Preoperative risk score for mortality within 3 years of visceral segment fenestrated endovascular aortic repair.

OBJECTIVE: The purpose of this study was to create a risk score for the event of mortality within 3 years of complex fenestrated visceral segment endovascular aortic repair utilizing variables existing at the time of preoperative presentation. METHODS: After exclusions, 1916 patients were identified in the Vascular Quality Initiative who were included in the analysis. The first step in development of the risk score was univariable analysis for the primary outcome of mortality within 3 years of surgery. χ2 analysis was performed for categorical variables, and comparison of means with independent Student t-test was performed for ordinal variables. Variables that achieved a univariable P value less than 0.1 were then placed into Cox regression multivariable time dependent analysis for the development of mortality within 3 years. Variables that achieved a multivariable significance of less than 0.1 were utilized for the risk score, with point weighting based on the beta-coefficient. Variables with a beta coefficient of 0.25 to 0.49 were assigned 1 point, 0.5 to 0.74 2 points, 0.75 to 0.99 3 points, and 1.0 to 1.25 4 points. A cumulative score for each patient was then summed, the percentage of patients at each score experiencing mortality within 3 weeks was then calculated, and a comparison of score outcomes was conducted with binary logistic regression. Area under the curve analysis was performed. RESULTS: The primary outcome of mortality within 3 years of surgery occurred in 12.8% of patients (245/1916). The mean age for the study population was 73.35 years (standard deviation [SD], 8.26 years). The mean maximal abdominal aortic aneurysm (AAA) diameter was 60.43 mm (SD, 10.52 mm). The mean number of visceral vessels stented was 3.3 (SD, 0.76). Variables present at the time of surgery that were included in the risk score were: hemodialysis (3 points); age >87, chronic obstructive pulmonary disease, hypertension, AAA diameter >77 mm (all 2 points); and body mass index <20 kg/m2, female sex, congestive heart failure, active smoking, chronic renal insufficiency, age 80 to 87 years, and AAA diameter 67 to 77 mm (all 1 point). BMI >30 kg/m2 (mean, 34.46 kg/m2) and age <67 years were protective (-1 point). Testing the model resulted in an area under the curve of 0.706. Hosmer and Lemeshow goodness of fit test for logistic regression utilizing the 15 different risk score total groups revealed a model predictive accuracy of 87.3%. Significant escalations in 3-year mortality were noted to occur at scores of 6 and greater. Mean AAA diameter was significantly larger for patients who had higher risk scores (P < .001). CONCLUSIONS: A novel risk score for mortality within 3 years of fenestrated visceral segment aortic endograft has been developed that has excellent accuracy in predicting which patients will survive and derive the strongest benefit from intervention. This facilitates risk-benefit analysis and counseling of patients and families with realistic long-term expectations. This potentially enhances patient-centered decision-making.

Correlation between triglyceride glucose-body mass index and hypertension risk: evidence from a cross-sectional study with 60,283 adults in eastern China.

BACKGROUND: Insulin resistance (IR) and obesity are established risk factors for hypertension, with triglyceride-glucose (TyG) serving as a recognized surrogate marker for IR. The aim of this study was to investigate the association between TyG-BMI and hypertension in the general population. METHODS: A total of 60,283 adults aged ≥18 years who underwent face-to-face questionnaires, anthropometric measurements, and laboratory examination were included in this study. Multivariable logistic regression models and receiver operating characteristic curve (ROC) were used to determine the association between TyG-BMI and hypertension. The restricted cubic spline model was used for the dose-response analysis. RESULTS: After fully adjusting for confounding variables, multivariate logistic regression model showed a stable positive association between TyG-BMI and hypertension (OR: 1.61 per SD increase; 95% CI: 1.55-1.67; P-trend < 0.001). The multivariate adjusted OR and 95% CI for the highest TyG-BMI quartile compared with the lowest quartile were 2.52 (95% CI 2.28-2.78). Dose-response analysis using restricted cubic spline confirmed that the association between TyG-BMI index and hypertension was linear. Subgroup analyses showed that stronger associations between TyG-BMI index and hypertension were detected in young and middle-aged individuals (P for interaction < 0.05). ROC analysis showed that TyG-BMI index could better predict the risk of hypertension than other parameters (TyG-BMI cut-off value: 207.105, AUC: 0.719, sensitivity 65.5%, specificity 66.8%), particularly among young and middle-aged people. CONCLUSION: The TyG-BMI index was independently associated with hypertension in the study population. Further studies are required to confirm this relationship.

