Mid-treatment Fluorodeoxyglucose Positron Emission Tomography in Human Papillomavirus-related Oropharyngeal Squamous Cell Carcinoma Treated with Primary Radiotherapy: Nodal Metabolic Response Rate can Predict Treatment Outcomes.

AIMS: To evaluate whether biomarkers derived from fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed prior to (prePET) and during the third week (interim PET; iPET) of radiotherapy can predict treatment outcomes in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPC). MATERIALS AND METHODS: This retrospective analysis included 46 patients with newly diagnosed OPC treated with definitive (chemo)radiation and all patients had confirmed positive HPV status (HPV+OPC) based on p16 immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary, index node (node with the highest TLG) and total lymph nodes and their median percentage (≥50%) reductions in iPET were analysed, and correlated with 5-year Kaplan-Meier and multivariable analyses (smoking, T4, N2b-3 and AJCC stage IV), including local failure-free survival, regional failure-free survival, locoregional failure-free survival (LRFFS), distant metastatic failure-free survival (DMFFS), disease-free survival (DFS) and overall survival. RESULTS: There was no association of outcomes with prePET parameters observed on multivariate analysis. A complete metabolic response of primary tumour was seen in 13 patients; the negative predictive value for local failure was 100%. More than a 50% reduction in total nodal MTV provided the best predictor of outcomes, including LRFFS (88% versus 47.1%, P = 0.006, hazard ratio = 0.153) and DFS (78.2% versus 41.2%, P = 0.01, hazard ratio = 0.234). More than a 50% reduction in index node TLG was inversely related to DMFFS: a better nodal response was associated with a higher incidence of distant metastatic failure (66.7% versus 100%, P = 0.009, hazard ratio = 3.0). CONCLUSION: The reduction (≥50%) of volumetric nodal metabolic burden can potentially identify a subgroup of HPV+OPC patients at low risk of locoregional failure but inversely at higher risk of distant metastatic failure and may have a role in individualised adaptive radiotherapy and systemic therapy.

Neoadjuvant Radiotherapy Dose Escalation in Locally Advanced Rectal Cancer: a Systematic Review and Meta-analysis of Modern Treatment Approaches and Outcomes.

AIMS: Improving pathological complete response (pCR) rates after neoadjuvant chemoradiotherapy for locally advanced rectal cancer may facilitate surgery-sparing treatment paradigms. Radiotherapy boost has been linked to higher rates of pCR; however, outcomes in moderately escalated inverse-planning studies have not been systematically evaluated. We therefore carried out a systematic review and meta-analysis of radiation dose-escalation studies in the context of neoadjuvant therapy for locally advanced rectal cancer. MATERIALS AND METHODS: A systematic search of Pubmed, EMBASE and Cochrane databases for synonyms of 'rectal cancer', 'radiotherapy' and 'boost' was carried out. Studies were screened for radiotherapy prescription >54 Gy. Prespecified quality assessment was carried out for meta-analysis inclusion suitability. Pooled estimates of pCR, acute toxicity (grade ≥3) and R0 resection rates were determined with random-effects restricted maximum-likelihood estimation. Heterogeneity was assessed with Higgins I2 and Cochran Q statistic. Subset analysis examined outcomes in modern inverse-planning studies. Meta-regression with permutation correction was carried out for each outcome against radiation dose, radiotherapy technique, boost technique, chemotherapy intensification and other patient- and treatment-related cofactors. RESULTS: Forty-nine primary and three follow-up publications were included in the systematic review. Pooled estimates of pCR, toxicity and R0 resection across 37 eligible publications (n = 1817 patients) were 24.1% (95% confidence interval 21.2-27.4%), 11.2% (95% confidence interval 7.2-17.0%) and 90.7% (95% confidence interval 87.9-93.8%). Within inverse-planning studies (17 publications, n = 959 patients), these rates were 25.7% (95% confidence interval 21.0-31.1%), 9.8% (95% confidence interval 4.6-19.7%) and 95.3% (95% confidence interval 91.6-97.4%). Regression analysis did not identify any significant predictor of pCR (P > 0.05). CONCLUSIONS: Radiotherapy dose escalation above 54 Gy is associated with high rates of pCR and does not seem to increase the risk of acute grade ≥3 toxicity events. pCR rates approaching 25% may be achievable utilising moderate escalation (54-60 Gy) with modern inverse-planning techniques; however, a clear dose-response relationship was not identified in regression analysis and additional evidence is awaited given the prevalence of heterogenous single-arm studies to date.

