Tumor necrosis in magnetic resonance imaging predicts urothelial carcinoma with squamous differentiation in muscle-invasive bladder carcinoma.

PURPOSE: This study investigated radiologic features on preoperative MRI to differentiate urothelial carcinoma with squamous differentiation (UCSD) from conventional urothelial carcinoma (UC) in muscle-invasive bladder carcinoma. METHODS: Ninety-nine patients who underwent radical cystectomy and a preoperative bladder MRI scan within three months before surgery were retrospectively enrolled. Various MRI features, including tumor length, location, multiplicity, long-to-short axis ratio, morphology, radiologic stage, and degree of severe necrosis, were analyzed. Univariable and multivariable logistic regression analyses were performed to identify MRI features predictive of UCSD. The diagnostic performance of a significant MRI feature was assessed using 5-fold cross-validation. RESULTS: Among the MRI features, significant radiologic findings associated with UCSD in the univariable analysis included heterogeneous tumor signal intensity in T2-weighted images (odds ratio [OR], 3.365; 95% confidence interval [CI], 1.213-9.986; P = 0.022) and contrast-enhanced T1-weighted images (OR, 4.428; 95% CI, 1.519-12.730; P = 0.007), as well as marked (≥ 50%) severe necrosis (OR, 17.100; 95% CI, 4.699-73.563; P < 0.001). In the multivariable analysis, marked (≥ 50%) severe necrosis (odds ratio [OR], 13.755; 95% confidence interval [CI], 2.796-89.118; P = 0.004) was a significant predictor of UCSD. Marked (≥ 50%) severe necrosis showed a high specificity of 95.0% with a precision of 65.0% for diagnosing UCSD based on 5-fold cross-validation. CONCLUSION: Preoperative bladder MRI revealing marked severe necrosis may be indicative of UCSD and can assist in distinguishing it from conventional UC.

Modified Thoracoabdominal Nerves Block Through Perichondral Approach: A Systematic Review and Meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to investigate the postoperative analgesic efficacy and safety of the modified thoracoabdominal nerve block through the perichondral approach (M-TAPA) in abdominal surgeries. DESIGN: Systematic review and meta-analysis. METHODS: We searched electronic databases to identify relevant studies comparing M-TAPA with conventional analgesic techniques. The primary outcome was the requirement for rescue analgesia at 12 and 24 hours postsurgery. Secondary outcomes included the 11-point numerical rating scale pain scores at 0, 1, 2, 4, 6, 8, 12, and 24 hours following surgery, global quality of recovery scores, and postoperative adverse events. FINDINGS: Five randomized controlled trials involving 308 patients were analyzed. M-TAPA showed no significant difference in the requirement for rescue analgesia at 12 hours (relative risk [RR]: 0.87; 95% confidence interval [CI]: 0.62, 1.22; P = .424; I2 = 40.7%; Ph = .185) and 24 hours (RR: 0.67; 95% CI: 0.22, 1.99; P = .252; I2 = 90.3%; Ph < .001) postsurgery compared to non-M-TAPA. No significant differences in numerical rating scale pain scores or global quality of recovery scores were found between the two groups (all P < .05). However, M-TAPA was associated with a lower occurrence of nausea (RR: 0.37; 95% CI: 0.22, 0.68; P < .001; I2 = 0%; Ph = .834), vomiting (RR: 0.32; 95% CI: 0.17, 0.62; P < .001; I2 = 0%; Ph = .884), and itching (RR: 0.38; 95% CI: 0.21, 0.70; P = .002; I2 = 0%; Ph = .826). CONCLUSIONS: There was no significant difference in analgesic efficacy and safety between M-TAPA and non-M-TAPA techniques.

Peripheral zone thickness in preoperative MRI is predictive of Trifecta achievement after Holmium laser enucleation of the prostate (HoLEP).