Arteriovenous Fistula Maturation in Patients with Ipsilateral Versus Contralateral Tunneled Dialysis Catheter: A Systematic Review and Meta-analysis.

BACKGROUND: Although it is evident that a prior history of tunneled dialysis catheter (TDC) affects arteriovenous fistula (AVF) function, it is unclear whether its location (contralateral versus ipsilateral to AVF) has any effect on AVF maturation and failure rates. We aimed to document this possible effect. METHODS: This systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies comparing outcomes between patients with contralateral TDC (CONTRA group) and those with ipsilateral one (IPSI group) were examined for inclusion. A random effects model meta-analysis of the odds ratio (OR) was conducted. Primary outcomes were AVF functional maturation, assisted maturation, and failure rates. RESULTS: Four eligible studies comprising 763 patients were included in the meta-analysis. There were no significant differences in terms of AVF functional maturation (OR: 1.49; 95% confidence interval [CI]: 0.64-3.47; I2 = 83.4%), assisted maturation (OR: 0.59; 95% CI: 0.29-1.19; I2 = 61.4%), and failure rates (OR: 0.67; 95% CI: 0.29-1.58; I2 = 83.3%) between the 2 study groups. CONCLUSIONS: TDC laterality seems not to affect fistula maturation rate in patients requiring TDC placement and concurrent AVF creation, but rather, vein- and patient-related characteristics might play a more important role in choosing TDC access site. Further studies are needed to validate these results.

Risk Factors for Lower Extremity Minor Amputation Conversion to Major Amputation.

BACKGROUND: Minor lower extremity amputations (LEAs) have become an important part of the limb salvage approach but are not as benign as previously thought. This study investigates the difference in outcome between toe/ray versus midfoot amputations and the risk factors for major amputation conversion associated with each procedure. METHODS: We performed retrospective chart review of foot amputation patients at a single tertiary care medical center with a primary end point of conversion to major amputation and secondary end points of 1-year wound healing and mortality rate. We collected data on relevant medical comorbidities, noninvasive vascular imaging, revascularization, repeat amputations, wound healing rate, and 1-year mortality. Patients were separated into toe/ray amputations versus midfoot amputation groups and compared using descriptive statistics, Chi-squared tests, Cox proportional hazards, and a multivariate logistic regression model. RESULTS: A total of 375 amputations were included in the analysis. 65.3% (245 patients) included toe/ray amputations and 34.7% (130 patients) included midfoot amputations. We compared these 2 cohorts with regard to their rate of conversion to repeat minor and/or major amputation in addition to overall mortality. The toe/ray group underwent more repeat minor amputations within 1 year after index amputation (34.7% vs. 21.5%, P = 0.008) and wound healing (epithelization) at 90 days was also higher in this group. The midfoot group had a higher conversion to major LEA within 1 year on univariate analysis (20.8 vs. 6.9%, P < 0.001). Overall 1-year mortality was 6.17% and there was no significant difference between groups. CONCLUSIONS: While there is a consistency with previous studies that found no significant overall difference in mortality between types of minor LEA, we have extended this previous work by demonstrating the independent risk factors for conversion to major amputation between types of minor LEA. Comparing these 2 groups will assist surgeons in choosing the appropriate level of amputations and will enhance patient's understanding of their chance of wound healing and risk of repeat amputation.

Retinopathy as a predictive indicator for significant hepatic fibrosis according to T2DM status: A cross-sectional study based on the national health and nutrition examination survey data.

INTRODUCTION AND OBJECTIVES: Type 2 Diabetes Mellitus (T2DM), a prevalent metabolic disorder, often coexists with a range of complications, with retinopathy being particularly common. Recent studies have shed light on a potential connection between diabetic retinopathy (DR) and hepatic fibrosis, indicating a possible shared pathophysiological foundation in T2DM. This study investigates the correlation between retinopathy and hepatic fibrosis among individuals with T2DM, as well as evaluates the diagnostic value of DR for significant hepatic fibrosis. MATERIALS AND METHODS: Our cross-sectional analysis incorporated 5413 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. The Fibrosis-4 score (FIB-4) classified hepatic fibrosis into different grades (F0-F4), with significant hepatic fibrosis marked as F2 or higher. Retinopathy severity was determined using retinal imaging and categorized into four levels. The analysis of variance or Chi-square tests facilitated group comparisons. Additionally, the receiver operating characteristic (ROC) analysis appraised the predictive accuracy of retinopathy for significant hepatic fibrosis in the T2DM population. RESULTS: Among 5413 participants, the mean age was 59.56 ± 12.41, with 50.2% male. And 20.6% were diagnosed with T2DM. Hepatic fibrosis grading was positively associated with retinopathy severity (OR [odds ratio]: 1.521, 95%CI [confidence interval]: 1.152-2.008, P = 0.003) across the entire population. The association was amplified in the T2DM population according to Pearson's analysis results. The ROC curve demonstrated retinopathy's diagnostic capacity for significant hepatic fibrosis in the T2DM population (AUC [area under curve] = 0.72, 95%CI: 0.651-0.793, P < 0.001). CONCLUSIONS: Retinopathy could serve as an independent predictor of significant hepatic fibrosis in T2DM population. Ophthalmologists are advised to closely monitor T2DM patients with retinopathy.