Endoscopy gender determination and reproductive hormone profiles of Painted Terrapins (Batagur borneoensis) subjected to ex situ incubation.

Chelonian exhibit temperature dependent sex determination, and ex situ incubation of eggs in conservation hatcheries may render a gender bias. The gender of juvenile Painted terrapins (Batagur borneoensis) produced at a conservation hatchery in Malaysia was determined by endoscopy of the gonads. Circulating reproductive hormones (testosterone, progesterone and estradiol) were profiled for 31 juveniles and nine captive-reared non-breeding adult terrapins. Endoscopy revealed a gender bias of 96.8% (30/31) females. Testosterone levels in the juvenile females (2.49 ± 1.29) were significantly lower than that of the adult females (12.20 ± 4.29), and lower than values in the juvenile male (9.36) and adult males (27.60, 35.62). The progesterone levels in the juvenile females (107.12 ± 68.68) were significantly higher than that of the adult females (51.13 ± 24.67), but lower than values in the juvenile male (33.27) and adult males (3.43, 8.51). Estrogen levels were significantly lower in the juvenile females (1.57 ± 1.35) compared to the adult females (77.46 ± 53.45). Negative correlations were observed between levels of progesterone and testosterone, and progesterone and estrogen. A positive correlation was noted between estrogen and testosterone. The present study constitutes the first attempt to determine the gender and reproductive hormone profiles of juvenile Painted terrapins produced by ex situ incubation, and captive non-breeding adults. Endoscopy of the gonads is a useful techniques for gender determination among juvenile turtles, while the use of testosterone as a gender biomarker warrants further investigation.

A Review of Modern Radiation Therapy Dose Escalation in Locally Advanced Head and Neck Cancer.

The management of head and neck cancer is complex and often involves multimodality treatment. Certain groups of patients, such as those with inoperable or advanced disease, are at higher risk of treatment failure and may therefore benefit from radiation therapy dose escalation. This can be difficult to achieve without increasing toxicity. However, the combination of modern treatment techniques and increased research into the use of functional imaging modalities that assist with target delineation allows researchers to push this boundary further. This review aims to summarise modern dose escalation trials to identify the impact on disease outcomes and explore the growing role of functional imaging modalities. Studies experimenting with dose escalation above standard fractionated regimens as outlined in National Comprehensive Cancer Network guidelines using photon therapy were chosen for review. Seventeen papers were considered suitable for inclusion in the review. Eight studies investigated nasopharyngeal cancer, with the remainder treating a range of subsites. Six studies utilised functional imaging modalities for target delineation. Doses as high as 85.9 Gy in 2.6 Gy fractions (EQD2 90.2 Gy10) were reportedly delivered with the aid of functional imaging modalities. Dose escalation in nasopharyngeal cancer resulted in 3-year locoregional control rates of 86.6-100% and overall survival of 82-95.2%. For other mucosal primary tumour sites, 3-year locoregional control reached 68.2-85.9% and 48.4-54% for overall survival. There were no clear trends in acute or late toxicity across studies, regardless of dose or addition of chemotherapy. However, small cohort sizes and short follow-up times may have resulted in under-reporting. This review highlights the future possibilities of radiation therapy dose escalation in head and neck cancer and the potential for improved target delineation with careful patient selection and the assistance of functional imaging modalities.

The first family group of α1-AT-P in the world with repeated hematomas: 10-year follow-up.

