New-Onset Atrial Fibrillation Is a Red Flag to Microvascular Free Tissue Transfer Failure in Head and Neck Cancer Patients.

BACKGROUND: Postoperative new-onset atrial fibrillation (AF) has been shown to be associated with increased surgical morbidity and mortality following cancer ablation surgery. However, evidence of new-onset AF's impact on surgical outcomes in head and neck cancer patients undergoing tumor ablation and microvascular free tissue transfer remains scarce. This study aims to evaluate the association between AF and surgical outcomes in these patients. METHODS: We enrolled head and neck cancer patients who underwent tumor ablation reconstructed with microvascular free tissue transfer from the National Health Insurance Research Database (NHIRD). Patients were grouped into the following: (1) without AF, (2) new-onset AF, and (3) preexisting AF. The groups were matched by propensity score based on age, gender, cancer stage, and comorbidities. The primary outcome was postoperative complications, whereas all-cause mortality was the secondary outcome. RESULTS: In total, 26,817 patients were included in this study. After matching, we identified 2,176 (79.24%) patients without AF, 285 (10.37%) with preexisting AF, and 285 (10.37%) with new-onset AF. Our results demonstrated that the free flap failure rate was twofold escalated in patients with new-onset AF (9.8%) compared to those without AF (5.4%) or preexisting AF (5.3%; p = 0.01). However, we did not identify significant differences among other postoperative complications across groups. Additionally, we found that the risk of all-cause mortality was significantly elevated in patients with preexisting AF (p < 0.001) compared to those without AF or new-onset AF. CONCLUSION: Our study demonstrated that new-onset AF is associated with an increased risk of flap failure and could serve as a predictor. On the other hand, all-cause mortality in patients with preexisting AF was significantly elevated. Close postoperative monitoring in patients with new-onset and preexisting AF is crucial to identify any potential adverse effects.

Risk factors for postoperative adverse airway events in patients with primary oral cancer undergoing reconstruction without prophylactic tracheostomy.

OBJECTIVE: To identify risk factors associated with adverse airway events (AAEs) in primary oral cancer patients undergoing tumor ablation followed by free tissue transfer without prophylactic tracheostomy. METHODS: We retrospectively collected primary oral cancer patients who underwent tumor ablation surgery following free-tissue transfer without prophylactic tracheostomy during February 2017 to June 2019 in Chang Gung Memorial Hospital, Linkou Medical Center, Taiwan. 379 patients were included. Data were analysed from 2020 to 2021. Demographics, comorbidities, intraoperative variables and postoperative respiration profile were obtained from the medical record. Main outcome was postoperative AAEs, including requirement of endotracheal intubation after extubation and tracheostomy after prolonged intubation. RESULTS: Of the 379 patients, postoperative AAEs happened in 29 patients (7.6 %). In reintubation group, patients were older with more diabetes mellitus, hypertension and cerebrovascular disease. These patients had lower preoperative hemoglobin, creatinine, and albumin level with more intraoperative blood transfusion. In postoperative respiration profile, rapid shallow breathing index (RSBI) and PaO2/FiO2 (PF) ratio were poorer. On multivariate analysis, patient's age, tumor location, and cross-midline segmental mandibulectomy and a lower PF ratio were independent risk factors for postoperative AAEs. CONCLUSIONS: In head and neck cancer patients that underwent tumor ablation followed by free tissue transfer without prophylactic tracheostomy, patient's age, tumor location, cross-midline segmental mandibulectomy and P/F ratio are associated with postoperative AAEs.

Surface Modification of Polylactic Acid Bioscaffold Fabricated via 3D Printing for Craniofacial Bone Tissue Engineering.

Bone tissue engineering is a promising solution for advanced bone defect reconstruction after severe trauma. In bone tissue engineering, scaffolds in three-dimensional (3D) structures are crucial components for cell growth, migration, and infiltration. The three-dimensional printing technique is well suited to manufacturing scaffolds since it can fabricate scaffolds with highly complex designs under good internal structural control. In the current study, the 3D printing technique was utilized to produce polylactic acid (PLA) scaffolds. BMSCs were seeded onto selected scaffolds, either hydrogel-mixed or not, and cultivated in vitro to investigate the osteogenic potential in each group. After osteogenic incubation in vitro, BMSC-seeded scaffolds were implanted onto rat cranium defects, and bone regeneration was observed after 12 weeks. Our results demonstrated that BMSCs were able to seed onto 3D-printed PLA scaffolds under high-resolution observation. Real-time PCR analysis showed their osteogenic ability, which could be further improved after BMSCs were mixed with hydrogel. The in vivo study showed significantly increased bone regeneration when rats' cranium defects were implanted with a hydrogel-mixed BMSC-seeded scaffold compared to the control and those without cell or hydrogel groups. This study showed that 3D-printed PLA scaffolds are a feasible option for BMSC cultivation and osteogenic differentiation. After mixing with hydrogel, BMSC-seeded 3D-printed scaffolds can facilitate bone regeneration.