Variations and thicknesses of anterior belly of the digastric muscle: an ultrasonographic study.

PURPOSE: This study aims to evaluate the anatomy and anatomical variations of the anterior belly of the digastric muscle. METHODS: Hundred and fifty one ultrasonographic images of the digastric muscle pairs were evaluated in Near East University Faculty of Dentistry Department of Dentomaxillofacial Radiology. Morphological variations were recorded using the classification of the digastric muscle into 12 types by Kim et al. For the analysis, the Mann-Whitney U test and Chi-square test were used, and for the correlational analysis, Spearman's rho test was applied. P < 0.05 was considered statistically significant in all tests. RESULTS: Seventy female and 81 male patients aged 19-60 years were evaluated. Type 1 digastric muscle was observed in 145 of 151 patients, Type 2 in 3 patients, and Type 7 in 3 patients. The thicknesses of the right and left digastric muscles were measured, and a statistically significant difference was observed between the groups when the genders were compared. It was observed that both right and left digastric muscle thicknesses were higher in males than females. There was a statistically significant positive high correlation between right and left digastric muscle thicknesses (p = 0.000; r = 0.736). No statistically significant difference was found between genders (p = 0.596) in terms of anatomical variations. CONCLUSION: Considering that the variations of the digastric muscle may have a clinical significance role, the normal anatomy and variations of this muscle should be well known by maxillofacial surgeons and radiologists.

Permutation Tests for Assessing Potential Non-Linear Associations between Treatment Use and Multivariate Clinical Outcomes.

In many psychometric applications, the relationship between the mean of an outcome and a quantitative covariate is too complex to be described by simple parametric functions; instead, flexible nonlinear relationships can be incorporated using penalized splines. Penalized splines can be conveniently represented as a linear mixed effects model (LMM), where the coefficients of the spline basis functions are random effects. The LMM representation of penalized splines makes the extension to multivariate outcomes relatively straightforward. In the LMM, no effect of the quantitative covariate on the outcome corresponds to the null hypothesis that a fixed effect and a variance component are both zero. Under the null, the usual asymptotic chi-square distribution of the likelihood ratio test for the variance component does not hold. Therefore, we propose three permutation tests for the likelihood ratio test statistic: one based on permuting the quantitative covariate, the other two based on permuting residuals. We compare via simulation the Type I error rate and power of the three permutation tests obtained from joint models for multiple outcomes, as well as a commonly used parametric test. The tests are illustrated using data from a stimulant use disorder psychosocial clinical trial.

Conversion to open surgery in obese patients undergoing minimally invasive distal pancreatectomy: results from a multicenter analysis.

BACKGROUND: Although minimally invasive distal pancreatectomy (MIDP) is considered a standard approach it still presents a non-negligible rate of conversion to open that is mainly related to some difficulty factors, as obesity. The aim of this study is to analyze the preoperative factors associated with conversion in obese patients with MIDP. METHODS: In this multicenter study, all obese patients who underwent MIDP at 18 international expert centers were included. The preoperative factors associated with conversion to open surgery were analyzed. RESULTS: Out of 436 patients, 91 (20.9%) underwent conversion to open, presenting higher blood loss, longer operative time and similar rate of major complications. Twenty (22%) patients received emergent conversion. At univariate analysis, the type of approach, radiological invasion of adjacent organs, preoperative enlarged lymphnodes and ASA ≥ III were significantly associated with conversion to open. At multivariate analysis, robotic approach showed a significantly lower conversion rate (14.6 % vs 27.3%, OR = 2.380, p = 0.001). ASA ≥ III (OR = 2.391, p = 0.002) and preoperative enlarged lymphnodes (OR = 3.836, p = 0.003) were also independently associated with conversion. CONCLUSION: Conversion rate is significantly lower in patients undergoing robotic approach. Radiological enlarged lymphnodes and ASA ≥ III are also associated with conversion to open. Conversion is associated with poorer perioperative outcomes, especially in case of intraoperative hemorrhage.