PURPOSE: To investigate various anatomical features of the prostate using preoperative MRI and patients' clinical factors to identify predictors of successful Holmium:YAG laser enucleation of the prostate (HoLEP). METHODS: 71 patients who had received HoLEP and undergone a 3.0-T prostate MRI scan within 6 months before surgery were retrospectively enrolled. MRI features (e.g., total prostate and transitional zone volume, peripheral zone thickness [PZT], BPH patterns, prostatic urethral angle, intravesical prostatic protrusion, etc.) and clinical data (e.g., age, body mass index, surgical technique, etc.) were analyzed using univariable and multivariable logistic regression to identify predictors of successful HoLEP. Successful HoLEP was defined as achieving the Trifecta, characterized by the contemporary absence of postoperative complications within 3 months, a 3-month postoperative maximum flow rate (Qmax) > 15 mL/s, and no urinary incontinence at 3 months postoperatively. RESULTS: Trifecta achievement at 3 months post-surgery was observed in 37 (52%) patients. Patients with Trifecta achievement exhibited a lower preoperative IPSS-quality of life score (QoL) (4.1 vs. 4.5, P = 0.016) and a thinner preoperative peripheral zone thickness (PZT) on MRI (7.9 vs.10.3 mm, P < 0.001). In the multivariable regression analysis, a preoperative IPSS-QoL score < 5 (OR 3.98; 95% CI, 1.21-13.07; P = 0.017) and PZT < 9 mm (OR 11.51; 95% CI, 3.51-37.74; P < 0.001) were significant predictors of Trifecta achievement after HoLEP. CONCLUSIONS: Alongside the preoperative QoL score, PZT measurement in prostate MRI can serve as an objective predictor of successful HoLEP. Our results underscore an additional utility of prostate MRI beyond its role in excluding concurrent prostate cancer.

Mesial temporal atrophy in preoperative MRI rather than steep Trendelenburg position is associated with postoperative delirium in patients undergoing a major urologic surgery.

PURPOSE: To investigate whether steep Trendelenburg in a major urologic surgery is associated with postoperative delirium, and to examine other potential clinical and radiologic factors predictive of postoperative delirium. METHODS: 182 patients who received a major urologic surgery and underwent a 3.0-T brain MRI scan within 1 year prior to the date of surgery were retrospectively enrolled. Preoperative brain MRIs were used to analyze features related to small vessel disease burden and mesial temporal atrophy. Presence of a significant mesial temporal atrophy was defined as Scheltens' scale ≥ 2. Patients' clinico-demographic data and MRI features were used to identify significant predictors of postoperative delirium using the logistic regression analysis. Independent predictors found significant in the univariate analysis were further evaluated in the multivariate analysis. RESULTS: Incidence of postoperative delirium was 6.0%. Patients with postoperative delirium had lower body mass index (21.3 vs. 25.0 kg/m2, P = 0.003), prolonged duration of anesthesia (362.7 vs. 224.7 min, P < 0.001) and surgery (302.2 vs. 174.5 min, P < 0.001), and had more significant mesial temporal atrophy (64% vs. 30%, P = 0.046). In the univariate analysis, female sex, type of surgery (radical prostatectomy over cystectomy), prolonged duration of anesthesia (≥ 6 h), and presence of a significant mesial temporal atrophy were significant predictors (all P-values < 0.050), but only the presence of significant mesial temporal atrophy was significant in the multivariate analysis [odds ratio (OR), 3.69; 95% CI 0.99-13.75; P = 0.046]. CONCLUSION: Steep Trendelenburg was not associated with postoperative delirium. Significant mesial temporal atrophy (Scheltens' scale ≥ 2) in preoperative brain MRI was predictive of postoperative delirium. TRIAL REGISTRATION: Not applicable.

Postoperative analgesic effects of the quadratus lumborum block in pediatric patients: a systematic review and meta-analysis.