Positive correlation of serum fibroblast growth factor 23 with peripheral arterial stiffness in kidney transplantation patients.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) has a role in arterial stiffness (AS) apart from regulating mineral metabolism. We investigated the association between FGF-23 concentration and peripheral AS in renal transplantation (RT) recipients. METHODS: The fasting blood samples of RT recipients (n = 66) were collected and analyzed. RESULTS: A total of 29 (43.9%) RT recipients were classified under the peripheral AS group. The RT recipients in this group had a higher prevalence of diabetes (P < 0.001), hypertension (P = 0.001), and metabolic syndrome (P = 0.023); longer post-RT duration (P = 0.006); higher systolic blood pressure (P < 0.001) and diastolic blood pressure (P = 0.024); and higher fasting glucose (P = 0.002), total cholesterol (P = 0.049), blood urea nitrogen (P = 0.027), phosphorus (P = 0.047), and FGF-23 concentrations (P = 0.003) and FGF-23/α-klotho ratio (P < 0.001) but lower klotho concentrations (P = 0.025) than those in the control group. Moreover, FGF-23 concentration (adjusted odds ratio: 1.057, 95% confidence interval: 1.011-1.105, P = 0.015) was found to be an independent predictor of peripheral AS in RT recipients. CONCLUSIONS: Serum FGF-23 concentration was a significant predictor of peripheral AS in RT recipients.

Serum leptin level positively correlates with metabolic syndrome among elderly Taiwanese.

OBJECTIVE: Leptin is an adipocyte-derived hormone and has shown positive correlation with obesity and metabolic syndrome (MetS) in many studies. However, there are few studies investigating this relation in elderly people. Therefore, we aimed to investigate the correlation between the fasting serum leptin level and MetS among older Taiwanese. MATERIALS AND METHODS: The fasting serum leptin level was obtained from 62 Taiwanese participants over 65 years old and was measured using a commercially available enzyme immunoassay kit. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. RESULTS: Thirty elderly participants (48.4%) had MetS. The serum leptin level was positively correlated with MetS (P < 0.001). Multivariate logistic regression analysis of the factors significantly associated with MetS showed that logarithmically transformed leptin (log-leptin, each increase 0.1 ng/mL log-leptin, odds ratio: 1.276, 95% confidence interval: 1.015-1.603, P = 0.037) was still an independent predictor of MetS in elderly persons. Univariable linear analysis showed that body weight (r = 0280, P = 0.028), body mass index (r = 0.417, P = 0.001), waist circumference (r = 0.419, P = 0.001), blood urea nitrogen (r = 0255, P = 0.046), log-insulin (r = 0436, P < 0.001), and logarithmically transformed homeostasis model assessment of insulin resistance (r = 0359, P = 0.004) positively correlated with fasting serum log-leptin levels. Multivariate forward stepwise linear regression analysis of the factors significantly associated with fasting serum log-leptin levels revealed that waist circumference (adjusted R2 = 0.083, P = 0.002), statin use (adjusted R2 = 0.058, P = 0.016), and female gender (adjusted R2 = 0.041, P = 0.034) were independent predictors of fasting serum log-leptin levels among elderly participants. CONCLUSION: In elderly Taiwanese, the serum leptin level was positively correlated with MetS. Waist circumference, statin use, and female gender were independent predictors of the fasting serum leptin level in elderly participants.

Hypoadiponectemia is associated with metabolic syndrome in patients with type 2 diabetes.