This case report describes the first 10-year follow-up report worldwide of a patient with the genetic variation alpha-1-antitrypsin-Pittsburgh mutation (α1-AT-P). The mutation was confirmed in a 16 year-old Chinese girl after she presented with repeated hematomas, and the mutation with bleeding tendency was also verified in her father. α1-AT-P is a spontaneously occurring autosomal dominant point mutation of α1-antitrypsin, in which methionine-358 is substituted by an arginine derivative. α1-AT-P cases are extremely rare, with only eight reported worldwide. Consequently, there is insufficient experience in the diagnosis and treatment of α1-AT-P. We followed up and reviewed the last 10 years of treatment of a young patient who suffered from repeated life-threatening hematomas, underwent emergency surgery five times, and had her ovaries removed in her twenties to avoid ovulation hemorrhage. The purpose of this article is to raise the awareness of α1-AT-P mutation and to improve its prognosis, especially in female patients.

Depression and risk of hip fracture: a systematic review and meta-analysis of cohort studies.

Recently published studies on the association between depression and hip fracture (HF) are inconsistent. Therefore, we performed this meta-analysis with the main aim to clarify the association between depression and HF, and also to identify possible susceptible groups. Relevant literature published until February 2019 was obtained and screened according to established inclusion criteria. Two researchers independently processed quality assessment and data extraction prior to the meta-analysis. Pooled hazard ratios (HRs) with 95%CI (confidence intervals) were calculated. To explore the sources of heterogeneity, subgroup analyses were performed based on study design, study region, NOS scores, follow-up duration, diagnostic criteria, sex, national income level, and adjustments (bone mineral density (BMD), antidepressant, calcium intake, and smoking). Ten studies with 13 estimates, involving 375,438 participants and 4576 HFs, were included. It was found that patients with depression had a higher risk of HF than non-depressed patients (HR = 1.21; 95%CI 1.11-1.31). Sensitivity analysis results show that the association is relatively stable. The studies that were not adjusted for confounders (e.g., antidepressant, BMD, calcium intake, and smoking) had higher overall HR compared to the studies that adjusted for the corresponding confounding factors. HFs are more likely to occur in European and male depression patients. This meta-analysis provided evidence of a modest positive association between depression and the risk of HFs, and the association is stronger in European and male patients. Implementation of practical measures to prevent and treat depression is of great public health significance.

Mycobacterium abscessus: A Rare Cause of Periprosthetic Knee Joint Infection.

A 61-year-old woman with a periprosthetic knee joint infection caused by Mycobacterium abscessus was successfully treated with surgical débridement, multidrug antimicrobial therapy, and staged reimplantation. To the authors' knowledge, this represents the first report of successfully treating this organism after knee arthroplasty. M. abscessus knee infections are rare, and there are no specific guidelines to inform treatment or successful treatment regimens for periprosthetic knee infections. Medical management alone was not successful in this case and hence cannot be recommended. Using a collaborative multidisciplinary approach, including surgical débridement, staged reimplantation, and multidrug antimicrobials, successful eradication of the periprosthetic joint infection caused by M. abscessus was achieved.

Waste-to-biofuel integrated system and its comprehensive techno-economic assessment in wastewater treatment plants.

Combining wastewater treatment and biofuel production is considered the cost-effective way for better waste remediation and lowering the environmental impact for biofuel production. In this study, an innovative integrated system incorporating sludge, scum and centrate treatment and biofuel production was developed. A comprehensive techno-economic analysis was conducted to evaluate the technology and economic feasibility of the integrated system with the consideration of biofuel production, wastewater treatment improvement, tax credits, carbon credit, and coproducts utilization. Benefited from the integrated system that the intermediate byproducts can be used in between the sub-systems, such as the glycerol generated from the scum-to-biodiesel production can be used as an organic carbon for the centrate-to-algae production, the estimated breakeven selling price of the bio-oil ($1.85/gallon) is very close to the 5-year averaged crude oil price. The assessment result showed the payback period and the IRRs of the integrated system are superior in comparison with others.

Correlation analysis of mast cells and EGFR with endoscopic application of tissue glue for treatment of peptic ulcer healing.