Predictive score for identifying intrahepatic cholangiocarcinoma patients without lymph node metastasis: a basis for omitting lymph node dissection.

BACKGROUND: This study aimed to develop a predictive score for intrahepatic cholangiocarcinoma (ICC) in patients without lymph node metastasis (LNM) using preoperative factors. METHODS: A retrospective analysis of 113 ICC patients who underwent liver resection with systemic lymph node dissection between 2002 and 2021 was conducted. A multivariate logistic regression analysis was used as a predictive scoring system for node-negative patients based on the ß coefficients of preoperatively available factors. RESULTS: LNM was observed in 36 patients (31.9%). Four factors were associated with LNM: suspicion of LNM on MDCT (odds ratio [OR] 13.40, p < 0.001), low-vascularity tumor (OR 6.28, p = 0.005), CA19-9 ≥500 U/mL (OR 5.90, p = 0.010), and tumor location in the left lobe (OR 3.67, p = 0.057). The predictive scoring system was created using these factors (assigning 3 points for suspected LNM on MDCT, 2 points for CA19-9 ≥500 U/mL, 2 points for low vascularity tumor, and 1 point for tumor location in the left lobe). A score cutoff value of 4 resulted in 0.861 sensitivity and a negative predictive value of 0.922 for detecting LNM. Notably, no patients with peripheral tumors and a score of ≤3 had LNM. CONCLUSION: The developed scoring system may effectively help identify ICC patients without LNM.

Interim monitoring in sequential multiple assignment randomized trials.

A sequential multiple assignment randomized trial (SMART) facilitates the comparison of multiple adaptive treatment strategies (ATSs) simultaneously. Previous studies have established a framework to test the homogeneity of multiple ATSs by a global Wald test through inverse probability weighting. SMARTs are generally lengthier than classical clinical trials due to the sequential nature of treatment randomization in multiple stages. Thus, it would be beneficial to add interim analyses allowing for an early stop if overwhelming efficacy is observed. We introduce group sequential methods to SMARTs to facilitate interim monitoring based on the multivariate chi-square distribution. Simulation studies demonstrate that the proposed interim monitoring in SMART (IM-SMART) maintains the desired type I error and power with reduced expected sample size compared to the classical SMART. Finally, we illustrate our method by reanalyzing a SMART assessing the effects of cognitive behavioral and physical therapies in patients with knee osteoarthritis and comorbid subsyndromal depressive symptoms.

Factors affecting the accuracy of anti-BRAF V600E immunohistochemistry results in ameloblastomas.

BACKGROUND: There are still some controversies about the results of anti-BRAF V600E-specific antibody immunohistochemistry in ameloblastomas. This study aimed to examine the accuracy of V600E-specific antibody immunohistochemistry in detection of BRAF V600E mutation in ameloblastoma tissue sections of different ages. METHODS: The BRAF V600E status of 64 ameloblastoma specimens was assessed using both Sanger sequencing and V600E-specific antibody immunohistochemistry, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The difference in V600E-specific antibody immunohistochemistry staining intensity among the three groups of ameloblastoma tissue blocks of different ages was evaluated by chi-square test. The consistency between V600E-specific antibody immunohistochemistry and DNA sequencing results and the V600E-specific antibody immunohistochemistry staining intensity of 15 paired newly-cut and 3-month storage sections of the same 15 ameloblastomas were also compared. RESULTS: For detection of BRAF V600E mutation, the V600E-specific antibody immunohistochemistry had high sensitivity (98.21% 55/56), specificity (87.5% 7/8), positive predictive value (98.21% 55/56), and negative predictive value (87.5% 7/8). Heterogeneity of the staining intensity was observed in the same tissue section, but all or none expression pattern was noticed in the solid tumor nests. The storage time of paraffin tissue blocks ranging from 2 to 14 years did not affect the V600E-specific antibody-positive staining intensity. However, the three-month storage sections showed a significant diminishment of V600E-specific antibody-positive staining signals. CONCLUSIONS: The BRAF V600E-specific antibody immunohistochemistry is suitable for routine detection of BRAF V600E mutation in ameloblastomas. The all or none expression pattern suggests the BRAF V600E mutation may be an early event in the pathogenesis of ameloblastoma.