Background: This study assessed the postoperative analgesic efficacy and safety of the quadratus lumborum block (QLB) in pediatric patients. Methods: Electronic databases were searched for studies comparing the QLB to conventional analgesic techniques in pediatric patients. The primary outcome was the need for rescue analgesia 12 and 24 hours after surgery. Secondary outcomes covered the Face-Legs-Activity-Cry-Consolability Scale (FLACC) scores at various time points; parental satisfaction; time to the first rescue analgesia; hospitalization time; block execution time; block failure rates, and adverse events. Results: Sixteen randomized controlled trials were analyzed involving 1,061 patients. The QLB significantly reduced the need for rescue analgesia both at 12 and 24 hours after surgery (12 hours, relative risk [RR]: 0.45; 95% confidence interval [CI]: 0.01, 0.88; 24 hours, RR: 0.51; 95% CI: 0.31, 0.70). In case of 24 hours after surgery, type 1 QLB significantly reduced the need for rescue analgesia (RR: 0.56; 95% CI: 0.36, 0.76). The QLB also exhibited lower FLACC scores at 1 hour (standardized mean difference [SMD]: -0.87; 95% CI: -1.56, -0.18) and 6 hours (SMD: -1.27; 95% CI: -2.33, -0.21) following surgery when compared to non-QLB. Among QLBs, type 2 QLB significantly extended the time until the first rescue analgesia (SMD: 1.25; 95% CI: 0.84, 1.67). No significant differences were observed in terms of parental satisfaction, hospitalization time, block execution time, block failure, or adverse events between QLB and non-QLB groups. Conclusions: The QLB provides non-inferior analgesic efficacy and safety to conventional methods in pediatric patients.

Artificial intelligence model predicting postoperative pain using facial expressions: a pilot study.

PURPOSE: This study aimed to assess whether an artificial intelligence model based on facial expressions can accurately predict significant postoperative pain. METHODS: A total of 155 facial expressions from patients who underwent gastric cancer surgery were analyzed to extract facial action units (AUs), gaze, landmarks, and positions. These features were used to construct various machine learning (ML) models, designed to predict significant postoperative pain intensity (NRS ≥ 7) from less significant pain (NRS < 7). Significant AUs predictive of NRS ≥ 7 were determined and compared to AUs known to be associated with pain in awake patients. The area under the receiver operating characteristic curves (AUROCs) of the ML models was calculated and compared using DeLong's test. RESULTS: AU17 (chin raising) and AU20 (lip stretching) were found to be associated with NRS ≥ 7 (both P ≤ 0.004). AUs known to be associated with pain in awake patients did not show an association with pain in postoperative patients. An ML model based on AU17 and AU20 demonstrated an AUROC of 0.62 for NRS ≥ 7, which was inferior to a model based on all AUs (AUROC = 0.81, P = 0.006). Among facial features, head position and facial landmarks proved to be better predictors of NRS ≥ 7 (AUROC, 0.85-0.96) than AUs. A merged ML model that utilized gaze and eye landmarks, as well as head position and facial landmarks, exhibited the best performance (AUROC, 0.90) in predicting significant postoperative pain. CONCLUSION: ML models using facial expressions can accurately predict the presence of significant postoperative pain and have the potential to screen patients in need of rescue analgesia. TRIAL REGISTRATION NUMBER: This study was registered at ClinicalTrials.gov (NCT05477303; date: June 17, 2022).

Differentiation between hepatic angiomyolipoma and hepatocellular carcinoma in individuals who are not at-risk for hepatocellular carcinoma.