Adipose tissue-expressed adiponectin levels are inversely related to the degree of adiposity, and a reduction in adiponectin serum levels is accompanied by insulin resistance. The aim of this study was to evaluate the relationship between serum adiponectin concentration and metabolic syndrome (MetS) in patients with type 2 diabetes mellitus (DM). Fasting blood samples were obtained from 150 volunteers with type 2 DM. MetS and its components were defined according to diagnostic criteria from the International Diabetes Federation. Serum adiponectin concentrations were measured using a commercially available enzyme-linked immunosorbent assay. Among the 150 patients with type 2 DM, 102 (68.0%) had MetS. Female gender (P = 0.007), hypertension (P = 0.005), systolic blood pressure (P < 0.001), diastolic blood pressure (DBP, P < 0.001), waist circumference (P < 0.001), body weight (P < 0.001), body mass index (BMI, P < 0.001), fasting glucose (P = 0.035), triglyceride (TG) level (P < 0.001), glycated hemoglobin level (HbA1c, P = 0.020), insulin level (P < 0.001), and homeostasis model assessment of insulin resistance (HOMA-IR, P < 0.001) were higher in DM patients who had MetS, whereas high-density lipoprotein cholesterol (HDL-C) concentrations (P < 0.001) and adiponectin levels (P < 0.001) were lower. Univariate linear analysis revealed that logarithmically transformed age (log-age, r = 0.279; P = 0.001) and HDL-C (r = 0.246; P = 0.002) positively correlated, whereas height (r = -0.183; P = 0.025), body weight (r = -0.282; P < 0.001), BMI (r = -0.237; P = 0.004), waist circumference (r = -0.249; P = 0.002), DBP (r = 0.252; P = 0.002), log-TG (r = 0.255; P = 0.002), log-insulin (r = -0.298; P < 0.001), and log-HOMA-IR (r = 0.288; P < 0.001) negatively correlated with serum adiponectin levels in patients with type 2 DM. Multivariate forward stepwise linear regression analysis revealed that log-age (adjusted R2 change = 0.069; P < 0.001) positively correlated, whereas log-insulin (adjusted R2 change = 0.182; P = 0.002) and HDL-C (adjusted R2 change = 0.037; P = 0.006) negatively correlated with serum adiponectin levels in patients with type 2 DM. This study showed that lower serum adiponectin levels were positively associated with MetS in patients with type 2 DM and significantly positively related to age but negatively related to serum insulin and HDL-C levels in these subjects.

Smoking and severity of hepatic fibrosis in nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Although many predictors of disease severity of nonalcoholic fatty liver disease (NAFLD) have been proposed, studies of the potential effects of specific environmental exposures on human NAFLD are lacking. Smoking increases insulin resistance. Given the pathophysiological role of insulin resistance in NAFLD, characterization of the influence of smoking in NAFLD is warranted. The aim of this paper was to study the potential association between cigarette smoking and advanced fibrosis in NAFLD. METHODS: All adults enrolled in the NASH CRN studies, between October 2004 and February 2008, who had liver biopsies, were included (n=1091). Advanced fibrosis was defined as stages 3-4. Analyses were performed. RESULTS: Significant bivariate associations were demonstrated between advanced fibrosis and age, gender, ethnicity, diabetes, and smoking history. History of smoking ≥ 10 pack-years was more common (p <0.0001) among patients with advanced fibrosis. Multivariate analysis demonstrated an association between smoking history of ≥ 10 pack-years and advanced fibrosis (OR=1.63). Among non-diabetics, history of ≥ 10 pack-years was associated with an OR of 2.48 for advanced fibrosis. High frequencies of advanced fibrosis were observed among diabetics (with or without ≥ 10 pack-years history) and non-diabetics with ≥ 10 pack-years history as compared to non-diabetics without significant smoking history. CONCLUSIONS: Smoking history was associated with advanced liver fibrosis in this large multicenter cohort of NAFLD patients. The results indicate that smoking may enhance the progression of NAFLD partly through its effect on insulin resistance. Our results are consistent with recent animal studies suggesting that cigarette smoke may aggravate fatty liver. To our knowledge, this is the first study to show that cigarette smoking is associated with increased fibrosis severity in human NALFD, suggesting it may accelerate disease progression. These results may support a formal recommendation of smoking cessation in patients with NAFLD.

Prognostic impact of C-REL expression in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) phenotype is believed to confer a better prognosis than DLBCL with an activated B-cell (ABC) phenotype. Previous studies have suggested that nuclear factor-kappaB (NF-kappaB) activation plays an important role in the ABC subtype of DLBCL, whereas c-REL amplification is associated with the GCB subtype. Using immunohistochemical techniques, we examined 68 newly diagnosed de novo DLBCL cases (median follow-up 44 months, range 1 to 142 months) for the expression of c-REL, BCL-6, CD10, and MUM1/IRF4. Forty-four (65%) cases demonstrated positive c-REL nuclear expression. In this cohort of patients, the GCB phenotype was associated with a better overall survival (OS) than the non-GCB phenotype (Kaplan-Meier survival (KMS) analysis, p = 0.016, Breslow-Gehan-Wilcoxon test). In general, c-REL nuclear expression did not correlate with GCB vs. non-GCB phenotype, International Prognostic Index score, or OS. However, cases with a GCB phenotype and negative nuclear c-REL demonstrated better OS than cases with a GCB phenotype and positive nuclear c-REL (KMS analysis, p = 0.045, Breslow-Gehan-Wilcoxon test), whereas in cases with non-GCB phenotype, the expression of c-REL did not significantly impact the prognosis. These results suggest that c-REL nuclear expression may be a prognostic factor in DLBCL and it may improve patient risk stratification in combination with GCB/non-GCB phenotyping.

Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study.

UNLABELLED: Liver biopsy remains the gold standard for diagnosing nonalcoholic steatohepatitis (NASH). We have recently demonstrated that plasma cytokeratin 18 (CK-18) fragment levels correlate with the magnitude of hepatocyte apoptosis and independently predict the presence of NASH. The goal of this study was to validate the use of this biomarker for NASH diagnosis. The study was an ancillary study of the NASH Clinical Research Network (NASH CRN). Our cohort consisted of 139 patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) from eight CRN participant centers across the United States and 150 age-matched healthy controls. CK-18 fragments were measured using a specific enzyme-linked immunosorbent assay. Histology was assessed centrally by study pathologists. CK-18 fragments were markedly increased in patients with NASH versus those without NASH and borderline diagnosis (median [25th, 75th percentile], 335 [196, 511], 194 [151, 270], 200 [148, 284], respectively; P < 0.001). Moreover, the odds of having fibrosis on liver biopsy increased with increasing plasma CK-18 fragment levels (P < 0.001). On multivariate regression analysis, CK-18 fragments remained an independent predictor of NASH after adjusting for variables associated with CK-18 fragments or NASH on univariate analysis (fibrosis, alanine aminotransferase, aspartate aminotransferase, age, biopsy length). The area under the receiver operating characteristic curve for NASH diagnosis was estimated to be 0.83 (0.75, 0.91). CONCLUSION: Determination of CK-18 fragments in the blood predicts histological NASH and severity of disease in a large, diverse population of patients with biopsy-proven NAFLD, supporting the potential usefulness of this test in clinical practice.

Glycogenic hepatopathy: an underrecognized hepatic complication of diabetes mellitus.

Reported are the clinical and pathologic features of glycogenic hepatopathy, a pathologic overloading of hepatocytes with glycogen that is associated with poorly controlled diabetes mellitus. Fourteen cases were studied by stains, including hematoxylin and eosin, trichrome, periodic acid-Schiff, and periodic acid-Schiff with diastase. Ultrastructural analysis was performed in 2 cases. Medical records were reviewed for clinical presentations, laboratory findings, and clinical outcomes. The individuals ranged from 8 to 25 years of age. All had type I diabetes mellitus with poor glycemic control. The clinical presentations included hepatomegaly, abdominal pain, and elevated transaminases (range, 50-1600 IU/L). The transaminases were dramatically elevated in 3 cases to greater than 10 times the upper limit of normal. All biopsies showed diffusely pale staining hepatocytes on hematoxylin and eosin stains, with excessive glycogen accumulation demonstrated by periodic acid-Schiff stains. Ultrastructural examination revealed marked glycogen accumulation in the cytoplasm and nuclei. Most cases showed no evidence for fatty liver disease: steatosis was absent in 12 of 14 cases, simple steatosis was seen in 1 of 14 cases, and mild steatohepatitis was present in 1 of 14 cases. Mallory hyaline was absent in all cases, acidophil bodies were only rarely seen, and inflammation was absent or minimally present. Fibrosis was typically absent, with only 2 cases demonstrating focal mild fibrosis. Three patients had adequate follow-up and demonstrated improvement of liver enzyme levels with control of blood glucose. We conclude that glycogenic hepatopathy can cause hepatomegaly and significant transaminase elevations in individuals with type I diabetes mellitus. The pathology is distinct from steatohepatitis.

Design and validation of a histological scoring system for nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P = .009), hepatocellular ballooning (P = .0001), lobular inflammation (P = .0001), fibrosis (P = .0001), and the absence of lipogranulomas (P = .001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of > or =5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."

Giant insulinoma: case report and review of the literature.

An insulinoma is a rare pancreatic endocrine tumor that is typically sporadic, solitary, and less than 2 cm in diameter. Fewer than 5% of insulinomas are larger than 3 cm. Ninety percent or more of all insulinomas are benign. Larger tumors are more likely to be malignant. We report a case of a giant pedunculated insulinoma, measuring 9 cm in diameter and weighing 100 g, with amyloid deposits accounting for 70% of the tumor volume. At the time of operation, no local invasion or metastatic disease was identified. On pathological evaluation, the tumor was classified as an insulinoma of uncertain biological behavior. In addition to describing the clinical presentation and operative findings, criteria for determining malignancy are outlined, a detailed pathological description is presented, and the 2000 World Health Organization Classification for Pancreatic Endocrine Neoplasms is reviewed.