The association between day of arrival, time of arrival, daily volume and the rate of patients that "left without being seen".

INTRODUCTION: Patients' left without being seen (LWBS) rate is used as an emergency department (ED) quality indicator. Prior research has investigated characteristics of these patients, but there are minimal studies assessing the impact of departmental variables. We evaluate the LWBS rate at a granular level, looking at its relationship to day of week, hour of arrival and total patient volume. METHODS: Retrospective cohort analysis of 109,983 cases from a single academic center. We captured patient disposition, day of week and hour of day of arrival, and total daily volume. Chi-squared test was performed to determine the difference in LWBS rates based on arrival variables. We ran a polynomial regression for LWBS rates by decile of daily patient volume. RESULTS: The overall LWBS rate was 1.82% over 2 years. This varied significantly by day of week and hour of day (p < 0.001). Day of week rates ranged from 0.73% on Sunday to 2.45% on Wednesday. Hour of day rates ranged from 0.26% between 8 AM-9 AM, to 3.71% between 10 PM-11 PM. As total daily patient volume increased, LWBS rates gradually increased until the 70th percentile, followed by significant exponential growth afterwards. DISCUSSION: LWBS rates are not static measurements, and vary greatly depending on ED circumstances. Weekdays and evenings have significantly higher rates. Additionally, LWBS rates climb above 2% as daily registrations reach the 70th percentile, increasing exponentially at each subsequent decile. Understanding these effects will allow for more effective, targeted interventions to minimize this rate and improve throughput.

Researcher degrees of freedom in statistical software contribute to unreliable results: A comparison of nonparametric analyses conducted in SPSS, SAS, Stata, and R.

Researcher degrees of freedom can affect the results of hypothesis tests and consequently, the conclusions drawn from the data. Previous research has documented variability in accuracy, speed, and documentation of output across various statistical software packages. In the current investigation, we conducted Pearson's chi-square test of independence, Spearman's rank-ordered correlation, Kruskal-Wallis one-way analysis of variance, Wilcoxon Mann-Whitney U rank-sum tests, and Wilcoxon signed-rank tests, along with estimates of skewness and kurtosis, on large, medium, and small samples of real and simulated data in SPSS, SAS, Stata, and R and compared the results with those obtained through hand calculation using the raw computational formulas. Multiple inconsistencies were found in the results produced between statistical packages due to algorithmic variation, computational error, and statistical output. The most notable inconsistencies were due to algorithmic variations in the computation of Pearson's chi-square test conducted on 2 × 2 tables, where differences in p-values reported by different software packages ranged from .005 to .162, largely as a function of sample size. We discuss how such inconsistencies may influence the conclusions drawn from the results of statistical analyses depending on the statistical software used, and we urge researchers to analyze their data across multiple packages to check for inconsistencies and report details regarding the statistical procedure used for data analysis.

Pre-Treatment and Post-Treatment Dental Anxiety in Patients Visiting Intern Dental Clinic.

Background and Objectives: This study aimed to assess the dental anxiety of patients using the modified dental anxiety scale (MDAS) questionnaire along with examining the possible relationship between dental anxiety and sociodemographic factors. Materials and Methods: The MDAS questionnaire was used to assess the anxiety level of the patients which included a total of five questions and five options to respond to each question. MDAS questionnaire was filled out by all the patients before the dental treatment. After finishing the treatment, all the patients were given a post-treatment questionnaire to assess their anxiety levels after treatment. Descriptive statistics were performed for measuring the frequency of responses. Mann-Whitney U test was used to compare the anxiety between the gender. The chi-square test was used to identify the distribution of pre-treatment with gender and post-treatment questionnaire with gender and treatment modalities. Linear regression was used to identify the association between clinical variables and different levels of anxiety. Results: A total of 115 patients including 59 males and 56 females with a mean age of 35 ± 11.34 years were included in the current study. Female patients were significantly more anxious about dental treatment compared to male patients. Linear regression showed that age and gender have a significant association with the pre-treatment anxiety level; however, types of treatment is not associated with the MDAS. Anxiety levels decreased for the majority of the patients after the treatment and types of treatment did not show any differences with the post-treatment anxiety level. Conclusions: Age and gender play an important role in dental anxiety; however, types of treatment are not associated with pre-treatment and post-treatment dental anxiety.

Endodontic Procedural Errors and Associated Factors among Undergraduate Dental Students: A Cross-sectional Study.