PURPOSE: To develop a practical methodfor differentiating hepatocellular carcinoma (HCC) from angiomyolipoma (AML) in individuals who are not at-risk for HCC. METHOD: We retrospectively enrolled consecutive patients who underwent gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) and pathological confirmation between January 2008 and April 2022. Patients who underwent prior treatment, those with multiple lesions, or those at-risk for HCC were excluded. The training cohort included patients with pathological confirmation between 2008 and 2019, whereas the validation cohort included the remaining cases. Independent reviews of the MRI were performed by two reviewers. Using the clinical and MRI findings, we developed AML-HCC score using Firth's logistic regression in the training cohort, and the diagnostic performance was validated in the validation cohort. RESULTS: Of the 206 patients, 156 were assigned to the training cohort (25 and 131 patients with AML and HCC, respectively) and 50 were assigned to the validation cohort (4 and 46 patients with AML and HCC, respectively). The AML-HCC score was defined as the sum of female (score 1), early draining vein (score 2), T2 homogeneity (score 1), necrosis or severe ischaemia (score -2), and HBP hyperintensity to spleen (score -1). When the AML-HCC score was ≥1, the sensitivity and specificity were 80% and 95% for the training cohort and 100% and 80% for the validation cohort, respectively. CONCLUSIONS: We developed and validated an AML-HCC score to differentiate between AML and HCC in individuals who are not at-risk for HCC, and our model demonstrated good diagnostic performance.

Steatotic hepatocellular carcinoma: Association of MRI findings to underlying liver disease and clinicopathological characteristics.

BACKGROUND & AIMS: Fatty change is commonly observed in hepatocellular carcinoma (HCC); however, the characteristics of steatotic and steatohepatitic HCCs are not well understood. METHODS: This retrospective study included patients with HCCs who underwent resection between January 2014 and December 2019 to evaluate clinicopathological and magnetic resonance imaging features. Tumours were categorized as magnetic resonance imaging-steatotic, pathology-steatotic and steatohepatitic HCCs and were defined as HCCs with ≥50% steatosis on in-and-oppose phase images, ≥34% tumour cells with lipid droplets and ≥50% tumour areas with steatohepatitic features on light microscopy respectively. RESULTS: Of 465 HCCs, 38 (8%), 23 (5%) and 15 (3%) were diagnosed as magnetic resonance imaging-steatotic, pathology-steatotic and steatohepatitic HCCs respectively. These HCC variants were less likely to be associated with hepatitis B virus infections than with type 2 diabetes mellitus, metabolic syndrome, non-tumour liver steatosis and steatohepatitis. Moreover, microvascular invasion was less likely to be associated with them than either tumour size or differentiation. Type 2 diabetes and non-tumour steatosis were independent risk factors for magnetic resonance imaging-steatotic HCCs. Pathology-steatotic HCCs and steatohepatitic HCCs were significantly associated with magnetic resonance imaging-steatotic HCCs. A targetoid appearance in the transitional or hepatobiliary phase was also more prevalent in steatohepatitic-HCCs than in non-steatohepatitic-HCCs. When magnetic resonance imaging-steatotic HCCs were combined with one or more ancillary features, the sensitivity and specificity were 60% and 97% respectively. CONCLUSION: Underlying fatty liver disease and metabolic syndrome are strongly associated with both steatotic and steatohepatitic HCCs. Clinicoradiological characteristics help identify steatohepatitic HCC with high specificity.

Hepatobiliary phase signal intensity: A potential method of diagnosing HCC with atypical imaging features among LR-M observations.

