Back to the Future: How Biology and Technology Could Change the Role of PTFE Grafts in Vascular Access Management

Although the arteriovenous fistula (AVF) is the preferred mode of dialysis vascular access, AVF maturation failure remains a huge clinical problem, often resulting in a prolonged duration of use of tunneled dialysis catheters. In contrast, polytetrafluoroethylene (PTFE) grafts do not suffer from early failure, but have significant problems with later stenosis and thrombosis. This review will initially summarize the pathology and pathogenesis of PTFE graft dysfunction and will then use this as a basis for describing some novel therapies, which may have the potential to reduce PTFE graft dysfunction. Finally, we will emphasize that the introduction of such therapies could be an important first step toward individualizing overall vascular access care.     

Evidence-based protocols for the management of well-differentiated carcinomas of the thyroid

OBJECTIVES: In recent years, well-differentiated carcinomas of the thyroid have been stratified into low-risk and high-risk groups. The pattern of thyroid cancer in India is different from that seen in the West. Moreover, patients present with more advanced stages of the disease. Our aim was to develop protocols for the management of well-differentiated thyroid cancer, based on the analysis of our data and our experience. METHODS: Cases of thyroid carcinoma, which were surgically treated at the Tata Memorial Hospital during 1970-5, were studied. The survival curves were plotted according to the Kaplan-Meier method. Univariate analysis was done using the log rank test. The prognostic factors analyzed were age, sex, tumour size, extra-thyroid extension, distant metastases and lymph node metastases. Multivariate analysis using the Cox regression model was performed. Analyses were separate for follicular and papillary carcinomas. RESULTS: Four hundred and seventeen cases were entered in the study, of which 198 were follicular and 219 were papillary. Based on the evidence derived from this study, we stratified our cases into low- and high-risk groups. The low-risk group consisted of patients below 40 years of age, nodules smaller than 5 cm, absence of extra-thyroidal spread and absence of distant metastases. For follicular carcinoma, the low-risk group had 100% survival at 15 years, compared with 40% for the high-risk group. (p < 0.001). For papillary carcinomas, the survival at 15 years was 95% for the low-risk group and 40% for the high-risk group (p < 0.001). CONCLUSIONS: We recommend lobectomy for the low-risk group, and total thyroidectomy for the high-risk group and for cases with lymph node metastases. In the latter, total thyroidectomy facilitates the use of 131I.     

Current Epidemiology of Revision Total Hip Arthroplasty in the United States: National Inpatient Sample 2009 to 2013

Background

Despite the excellent outcomes associated with primary total hip arthroplasty (THA), implant failure and revision continues to burden the healthcare system. THA failure has evolved and displays variability throughout the literature. In order to understand how THAs are failing and how to reduce this burden, it is essential to assess modes of implant failure on a large scale. Thus, we report: (1) etiologies for revision THA; (2) frequencies of revision THA procedures; (3) patient demographics, payor type, and US Census region of revision THA patients; and (4) the length of stay and total costs based on the type of revision THA procedure.

Accuracy of chitotriosidase activity and CCL18 concentration in assessing type I Gaucher disease severity. A systematic review with meta-analysis of individual participant data

Chitotriosidase activity and CCL18 concentration are interchangeably used for monitoring Gaucher disease (GD) activity, together with clinical assessment. However, comparative studies of these two biomarkers are scarce and of limited sample size. The aim of this systematic review with meta-analysis of individual participant data (IPD) was to compare the accuracy of chitotriosidase activity and CCL18 concentration for assessing type I GD severity. We identified cross-sectional and prospective cohort studies by searching Medline, EMBASE, and CENTRAL from January 1995 to June 2017, and by contacting research groups. The primary outcome was a composite of liver volume >1.25 multiple of normal (MN), spleen volume >5 MN, hemoglobin concentration <11 g/dL, and platelet count <100x109/L. Overall, IPD included 1,109 observations from 334 patients enrolled in nine primary studies, after excluding 111 patients with undocumented values and 18 patients with deficient chitotriosidase activity. IPD were unavailable for 14 eligible primary studies. The primary outcome was associated with a 5.3-fold (95% Confidence Interval [CI]: 4.2-6.6) and 3.0-fold (95% CI: 2.6-3.6) increase of the geometric mean for chitotriosidase activity and CCL18 concentration, respectively. The corresponding areas under the receiver operating characteristics curves were 0.82 and 0.84 (summary difference, 0.02, 95% CI: -0.02 to 0.05). The addition of chitotriosidase activity did not improve the accuracy of the CCL18 concentration. Estimates remained robust in the sensitivity analysis and consistent across subgroups. Neither the chitotriosidase activity nor the CCL18 concentration varied significantly according to a recent history of bone events among 97 patients. In conclusion, the CCL18 concentration is as accurate as chitotriosidase activity in assessing hematological and visceral parameters of GD severity and can be measured in all GD patients. This meta-analysis supports the use of CCL18 rather than chitotriosidase activity for monito-ring GD activity in routine practice.     