AIMS AND BACKGROUND: To assess the procedural errors committed by undergraduate students at RAK College of Dental Sciences, during root canal treatments and the factors associated with these errors. MATERIALS AND METHODS: In this cross-sectional study, 180 self-administered questionnaires were distributed, each comprising 26 questions, among 4th and 5th-year students. Participants were requested to report their endodontic mishaps based on feedback from their supervisors. The questionnaire assessed the frequency and types of procedural errors, considering patient, operator, and tooth-related factors. Data were collected tabulated and analyzed using the Chi-square test. RESULTS: A total of 124 root canal-treated teeth exhibiting iatrogenic errors done by students were assessed. Out of which, 53% were performed by 5th-year students, and 69% were conducted by female operators. About 62% of errors occurred in the upper teeth and 68% in the posterior teeth. The most prevalent errors during the rubber dam isolation step were soft tissue trauma (21%) and isolation leakage (20%), significantly associated with limited mouth opening, excessive salivation, and tooth malalignment (p < 0.05). Apical blockage (15%) emerged as the most frequent error during instrumentation phase, showing a significant association with canal dimension and curvature (p < 0.05). For access cavity and obturation phases, under-extended cavity (9%), and under-extended filling (11%) were the most reported errors, respectively. CONCLUSION: Tooth isolation emerges as a particularly challenging aspect for dental students, particularly when dealing with patients exhibiting limited mouth opening and excessive salivation. CLINICAL SIGNIFICANCE: Clinical instructors should caution the undergraduates about the heightened risk of endodontic procedural errors when dealing with patients exhibiting limited mouth opening, excessive salivation, tooth misalignment, and narrow canals. Addressing these challenges is crucial for enhancing the proficiency of undergraduate students in performing successful root canal treatments. How to cite this article: Elsayed MA, Islam MS, Saleh DR, et al. Endodontic Procedural Errors and Associated Factors among Undergraduate Dental Students: A Cross-sectional Study. J Contemp Dent Pract 2023;24(12):998-1007.

Incidence of liver- and non-liver-related outcomes in patients with HCV-cirrhosis after SVR.

BACKGROUND & AIMS: As the long-term benefits of a sustained virological response (SVR) in HCV-related cirrhosis following direct-acting antiviral (DAA) treatment remain undefined, we assessed the incidence and predictors of liver-related events (LREs), non-liver-related events (NLREs) and mortality in DAA-treated patients with cirrhosis. METHODS: Consecutive patients with cirrhosis and SVR were enrolled in a longitudinal, single-center study, and divided into 3 cohorts: Cohort A (Child-Pugh A without a previous LRE), Cohort B (Child-Pugh B or Child-Pugh A with prior non-hepatocellular carcinoma [HCC] LREs), Cohort C (previous HCC). RESULTS: A total of 636 patients with cirrhosis (median 65 years-old, 58% males, 89% Child-Pugh A) were followed for 51 (8-68) months (Cohort A n = 480, Cohort B n = 89, Cohort C n = 67). The 5-year estimated cumulative incidences of LREs were 10.4% in Cohort A vs. 32.0% in Cohort B (HCC 7.7% vs. 19.7%; ascites 1.4% vs. 8.6%; variceal bleeding 1.3% vs. 7.8%; encephalopathy 0 vs. 2.5%) vs. 71% in Cohort C (HCC only) (p <0.0001). The corresponding figures for NLREs were 11.7% in Cohort A vs. 17.9% in Cohort B vs. 17.5% in Cohort C (p = 0.32). The 5-year estimated probabilities of liver-related vs. non-liver-related deaths were 0.5% vs. 4.5% in Cohort A, 16.2% vs. 8.8% in Cohort B and 12.1% vs. 7.7% in Cohort C. The all-cause mortality rate in Cohort A was similar to the rate expected for the general population stratified by age, sex and calendar year according to the Human Mortality Database, while it was significantly higher in Cohort B. CONCLUSIONS: Patients with cirrhosis and an SVR on DAAs face risks of liver-related and non-liver-related events and mortality; however, their incidence is strongly influenced by pre-DAA patient history. LAY SUMMARY: In this large single-center study enrolling patients with hepatitis C virus (HCV)-related cirrhosis cured by direct-acting antivirals, pre-treatment liver disease history strongly influenced long-term outcomes. In patients with HCV-related cirrhosis, hepatocellular carcinoma was the most frequent liver-related complication after viral cure. Due to improved long-term outcomes, patients with cirrhosis after HCV cure are exposed to a significant proportion of non-liver-related events.

Variant PADI3 in Central Centrifugal Cicatricial Alopecia.