Herein, we assessed whether hepatobiliary phase (HBP) signal intensity (SI) can be used to differentiate HCC and non-HCC malignancies within LR-M observations. 106 LR-M patients based on LI-RADS v2018 who underwent gadoxetate-disodium magnetic resonance imaging and surgery from January 2009 to December 2018 were included. SI of LR-M observation on HBP was analyzed by two radiologists and categorized into dark, low and iso-to-high groups. Tumor was classified as dark when more than 50% of tumor showed hypointensity compared to spleen, as low when more than 50% of tumor showed hyperintensity compared to spleen but hypointensity compared to liver parenchyma, and as iso-to-high if there was even a focal iso-intensity or hyperintensity compared to liver parenchyma. Analysis of clinicopathological factors and association between imaging and histology was performed. Out of 106 LR-M, 42 (40%) were showed dark, 61 (58%) showed low, and 3 (3%) showed iso-to-high SI in HBP. Three iso-to-high SI LR-M were HCCs (P = 0.060) and their major histologic differentiation was Edmondson grade 1 (P = 0.001). 43 out of 61 (71%) low SI LR-M were iCCA or cHCC-CCA (P = 0.002). Inter-reader agreement of HBP SI classification was excellent, with a kappa coefficient of 0.872. LR-M with iso-to-high SI in HBP is prone to being HCC while LR-M with low SI in HBP is prone to being tumor with fibrous stroma such as iCCA and cHCC-CCA. Classification of LR-M based on HBP SI may be a helpful method of differentiating HCC from non-HCC malignancies.

Should Threshold Growth Be Considered a Major Feature in the Diagnosis of Hepatocellular Carcinoma Using LI-RADS?

OBJECTIVE: Based on the Liver Imaging Reporting and Data System version 2018 (LI-RADS, v2018), this study aimed to analyze LR-5 diagnostic performance for hepatocellular carcinoma (HCC) when threshold growth as a major feature is replaced by a more HCC-specific ancillary feature, as well as the frequency of threshold growth in HCC and non-HCC malignancies and its association with tumor size. MATERIALS AND METHODS: This retrospective study included treatment-naive patients who underwent gadoxetate disodium-enhanced MRIs for focal hepatic lesions and surgery between January 2009 and December 2016. The frequency of major and ancillary features was evaluated for HCC and non-HCC malignancies, and the LR-category was assessed. Ancillary features that were significantly more prevalent in HCC were then used to either replace threshold growth or were added as additional major features, and the diagnostic performance of the readjusted LR category was compared to the LI-RADS v2018. RESULTS: A total of 1013 observations were analyzed. Unlike arterial phase hyperenhancement, washout, or enhancing capsule which were more prevalent in HCCs than in non-HCC malignancies (521/616 vs. 18/58, 489/616 vs. 19/58, and 181/616 vs. 5/58, respectively; p < 0.001), threshold growth was more prevalent in non-HCC malignancies than in HCCs (11/23 vs. 17/119; p < 0.001). The mean size of non-HCC malignancies showing threshold growth was significantly smaller than that of non-HCC malignancies without threshold growth (22.2 mm vs. 42.9 mm, p = 0.040). Similar results were found for HCCs; however, the difference was not significant (26.8 mm vs. 33.1 mm, p = 0.184). Additionally, Fat-in-nodule was more frequent in HCCs than in non-HCC malignancies (99/616 vs. 2/58, p = 0.010). When threshold growth and fat-in-nodule were considered as ancillary and major features, respectively, LR-5 sensitivity (73.2% vs. 73.9%, p = 0.289) and specificity (98.2% vs. 98.5%, p > 0.999) were comparable to the LI-RADS v2018. CONCLUSION: Threshold growth is not a significant diagnostic indicator of HCC and is more common in non-HCC malignancies. The diagnostic performance of LR-5 was comparable when threshold growth was recategorized as an ancillary feature and replaced by a more HCC-specific ancillary feature.

Update on Pathologic and Radiologic Diagnosis of Combined Hepatocellular-Cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a malignant primary liver carcinoma characterized by the unequivocal presence of both hepatocytic and cholangiocytic differentiation within the same tumor. Recent research has highlighted that cHCC-CCAs are more heterogeneous than previously expected. In the updated consensus terminology and WHO 2019 classification, "classical type" and "subtypes with stem-cell features" of the WHO 2010 classification are no longer recommended. Instead, it is recommended that the presence and percentages of various histopathologic components and stem-cell features be mentioned in the pathologic report. The new terminology and classification enable the exchange of clearer and more objective information about cHCC-CCAs, facilitating multi-center and multi-national research. However, there are limitations to the diagnosis of cHCC-CCA by imaging and biopsy. cHCC-CCAs showing typical imaging findings of HCC could be misdiagnosed as HCC and subjected to inappropriate treatment, if other clinical findings are not sufficiently considered. cHCC-CCAs showing at least one of the CCA-like imaging features or unusual clinical features should be subjected to biopsy. There may be a sampling error for the biopsy diagnosis of cHCC-CCA. An optimized diagnostic algorithm integrating clinical, radiological, and histopathologic information of biopsy is required to resolve these diagnostic pitfalls.