OBJECTIVE: To investigate the impact of tissue glue on mast cells (MC) and epidermal growth factor receptor (EGFR) in rat peptic ulcer. MATERIALS AND METHODS: SD rats were used to establish peptic ulcer model. Cimetidine gavage was adopted in the positive control, while cimetidine and endoscopic tissue glue therapy were applied in the experimental group. The ulcer inhibition rate and ulcer index were measured to evaluate healing quality. Real-time PCR was performed to test EGFR mRNA in the ulcer surrounded gastric mucosa. Immunohistochemistry was selected to determine MC quantity. HE staining and apoptosis detection were used to evaluate cell apoptosis. RESULTS: Tissue glue significantly reduced MC number in the peptic ulcer rat compared with control with dose dependence (p < 0.05). Tissue glue significantly decreased ulcer area, and elevated ulcer index and inhibition rate (p < 0.05). EGFR mRNA in the mucosa markedly declined after modeling. Tissue glue upregulated EGFR mRNA to a certain extent (p > 0.05). Tissue glue induced MC apoptosis with dose dependence. CONCLUSIONS: Endoscopic application of tissue glue accelerated ulcer mucosa healing via up-regulating EGFR mRNA, enhancing gastrointestinal mucous membrane regeneration and repair ability, and decreasing MC number.

[Experience of low calcium crisis after the operation in peritonea dialysis secondary].

We report a case of secondary hyperparathyroidism after peritoneal dialysis. After given the total parathyroidectomy and forearm autoplantation (PTX+AT), the patient presented with an acute low calcium crisis (tongue myoparalysis, tetany and ECG abnormalities). As the conventional calcium treatment was invalid, the calcium solution was then changed, and replaced by the standard calcium dialysate with monitoring calcium ions. At the last, the patient was rescued. After a long term followed up, the patient's clinical symptoms were improved, and the parathyroid hormone (iPTH) level basically kept within the scope of the KDIGO guidelines.

[Recent advances in early diagnosis of head and neck cancer in precision medicine era].

Head and neck squamous cell carcinoma, HNSCC, has high morbidity and mortality. Even in America, more than 1/2 to 2/3 patients have been diagnosed at advanced stage. So, it's urgent to find ways to diagnose HNSCC earlier and foresee the curative effect. With the achievement of Next-Generation Sequencing, researchers are trying to develop early diagnostic technology from a new perspective, such as personal genomics, proteomics, metabolomics and other related personal information. Here we reviewed the recent research in early diagnosis of HNSCC.

Prognostic Value of 2-[(18)F] Fluoro-2-deoxy-D-glucose Positron Emission Tomography-Computed Tomography Scan Carried out During and After Radiation Therapy for Head and Neck Cancer Using Visual Therapy Response Interpretation Criteria.

AIMS: To evaluate the prognostic utility of 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography-computed tomography (FDG PET-CT) carried out in the third week (iPET) and after completion (pPET) of definitive radiation therapy in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC) and to investigate the optimal visual grading criteria for therapy response assessment. MATERIALS AND METHODS: Sixty-nine consecutive patients with newly diagnosed MPHNSCC treated with radical radiation therapy with or without systemic therapy underwent staging. PET-CT, iPET and pPET were included. All PET-CT images were reviewed by using a visual grading system to assess metabolic response for primary tumour: 0 = similar to adjacent background blood pool activity; 1 = more than background but < mediastinal blood pool; 2 ≥ mediastinal blood pool and < liver; 3 ≥ liver; and 4 ≥ brain. The results were correlated with locoregional recurrence-free survival (LRFS), disease-free survival (DFS) and overall survival, using Kaplan-Meier analysis. RESULTS: The median follow-up was 28 months (range 6-62), the median age was 61 years (range 39-81) and AJCC 7th edition clinical stage II, III and IV were six, 18 and 45 patients, respectively. The optimal threshold for non-complete metabolic response (non-CMR) was defined as focal uptake ≥ liver (grade 3) for iPET and focal uptake ≥ mediastinum (grade 2) for pPET. The 2 year Kaplan-Meier LRFS, DFS and overall survival estimates for primary CMR and non-CMR in iPET were 89.8% versus 71.5% (P = 0.062), 80.1% versus 65.3% (P = 0.132), 79.1% versus 72.1% (P = 0.328) and in pPET 86.2% versus 44.6% (P = 0.0005), 77.6% versus 41.2% (P = 0.006), 81.2% versus 40.6% (P = 0.01), respectively. The negative predictive value (NPV) for LRFS for patients achieving both primary and nodal CMR in iPET was 100%. No locoregional failure was observed in patients with both primary and nodal iPET CMR (P = 0.038), whereas those with nodal iPET CMR had no regional failure (P = 0.033). However, the positive predictive values (PPV) for LRFS and DFS for iPET and pPET were found to be poor: 30% and 36% for iPET and 35% and 39% for pPET, respectively. CONCLUSION: Standardised criteria using visual assessment are feasible. The metabolic response using visual assessment with standardised interpretation criteria of iPET and pPET can be useful predictors of tumour control. Dose de-escalation can be considered on the basis of a high NPV for iPET. However, the PPV of iPET is poor, indicating that additional discriminative tools are needed.