BACKGROUND: Central centrifugal cicatricial alopecia (CCCA) is the most common form of scarring alopecia among women of African ancestry. The disease is occasionally observed to affect women in families in a manner that suggests an autosomal dominant trait and usually manifests clinically after intense hair grooming. We sought to determine whether there exists a genetic basis of CCCA and, if so, what it is. METHODS: We used exome sequencing in a group of women with alopecia (discovery set), compared the results with those in a public repository, and applied other filtering criteria to identify candidate genes. We then performed direct sequencing to identify disease-associated DNA variations and RNA sequencing, protein modeling, immunofluorescence staining, immunoblotting, and an enzymatic assay to evaluate the consequences of potential etiologic mutations. We used a replication set that consisted of women with CCCA to confirm the data obtained with the discovery set. RESULTS: In the discovery set, which included 16 patients, we identified one splice site and three heterozygous missense mutations in PADI3 in 5 patients (31%). (The approximate prevalence of the disease is up to 5.6%.) PADI3 encodes peptidyl arginine deiminase, type III (PADI3), an enzyme that post-translationally modifies other proteins that are essential to hair-shaft formation. All three CCCA-associated missense mutations in PADI3 affect highly conserved residues and are predicted to be pathogenic; protein modeling suggests that they result in protein misfolding. These mutations were found to result in reduced PADI3 expression, abnormal intracellular localization of the protein, and decreased enzymatic activity - findings that support their pathogenicity. Immunofluorescence staining showed decreased expression of PADI3 in biopsy samples of scalp skin obtained from patients with CCCA. We then directly sequenced PADI3 in an additional 42 patients (replication set) and observed genetic variants in 9 of them. A post hoc analysis of the combined data sets showed that the prevalence of PADI3 mutation was higher among patients with CCCA than in a control cohort of women of African ancestry (P = 0.002 by the chi-square test; P = 0.006 by Fisher's exact test; and after adjustment for relatedness of persons, P = 0.03 and P = 0.04, respectively). CONCLUSIONS: Mutations in PADI3, which encodes a protein that is essential to proper hair-shaft formation, were associated with CCCA. (Funded by the Ram Family Foundation and others.).

Solid papillary mesothelial tumor.

We report nine examples of a previously undescribed type of peritoneal circumscribed nodular mesothelial tumor characterized by nests or sheets of mesothelial cells with sharp cell borders and extremely bland, sometimes grooved, nuclei. In some cases, nests were separated by fibrous bands. All patients were women, age range 30-72 years (median 52 years). All tumors were incidental findings during surgery and grossly were either solitary nodules or a few small nodules on the peritoneal surface. Referring pathologic diagnoses included diffuse malignant mesothelioma, localized malignant mesothelioma, well-differentiated papillary mesothelioma, and adenomatoid tumor. No tumor showed BAP1 loss by immunohistochemistry nor deletion of CDKN2A by FISH. RNA-seq revealed that these tumors clustered together and were distinct from peritoneal diffuse malignant mesotheliomas. Very few mutations or translocations were found, none of them recurrent from tumor to tumor, and no tumor showed an abnormality in any of the genes typically mutated/deleted in diffuse malignant mesothelioma. Array CGH on three cases revealed two with a completely flat profile and one with a small deletion at 3q26-3q28. On follow-up (range 5-60, median 34 months), there were no deaths, no recurrences, and no evidence of metastatic disease nor local spread; one case that initially had scattered nodules on the pelvic peritoneum had the same pattern of nodules at a second look operation 2 years later. We propose the name solid papillary mesothelial tumor for these lesions. These appear to be either benign or very low-grade tumors that need to be separated from malignant mesotheliomas.

Racial and ethnic disparities in 3-year outcomes following infrainguinal bypass for chronic limb-threatening ischemia.