Changes in serum lipoprotein profile during interferon therapy in chronic hepatitis C

OBJECTIVES: Therapy with a interferon is associated with a rise in serum triglyceride levels, although this effect has not been well studied with newer forms of interferon or interferon in combination with ribavirin. METHODS: Review of combined data obtained from several prospective, randomized controlled clinical trials conducted in the clinical studies unit of a tertiary care referral center among patients with chronic hepatitis C undergoing treatment with various forms of a interferon, with or without the addition of ribavirin. Serum levels of triglycerides and cholesterol were measured before and during therapy. Changes in these levels were correlated with baseline characteristics. RESULTS: At baseline, the mean serum triglyceride level among 152 patients studied was 130 mg/dL (range 32-620) and was elevated above normal in three patients (2%). During therapy, triglyceride levels rose significantly early on and began to decline spontaneously after 12 wk, returning to baseline after stopping treatment. Triglyceride levels rose above 500 mg/dL in 18 patients (12%) and above 1000 mg/dL in two patients (1.3%) although none experienced acute complications or clinical symptoms. Serum cholesterol levels did not change significantly during therapy (mean at baseline 172 vs 168 mg/dL at 24 wk). Factors correlated with the rise in triglycerides included baseline triglyceride levels, HCV genotype, and the type of interferon used. CONCLUSIONS: Serum triglyceride levels increase consistently in patients with chronic hepatitis C treated with all forms of a interferon, often to very high levels. These changes do not seem to be associated with clinical signs or complications and triglyceride levels decline while patients are still on therapy and return to normal after stopping.     

Mycobacterium tuberculosis “Beijing” epidemics: A race against mutations?

Multi Drug Resistant Tuberculosis Beijing strains exhibit different drug-resistance mutations (DRM) in different locations. By comparing DRM in Beijing reported from Tuberculosis endemic and epidemic locations, we propose that DRM selected in a population cannot tolerate biologically available drugs in different populations resulting in further evolution through novel DRM.     

Targeting stathmin in prostate cancer

Stathmin is the founding member of a family of microtubule-destabilizing proteins that regulate the dynamics of microtubule polymerization and depolymerization. Stathmin is expressed at high levels in a variety of human cancers and provides an attractive molecule to target in cancer therapies that disrupt the mitotic apparatus. We developed replication-deficient bicistronic adenoviral vectors that coexpress green fluorescent protein and ribozymes that target stathmin mRNA. The therapeutic potential of these recombinant adenoviruses was tested in an experimental androgen-independent LNCaP prostate cancer model. Adenovirus-mediated transfer of anti-stathmin ribozymes resulted in efficient transduction and marked inhibition of stathmin expression in these cells. Cells that were transduced with the anti-stathmin adenoviruses showed a dramatic dose-dependent growth inhibition. This was associated with accumulation of LNCaP cells in the G2-M phases of the cell cycle. A similar dose-dependent inhibition of clonogenic potential was also observed in cells infected with anti-stathmin adenoviruses. Morphologic and biochemical analysis of infected cells showed a marked increase in apoptosis characterized by detachment of the cells, increased chromatin condensation, activation of caspase-3, and fragmentation of internucleosomal DNA. If these findings are confirmed in vivo, it may provide an effective approach for the treatment of prostate cancer.