Gadoxetic acid-enhanced MRI of hepatocellular carcinoma: Diagnostic performance of category-adjusted LR-5 using modified criteria.

The Liver Imaging Reporting and Data System (LI-RADS) is widely adopted for the noninvasive diagnosis of hepatocellular carcinoma (HCC). Herein, possible strategies to improve the diagnostic performance of LR-5 without reducing specificity for HCC were investigated. This retrospective study included 792 patients who underwent gadoxetate disodium-enhanced magnetic resonance imaging. Hepatic observations were categorized according to LI-RADS v2018 and categories were readjusted by upgrading LR4 to LR5 using ancillary features, arterial phase hyperenhancement (APHE) interpreted with subtraction images, indication of no washout when APHE was absent, extension of washout to the transitional phase, and subthreshold growth as a major feature. Based on LI-RADS v2018, LR-5 showed a sensitivity of 71.9% and a specificity of 97.9% for the diagnosis of HCC. Category-readjusted LR-5 after upgrading LR-4 to LR-5 using ancillary features favoring HCC in particular, subthreshold growth as a major feature, extending washout to transitional phase and APHE interpreted using subtraction images showed significantly increased sensitivity (P<0.001) without decreased specificity (Ps>0.05). The sensitivity of LR-5 can be improved without loss of specificity via category readjustment using AFs favoring HCC in particular, subthreshold growth as a major feature, extending washout to transitional phase and APHE interpreted with subtraction images.

Feasibility of Simultaneous Multislice Acceleration Technique in Diffusion-Weighted Magnetic Resonance Imaging of the Rectum.

OBJECTIVE: To assess the feasibility of simultaneous multislice-accelerated diffusion-weighted imaging (SMS-DWI) of the rectum in comparison with conventional DWI (C-DWI) in rectal cancer patients. MATERIALS AND METHODS: This study included 65 patients with initially-diagnosed rectal cancer. All patients underwent C-DWI and SMS-DWI with acceleration factors of 2 and 3 (SMS2-DWI and SMS3-DWI, respectively) using a 3T scanner. Acquisition times of the three DWI sequences were measured. Image quality in the three DWI sequences was reviewed by two independent radiologists using a 4-point Likert scale and subsequently compared using the Friedman test. Apparent diffusion coefficient (ADC) values for rectal cancer and the normal rectal wall were compared among the three sequences using repeated measures analysis of variance. RESULTS: Acquisition times using C-DWI, SMS2-DWI, and SMS3-DWI were 173 seconds, 107 seconds, (38.2% shorter than C-DWI), and 77 seconds (55.5% shorter than C-DWI), respectively. For all image quality parameters other than distortion (margin sharpness, artifact, lesion conspicuity, and overall image quality), C-DWI and SMS2-DWI yielded better results than did SMS3-DWI (Ps < 0.001), with no significant differences observed between C-DWI and SMS2-DWI (Ps ≥ 0.054). ADC values of rectal cancer (p = 0.943) and normal rectal wall (p = 0.360) were not significantly different among C-DWI, SMS2-DWI, and SMS3-DWI. CONCLUSION: SMS-DWI using an acceleration factor of 2 is feasible for rectal MRI resulting in substantial reductions in acquisition time while maintaining diagnostic image quality and similar ADC values to those of C-DWI.

Genetic variations in MicroRNA genes and cancer risk: A field synopsis and meta-analysis.