Impact of a Palliative Care Program on Tracheostomy Utilization in a Community Hospital.

BACKGROUND: Tracheostomies are typically provided to wean patients off the ventilator. However, in many circumstances tracheostomies are placed in patients who are at the end of their life with little hope of meaningful recovery. Palliative care teams decrease utilization of aggressive medical interventions in patients who are at the end of life. OBJECTIVE: The study objective was to determine the impact of a palliative care team on tracheostomy utilization in a community hospital setting. METHODS: The study was a four-year retrospective analysis of adult patients undergoing elective tracheostomy two years before and after the establishment of a palliative care program. The study in an ethnically diverse community hospital included patients older than 18 years old, with patients undergoing a tracheostomy due to trauma excluded. Before and after comparisons were made of demographics, in-hospital mortality, length of stay, and discharge status of patients undergoing tracheostomy. RESULTS: Seven hundred ninety patients undergoing tracheostomy were identified (n = 406, n = 384 before and after September 10, 2010, respectively). Patients were ethnically diverse (Caucasian 43%, Asian 23%, African American 11%, Hispanic 7%). The number of hospital admissions slightly increased during these two time periods (n = 58,926; n = 60,662, respectively). There were no statistical differences in age (73 versus 72, p = 0.827); gender (n = 218 [54%] versus n = 217 [57%] male, p = 0.426); or race (n = 187 [46%] versus n = 150 [39%] Caucasian, p = 0.073) in the two time periods. Patients who underwent tracheostomy after a palliative care service was established had less incidence of comorbid disease (Charlson Comorbidity Index score [CCIS]: 2 versus 3, p = 0.025); lower inpatient mortality (n = 107 [28%] versus n = 148 [37%], p = 0.009]); greater discharge to home or rehabilitation (n = 262 [68%] versus n = 249 [62%], p = 0.01); and lower rates of palliative weaning from mechanical ventilation (n = 61[16%] versus n = 113 [28%], p < 0.001). CONCLUSIONS: In an ethnically diverse community hospital, the institution of a palliative care program appears to have improved patient selection for tracheostomy with lower rates of inpatient mortality, improved rates of home discharge, and lower rates of palliative weaning from mechanical ventilation.

Role of endothelin-1 in the skin fibrosis of systemic sclerosis.

