Validation of the UICC 8th edition staging of oral cavity squamous cell carcinoma in a UK cohort.

The eighth edition of the Union for International Cancer Control (UICC) staging manual was recently introduced. The staging of oral cavity squamous cell carcinoma saw changes in relation to depth of invasion and extra-nodal extension. We aimed to evaluate this system and its prognostic ability in a UK cohort. A retrospective review was undertaken of patients diagnosed with squamous cell carcinoma (SCC) of the oral cavity between January 2009 and December 2013. Data were collected on demographics, histology, and recurrence-free (RFS) and five-year overall survival (OS). Patients were staged using both the seventh and eighth editions of the UICC staging manual. Stage-specific survival analysis was performed using the Kaplan-Meier method. A total of 191 records were reviewed and 87 were included in the analysis. The mean (range) age was 60 (37-88) years, and 53% were male. The tongue was the most common site (51%). Using the seventh edition patients were staged as stage I=30, II=14, III=7, IVa=35, and IVb=1. Applying the eighth edition, 26 patients (30%) were upstaged (I=24, II=15, III=14, IVa=17, IVb=17). Ten were upstaged based on pT and 16 on pN status. Both staging manuals showed statistically significant discrimination between stages for both OS and RFS. Patients upstaged from stage IVa in the seventh edition had significantly worse OS in the new system (p=0.043). Both staging systems discriminated accurately between stages. Patients upstaged in stage IVa showed significantly worse OS suggesting improved prognostication with the eighth edition and the changes introduced.

Prevalence of undiagnosed atrial fibrillation in elderly individuals and potential cost-effectiveness of non-invasive ambulatory electrocardiographic screening: The ASSERT-III study.

BACKGROUND: In approximately 10% of patients with implanted pacemakers or defibrillators, previously unrecognized atrial fibrillation (AF) is detected within 3 months. It is unknown whether elderly patients without implanted devices have a similar prevalence of undiagnosed AF using non-invasive ECG monitoring, and if this approach to screening in this population is cost-effective. METHODS: Individuals ≥80 years old attending outpatient clinics without a history of AF and with hypertension and one additional risk factor underwent 30 days of continuous ECG monitoring with an option for an additional 30 days of monitoring if no AF was detected. The primary outcome was AF ≥ 6 min. Cost-effectiveness to prevent stroke was estimated using a Markov model based on observed AF detection rates and data from the published literature. RESULTS: Among 129 patients enrolled, 100 initiated monitoring for an average duration of 36 ±â€¯21 days. The proportion of patients that completed at least 30 days of monitoring was 59%. Average age was 84 ±â€¯3 years and mean CHA2DS2-VASc score was 4.5 ±â€¯1.2. AF ≥ 6 min was documented in 14%, ≥6 h in 8%, and ≥24 h in 3%. One week of monitoring costed $50,000 per quality-adjusted life-year-gained, 30 days and 60 days of monitoring costed $70,000 and $84,000, respectively. CONCLUSIONS: Continuous non-invasive ECG monitoring is feasible in elderly patients. Undiagnosed AF is present in many elderly individuals, with 1 in 7 having episodes lasting ≥6 min. One week of monitoring may be cost-effective for stroke prevention in this population.

Serum fluoride and sialic acid levels in osteosarcoma.

Osteosarcoma is a rare malignant bone tumor most commonly occurring in children and young adults presenting with painful swelling. Various etiological factors for osteosarcoma are ionizing radiation, family history of bone disorders and cancer, chemicals (fluoride, beryllium, and vinyl chloride), and viruses. Status of fluoride levels in serum of osteosarcoma is still not clear. Recent reports have indicated that there is a link between fluoride exposure and osteosarcoma. Glycoproteins and glycosaminoglycans are an integral part of bone and prolonged exposure to fluoride for long duration has been shown to cause degradation of collagen and ground substance in bones. The present study was planned to analyze serum fluoride, sialic acid, calcium, phosphorus, and alkaline phosphatase levels in 25 patients of osteosarcoma and age- and sex-matched subjects with bone-forming tumours other than osteosarcoma and musculo-skeletal pain (controls, 25 each). Fluoride levels were analyzed by ISE and sialic acid was analyzed by Warren's method. Mean serum fluoride concentration was found to be significantly higher in patients with osteosarcoma as compared to the other two groups. The mean value of flouride in patients with other bone-forming tumors was approximately 50% of the group of osteosarcoma; however, it was significantly higher when compared with patients of group I. Serum sialic acid concentration was found to be significantly raised in patients with osteosarcoma as well as in the group with other bone-forming tumors as compared to the group of controls. There was, however, no significant difference in the group of patients of osteosarcoma when compared with group of patients with other bone-forming tumors. These results showing higher level of fluoride with osteosarcoma compared to others suggesting a role of fluoride in the disease.