BACKGROUND: Cancer risk has been associated with certain gene variations in microRNA (miRNA), but conflicting evidence warrants re-assessing of significant results in meta-analyses. We summarized published meta-analyses that assess the associations between miRNA polymorphism and cancers to show the validity of the findings. METHOD: We searched PubMed and investigated the results of meta-analyses published through November 2018. We re-assessed the results based on false-positive report probability (FPRP) to test the noteworthiness of the associations. RESULTS: Sixty-eight miRNA polymorphisms in 45 meta-analyses associated with cancer were included. Four (7.4%) and sixteen (25.0%) single nucleotide polymorphisms (SNPs) were noteworthy (FPRP < 0.2) at a prior probability of 0.001 for interesting candidate genes and a statistical power to detect an odds ratio (OR) of 1.1 and 1.5, respectively. The four miRNA SNPs noteworthy at an OR of 1.1 were as follows: miR-146a/rs2910164 Cvs.G; miR-27a/rs895819 Cvs.T; miR-423/rs6505162 Cvs.A; and miR-605/rs2043556 Cvs.T. The 16 SNPs noteworthy at an OR of 1.5 include the four genotype comparisons at an OR of 1.1, and the additional 12 genotype comparisons were as follows: miR-196a2/rs11614913 Tvs.C; miR-27a/rs895819 GGvs.AA + AG; miR-196a2/rs11614913 C vs.T; miR-146a/rs2910164 Gvs.C; miR-196a2/rs11614913 Tvs.C; miR-146a/rs2910164 Cvs.G; miR-499/rs3746444 homozygous model; miR-146a/rs2910164 CCvs.GG + GC; miR-499/rs3746444 TCvs.TT; miR-499/rs3746444 GAvs.AA; miR-146a/rs2910164 CCvs.GG; and miR-499/rs3746444 Gvs.A. No association was noteworthy at a prior probability of 0.000001. CONCLUSION: Out of 68 published associations of miRNA polymorphisms with cancer, sixteen have shown noteworthiness in our re-assessing meta-analysis. Our findings summarize the results of meta-analyses on the association of cancer with SNPs and underline the importance of interpreting results with caution.

Bayesian statistical methods in genetic association studies: Empirical examination of statistically non-significant Genome Wide Association Study (GWAS) meta-analyses in cancers: A systematic review.

A Bayesian statistical method was developed to assess the noteworthiness of a single nucleotide polymorphism (SNP)-phenotype association that shows statistical significance in various observational studies, but it has seldom been applied to GWAS meta-analyses in cancers. Data (i.e. allelic frequency, odds ratio, 95% confidence interval, etc.) on various SNP-cancer associations were extracted from meta-analysis of GWAS and the National Human Genome Research Institute (NHGRI) Catalog of Published GWAS and were used to compute the false positive report probability (FPRP) and Bayesian false discovery probability (BFDP) to evaluate the noteworthiness of SNP-cancer associations. Independent paired t-tests showed a direct relationship between SNP-cancer P-values and both FPRP and BFDP estimates. However, a discrepancy in the number of noteworthy associations between P-value comparison and either FPRP or BFDP was found using data extracted from meta-analyses of GWAS and the GWAS Catalog. Most P-values of associations with nonsignificant P-values but with noteworthy FPRP and BFDP estimates were within the range of 10-6 to 5 × 10-8. A poorly selected genome-wide significance threshold and inclusion of a nonsignificant SNP-phenotype association into the noteworthy test can, with either noteworthy FPRP or BFDP computation, give a false impression of noteworthiness for a nonsignificant association.

Dapsone as a potential treatment option for Henoch-Schönlein Purpura (HSP).

