hematological parameters. Further studies were needed to establish the clinical utility of PLR and fill the present gaps. Conclusion: This systematic review provides evidence supporting the utilization of PLR as a prognostic predictive marker in adult patients with TBI. The PLR can mainly be utilized, especially in rural practice, as PLR is a simple, low-cost, and routinely performed hematological examination.

[Prognostic factors for neonatal mortality at the Souro Sanou University Hospital in Bobo-Dioulasso, Burkina Faso: a cross-sectional study]. / Facteurs pronostiques de la mortalité néonatale au CHU Sourô Sanou de Bobo-Dioulasso, Burkina Faso: une étude transversale.

Introduction: to help reduce neonatal mortality in Burkina Faso, we identified the prognostic factors for neonatal mortality at the Sourô Sanou University Hospital. Methods: we conducted a cross-sectional and analytical study in the neonatal department from July 25, 2019 to June 25, 2020. Patients' medical records, consultation and hospital records were reviewed. Prognostic factors for neonatal mortality were identified using a Cox model. Results: data from 1128 newborn babies were analysed. Neonatal mortality was 29.8%. Most of these deaths (89%) occurred in the early neonatal period. The mean weight of newborns at the admission was 2,285.8 ± 878.7 and 43.6%. They were at a healthy weight. Four out of five newborns had been hospitalized for infection or prematurity. The place of delivery (HR weight <1000g = 5.45[3.81 -7.79]) and the principal diagnosis (HR asphyxiation= 1.64[1.30-2.08]) were prognostic factors for neonatal mortality. Conclusion: improving technical facilities for the etiological investigation of infections and an efficient management of low-weight newborns suffering from respiratory distress would considerably reduce in-hospital neonatal mortality in Bobo-Dioulasso.

NFκB signalling in colorectal cancer: Examining the central dogma of IKKα and IKKß signalling.

The NFκB pathway, known as the central regulator of inflammation, has a well-established role in colorectal cancer (CRC) initiation, progression, and therapy resistance. Due to the pathway's overarching roles in CRC, there have been efforts to characterise NFκB family members and target the pathway for therapeutic intervention. Initial research illustrated that the canonical NFκB pathway, driven by central kinase IKKß, was a promising target for drug intervention. However, dose limiting toxicities and specificity concerns have resulted in failure of IKKß inhibitors in clinical trials. The field has turned to look at targeting the less dominant kinase, IKKα, which along with NFκB inducing kinase (NIK), drives the lesser researched non-canonical NFκB pathway. However prognostic studies of the non-canonical pathway have produced conflicting results. There is emerging evidence that IKKα is involved in other signalling pathways, which lie outside of canonical and non-canonical NFκB signalling. Evidence suggests that some of these alternative pathways involve a truncated form of IKKα, and this may drive poor cancer-specific survival in CRC. This review aims to explore the multiple components of NFκB signalling, highlighting that NIK may be the central kinase for non-canonical NFκB signalling, and that IKKα is involved in novel pathways which promote CRC.

Does the osteonecrotic volume/other factors predict progression to total knee arthroplasty in spontaneous osteonecrosis of the knee? An MRI study.

Background: The aim of this study is to determine whether the volume of the osteonecrotic lesion in spontaneous osteonecrosis of the knee (SONK) or other prognostic factors predict progression to total knee arthroplasty (TKA). The secondary aim is to analyse co-relation of volume of osteonecrotic lesion versus other prognostic factors The authors hypothesize that a greater osteonecrotic volume predicts progression to TKA. Materials and methods: A retrospective study was conducted at a single tertiary hospital. All patients under the care of a single surgeon with magnetic resonance imaging (MRI)-proven SONK were included from the period of January 2011 to January 2018. Survival analysis was conducted to evaluate for progression to TKA based on volume and location of osteonecrotic lesion. Univariate and multivariate analyses were performed to identify potential risk factors for TKA. Results: 42 patients with MRI-proven SONK were evaluated. 9 patients (21.4 %) required TKA. There was no significant association between progression to TKA with volume of the osteonecrotic lesion. Other factors such as age, gender, body mass index, degree of bony edema and cartilage damage, presence of meniscal tear and subchondral fractures and location of osteonecrotic lesion were also not significant. Conclusion: The volume of the osteonecrotic lesion and other evaluated prognostic factors were not predictive of the progression to TKA for patients with SONK.