OBJECTIVE: Black and Hispanic patients have had higher rates of chronic limb-threatening ischemia (CLTI) and experienced worse perioperative outcomes after lower extremity bypass compared with White patients. The underlying reasons for these disparities have remained unclear, and data on 3-year outcomes are limited. Therefore, we examined the differences in 3-year outcomes after open infrainguinal bypass for CLTI stratified by race/ethnicity and explored the potential factors contributing to these differences. METHODS: We identified all CLTI patients who had undergone primary open infrainguinal bypass in the Vascular Quality Initiative registry from 2003 to 2017 with linkage to Medicare claims through 2018 for the 3-year outcomes. Our primary outcomes were the 3-year rates of major amputation, reintervention, and mortality. We also recorded the 30-day major adverse limb events (MALE) defined as major amputation or reintervention. We used Kaplan-Meier estimation methods and multivariable Cox regression analyses to evaluate the outcomes stratified by race/ethnicity and identify contributing factors. RESULTS: Of the 7108 patients with CLTI, 5599 (79%) were non-Hispanic White, 1053 (15%) were Black, 48 (1%) were Asian, and 408 (6%) were Hispanic patients. Compared with White patients, Black patients had higher rates of 3-year major amputation (Black vs White, 32% vs 19%; hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.7-2.2), reintervention (Black vs White, 61% vs 57%; HR, 1.2; 95% CI, 1.1-1.3), and 30-day MALE (Black vs White, 8.1% vs 4.9%; HR, 1.3; 95% CI, 1.2-1.4) but lower mortality (Black vs White, 38% vs 42%; HR, 0.9; 95% CI, 0.8-0.99). Hispanic patients also experienced higher rates of amputation (Hispanic vs White, 27% vs 19%; HR, 1.6; 95% CI, 1.3-2.0), reintervention (Hispanic vs White, 70% vs 57%; HR, 1.4; 95% CI, 1.2-1.6), and MALE (Hispanic vs White, 8.7% vs 4.9%; HR, 1.5; 95% CI, 1.3-1.7. However, mortality was similar between the two groups (Hispanic vs White, 38% vs 42%; HR, 0.88; 95% CI, 0.76-1.0). The low number of Asian patients prevented a meaningful assessment of amputation (Asian vs White, 20% vs 19%; HR, 0.93; 95% CI, 0.44-2.0), reintervention (Asian vs White, 55% vs 57%; HR, 0.79; 95% CI, 0.51-1.2), MALE (Asian vs White, 8.5% vs 4.9%; HR, 0.71; 95% CI, 0.46-1.1), or mortality (Asian vs White, 36% vs 42%; HR, 0.83; 95% CI, 0.52-1.3). In the adjusted analyses, the association of Black race and Hispanic ethnicity with amputation and reintervention was explained by differences in the demographic characteristics (ie, age, sex) and baseline comorbidities (ie, tobacco use, diabetes, renal disease). CONCLUSIONS: Compared with White patients, Black and Hispanic patients had higher 3-year major amputation and reintervention rates. However, mortality was lower for Black patients than for the White patients and similar between Hispanic and White patients. Disparities in amputation and reintervention were partly attributable to differences in demographic characteristics and the higher prevalence of comorbidities in Black and Hispanic patients with CLTI. Future work is necessary to determine whether interventions to improve access to care and reduce the burden of comorbidities in these populations will confer limb salvage benefits.

Surgical site infection after open lower extremity revascularization associated with doubled rate of major limb amputation.

OBJECTIVE: Surgical site infection (SSI) after open lower extremity revascularization is a relatively common complication associated with increased hospital stays, graft infection, and in severe cases, graft loss. Although the short-term effects of SSI can be significant, it has not been considered a complication that increases major limb amputation. The purpose of this study was to determine the association of SSI with outcomes in patients undergoing surgical revascularization for peripheral arterial disease. METHODS: We analyzed nationwide Vascular Quality Initiative (VQI) data from the infrainguinal bypass module from 2003 to 2017. The cohort included adults who underwent open lower extremity bypass for symptomatic peripheral arterial disease and had at least one follow-up record. Weighted Kaplan-Meier curves and Cox proportional hazards regression were used to assess the association between SSI and 1-year mortality and major limb amputation. Inverse-probability of treatment weights were used to account for differences in demographics and patient characteristics and allow for 'adjusted' Kaplan-Meier curves. RESULTS: The analysis included 21,639 patients, and 1155 (5%) had a reported SSI within 30 days of surgery. Patients with SSI were more likely be obese (41% vs 30%), but there were no other clinically relevant differences between demographics, comorbidities, and bypass details. After weighting, patients with SSI were almost twice as likely to undergo major amputation by 6 months (hazard ratio, 1.84; 95% confidence interval, 1.07-3.17). The association with SSI and increased amputation rates persisted at 1 year. The association of SSI on amputation was no different based on preoperative Rutherford class (P = .91). The association between SSI and 1-year mortality rate was not statistically significant (hazard ratio, 1.15; 95% confidence interval, 0.91-1.46). CONCLUSIONS: SSI is more common in obese patients, and patients who develop an SSI are observed to have a significantly increased rate of limb amputation after open lower extremity revascularization.