Endothelin-1 (ET-1) acts as a key regulator of vasoconstriction and fibrosis. Many previous studies have focused on the role of ET-1 in scleroderma (systemic sclerosis, SSc). We investigated the effects of ET-1 on the production of extracellular matrix in SSc and normal skin fibroblasts. Primary cultured dermal fibroblasts from SSc patients and healthy controls were treated with ET-1 (25 ng/mL) for 0 min, 15 min, 1 h, 24 h, 48 h and 72 h, respectively. Our results showed that, in SSc fibroblasts, ET-1 upregulated collagen type I, connective tissue growth factor (CTGF), type I plasminogen activator inhibitor (PAI-1) and pAkt in a time-dependent manner within 72 h; in normal fibroblasts, 25 ng/mL ET-1 stimulation correlated with high levels of CTGF, PAI-1 and pAkt. The secretion of fibronectin (FN), collagen type I, and PAI-1 is markedly increased in the supernatant of both SSc fibroblasts and normal fibroblasts. Furthermore, ET-1 phosphorylates Smad2 and Smad3 in normal fibroblasts, but not in SSc fibroblasts. In conclusion, our results demonstrated that ET-1 may induce fibrosis in dermal fibroblasts through Akt signals.

Allopurinol enhanced thiopurine treatment for inflammatory bowel disease: safety considerations and guidelines for use.

WHAT IS KNOWN AND OBJECTIVE: The thiopurine medications are standard inflammatory bowel disease treatments. Therapeutic failure is observed, however, often because of variable drug metabolism. Allopurinol can enhance the potency of thiopurine treatment. Our objective is to review the relevant literature, and our own experience, to determine if allopurinol enhancement of thiopurine treatment is a reasonable therapeutic strategy. COMMENT: Published reports of, and our own experience using, allopurinol-thiopurine combination therapy indicate that the addition of allopurinol will enhance thiopurine treatment in up to 60% of patients. There are risks to this approach, but with appropriate monitoring, these risks should approximate those observed with thiopurine therapy alone. WHAT IS NEW AND CONCLUSION: Combination therapy with allopurinol and a thiopurine is a reasonable alternative for inflammatory bowel disease patients not responding to thiopurine monotherapy. Physicians experienced in thiopurine treatment, who have familiarity with thiopurine metabolism, and are willing to engage in appropriate therapeutic monitoring, should consider this strategy.

Development and regeneration of Sox2+ endoderm progenitors are regulated by a Hdac1/2-Bmp4/Rb1 regulatory pathway.

The mechanisms that govern the maintenance and differentiation of tissue-specific progenitors in development and tissue regeneration are poorly understood. We show that development of Sox2+ progenitors in the lung endoderm is regulated by histone deacetylases 1 and 2 (Hdac1/2). Hdac1/2 deficiency leads to a loss of Sox2 expression and a block in proximal airway development. This is mediated in part by derepression of Bmp4 and the tumor suppressor Rb1, which are direct transcriptional targets of Hdac1/2. In contrast to development, postnatal loss of Hdac1/2 in airway epithelium does not affect the expression of Sox2 or Bmp4. However, postnatal loss of Hdac1/2 leads to increased expression of the cell-cycle regulators Rb1, p21/Cdkn1a, and p16/Ink4a, resulting in a loss of cell-cycle progression and defective regeneration of Sox2+ lung epithelium. Thus, Hdac1/2 have both common and unique targets that differentially regulate tissue-specific progenitor activity during development and regeneration.

Akt1 deficiency modulates reward learning and reward prediction error in mice.

In contemporary reinforcement learning models, reward prediction error (RPE), the difference between the expected and actual reward, is thought to guide action value learning through the firing activity of dopaminergic neurons. Given the importance of dopamine in reward learning and the involvement of Akt1 in dopamine-dependent behaviors, the aim of this study was to investigate whether Akt1 deficiency modulates reward learning and the magnitude of RPE using Akt1 mutant mice as a model. In comparison to wild-type littermate controls, the expression of Akt1 proteins in mouse brains occurred in a gene-dosage-dependent manner and Akt1 heterozygous (HET) mice exhibited impaired striatal Akt1 activity under methamphetamine challenge. No genotypic difference was found in the basal levels of dopamine and its metabolites. In a series of reward-related learning tasks, HET mice displayed a relatively efficient method of updating reward information from the environment during the acquisition phase of the two natural reward tasks and in the reverse section of the dynamic foraging T-maze but not in methamphetamine-induced or aversive-related reward learning. The implementation of a standard reinforcement learning model and the Bayesian hierarchical parameter estimation show that HET mice have higher RPE magnitudes and that their action values are updated more rapidly among all three test sections in T-maze. These results indicate that Akt1 deficiency modulates natural reward learning and RPE. This study showed a promising avenue for investigating RPE in mutant mice and provided evidence for the potential link from genetic deficiency, to neurobiological abnormalities, to impairment in higher-order cognitive functioning.