Henoch-Schönlein Purpura (HSP, IgA vasculitis) is an immunoglobulin A (IgA) mediated disorder characterized by systemic vasculitis with variable presentation, frequently affecting the skin, mucous membrane, joints, kidneys, and rarely lungs and the central nervous system. Interestingly, enhanced production of interleukin-8 (IL-8) levels are found during active disease and increased levels have been reported in supernatants from human umbilical venous endothelial cells after stimulation with sera from patients affected by HSP. While corticosteroid therapy is currently the recommended treatment for HSP, dapsone, an anti-leprosy agent, has also recently been suggested to have therapeutic efficacy due to its ability to suppress IL-8. Moreover, in addition to IL-8 suppression, dapsone has been reported to exert various anti-inflammatory effects by inhibiting the generation of toxic free radicals, myeloperoxidase mediated halogenation that converts H2O2 to HOCl, leukocyte chemotaxis, production of tumor necrosis factor, and other anti-inflammatory molecules. This review aims to provide a solid hypothesis for the pathogenesis of vasculitis in HSP. Moreover, we highlight potential mechanistic actions of dapsone in hopes that dapsone may be considered as an alternative viable treatment for patients affected by HSP.

IBD immunopathogenesis: A comprehensive review of inflammatory molecules.

Inflammatory molecules play a crucial role in the pathogenesis of inflammatory bowel disease (IBD) such as ulcerative colitis and Crohn's disease, both of which are chronic inflammatory conditions of the gastrointestinal tract. Abnormal expressions of pro- and anti-inflammatory molecules have been described to cause an imbalance to the gut innate and adaptive immunity, and recently a large portion of research in IBD has been geared towards identifying novel molecules that may be used as potential therapeutic targets. Understanding of these inflammatory molecules has suggested that although ulcerative colitis and Crohn's disease share many common clinical symptoms and signs, they are in fact two separate clinical entities characterized by different immunopathogenesis. In this review, we comprehensively discuss the roles of numerous inflammatory molecules including but not limited to cytokines, chemokines, inflammasomes, microRNAs and neuropeptides and their expression status in ulcerative colitis and Crohn's disease in relation to their effects on the overall intestinal inflammatory process.

From cell biology to immunology: Controlling metastatic progression of cancer via microRNA regulatory networks.

Recently, the study of microRNAs has expanded our knowledge of the fundamental processes of cancer biology and the underlying mechanisms behind tumor metastasis. Extensive research in the fields of microRNA and its novel mechanisms of actions against various cancers has more recently led to the trial of a first cancer-targeted microRNA drug, MRX34. Yet, these microRNAs are mostly being studied and clinically trialed solely based on the understanding of their cell biologic effects, thus, neglecting the important immunologic effects that are sometimes opposite of the cell biologic effects. Here, we summarize both the cell biologic and immunologic effects of various microRNAs and discuss the importance of considering both effects before using them in clinical settings. We stress the importance of understanding the miRNA's effect on cancer metastasis from a "systems" perspective before developing a miRNA-targeted therapeutic in treating cancer metastasis.

A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs.

Packaging multiple small interfering RNA (siRNA) molecules into nanostructures at precisely defined ratios is a powerful delivery strategy for effective RNA interference (RNAi) therapy. We present a novel RNA nanotechnology based approach to produce multiple components of polymerized siRNA molecules that are simultaneously self-assembled and densely packaged into composite sponge-like porous microstructures (Multi-RNAi-MSs) by rolling circle transcription. The Multi-RNAi-MSs were designed to contain a combination of multiple polymeric siRNA molecules with precisely controlled stoichiometry within a singular microstructure by manipulating the types and ratios of the circular DNA templates. The Multi-RNAi-MSs were converted into nanosized complexes by polyelectrolyte condensation to manipulate their physicochemical properties (size, shape, and surface charge) for favorable delivery, while maintaining the multifunctional properties of the siRNAs for combined therapeutic effects. These Multi-RNAi-MS systems have great potential in RNAi-mediated biomedical applications, for example, for the treatment of cancer, genetic disorders, and viral infections.