The role of hepatic liver X receptor α- and sterol regulatory element binding protein-1c-mediated lipid disorder in the pathogenesis of non-alcoholic steatohepatitis in rats.

Liver X receptor α (LXRα) and sterol regulatory element binding protein-1c (SREBP-1c) were studied in rats with non-alcoholic steatohepatitis (NASH) induced by a high-fat diet. Forty 5-week-old rats were fed either a high-fat diet (n = 30) or a normal diet (n = 10) for 9, 13 or 17 weeks. The mRNA and protein levels for LXRα and SREBP-1c were measured at each time point, as was fatty acid synthase (FAS) activity and the serum levels of free fatty acid (FFA) and triglyceride (TG). The mRNA and protein levels for LXRα and SREBP-1c, FAS activity and serum levels of FFA and TG all significantly increased from week 9 in the high-fat diet rats versus controls. In conclusion, a high-fat diet upregulates LXRα which, in turn, upregulates SREBP-1c, increasing the activity of FAS and FFA and accumulation of TG in hepatocytes. Thus, LXRα and SREBP-1c contribute to the development of NASH.

CT assessment of tracheobronchial anomaly in left pulmonary artery sling.

BACKGROUND: The left pulmonary artery sling (LPAS) is a rare vascular anomaly where the left pulmonary artery arises from the right pulmonary artery, passes over the right bronchus, and goes posteriorly between the trachea and esophagus. The LPAS is frequently associated with cardiac and non-cardiac defects including tracheobronchial abnormalities. OBJECTIVE: To evaluate the utility of multislice CT (MSCT) and helical CT (HCT) in diagnosing and defining the tracheobronchial anomaly and anatomic relationships between the trachea and aberrant left pulmonary artery. MATERIALS AND METHODS: MSCT or HCT was performed in 27 children to determine the tracheobronchial anatomy and identify tracheobronchial stenosis. Eighteen children underwent surgery. RESULTS: According to the Wells classification of LPAS, which includes two main types and two subtypes, there were eight cases of type 1A, five cases of type 1B, six cases of type 2A and eight cases of type 2B in this group. Twenty-four of the 27 children had substantial tracheobronchial stenosis. Four died before surgery; the 18 had reanastomosis of the left pulmonary artery. Five children also had tracheoplasty; three died after surgery. CONCLUSION: CT, especially MSCT, is an ideal modality for simultaneously identifying aberrant left pulmonary artery and any associated tracheobronchial anomaly. The Wells classification is useful for operative planning.

A case of Mollitias and Fragilitas Ossium - unusual presentation of hairy cell leukaemia followed by the diagnosis of nonsecretory myeloma.

Hairy cell leukaemia (HCL) is a B-cell malignancy with a late developmental arrest. This report describes a patient that presented with leucocytosis and splenomegaly. The abnormal leucocytes showed typical morphology and expressed CD103, CD11c, CD19 and CD20 but not CD25 by immunophenotyping. The patient failed to respond to splenectomy and then developed lytic bone lesions and pathological fractures, which progressed despite a single course of cladribine chemotherapy. Review of the pathology of the bone reamings showed nonsecretory myeloma of the same kappa-light chain isotype. He went on to receive induction chemotherapy in preparation for an autologous stem-cell transplant but failed to mobilize sufficient numbers of stem cells. He has had two localized relapses with bony lesions, one within 6 weeks of stopping chemotherapy for which he received localized radiotherapy and thalidomide consolidation. Sequential myeloma has been described in HCL. There is controversy whether this represents clonal evolution or a secondary malignancy. An increased rate of secondary malignancies has been reported by some, but not other, authors in long-term survivors of HCL. This case illustrates the value of a repeat pathological review in case of unexpected complications.