Warfarin use and the risk of valvular calcification.

BACKGROUND: Warfarin affects the synthesis and function of the matrix Gla-protein, a vitamin K-dependent protein, which is a potent inhibitor of tissue calcification. OBJECTIVES: To investigate the incidence of mitral valve calcium (MVC), mitral annular calcium (MAC) and aortic valve calcium (AVC) in patients with non-valvular atrial fibrillation (AF) treated with warfarin vs. no warfarin. PATIENTS AND METHODS: Of 1155 patients, mean age 74 years, with AF, 725 (63%) were treated with warfarin and 430 (37%) without warfarin. The incidence of MVC, MAC and AVC was investigated in these 1155 patients with two-dimensional echocardiograms. Unadjusted logistic regression analysis was conducted to examine the association between the use of warfarin and the incidence of MVC, MAC or AVC. Logistic regression analyses were also conducted to investigate whether the relationship stands after adjustment for confounding risk factors such as age, sex, race, ejection fraction, smoking, hypertension, diabetes, dyslipidemia, coronary artery disease (CAD), glomerular filtration rate, calcium, phosphorus, calcium-phosphorus product, alkaline phosphatase, use of aspirin, beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins. RESULTS: There was a significant association between the use of warfarin and the risk of calcification [unadjusted odds ratio = 1.71, 95% CI = (1.34-2.18)]. The association still stands after adjustment for confounding risk factors. MVC, MAC or AVC was present in 473 of 725 patients (65%) on warfarin vs. 225 of 430 patients (52%) not on warfarin (P < 0.0001). Whether this is a causal relationship remains unknown. CONCLUSIONS: Use of warfarin in patients with AF is associated with an increased prevalence of MVC, MAC or AVC.

Assessment of platelet inhibition secondary to clopidogrel and aspirin therapy in preoperative acute surgical patients measured by Thrombelastography Platelet Mapping.

BACKGROUND: Increasing numbers of patients prescribed clopidogrel and aspirin are presenting for non-elective surgery. No consensus on the timing of surgery exists after withdrawal of antiplatelet and tests of platelet function are not routinely available. The Thrombelastography Platelet Mapping (TEG-PM) assay is designed to assess platelet inhibition secondary to antiplatelet therapy. We assessed its ability to detect platelet inhibition in preoperative acute surgical patients. METHODS: We conducted a prospective observational study in three groups of preoperative patients: those taking clopidogrel or aspirin up to admission, and a control group. TEG-PM was performed on the day of admission and alternate days until surgery. RESULTS: Mean (SD) platelet thromboxane A(2) receptor inhibition in the control group was 17.5% (23.8) (n=20), 52.6% (32.3) (n=18) in the aspirin group, and 31.9% (27.6) (n=21) in the clopidogrel group (P<0.01). Mean (SD) platelet adenosine diphosphate (ADP) receptor inhibition in the control group was 47.8% (18.9) (n=20), 52.6% (19.7) (n=18) in the aspirin group, and 71.5% (18.4) (n=21) in the clopidogrel group (P<0.01). Among the clopidogrel group awaiting surgery, mean platelet ADP channel inhibition decreased on day 3 to 67.1% (24.7) (n=11), 48.8% (24.4) (n=4) on day 5, and 36.1% (15.9) (n=2) on day 7 (P=0.57). CONCLUSIONS: TEG-PM can identify statistically significant platelet inhibition after antiplatelet therapy; however, the overlap in platelet receptor inhibition between the three groups is likely to limit the clinical usefulness of this test.

Pulsatile ocular blood flow in asymmetric age-related macular degeneration.

PURPOSE: Ocular perfusion abnormalities have been proposed in the pathogenesis of age-related macular degeneration (AMD) with differences in pulsatile ocular blood flow (POBF) in eyes with asymmetric AMD in Japanese and Taiwanese patients. The purpose of our study was to observe POBF difference in the fellow eyes of Caucasians with asymmetric AMD. METHODS: This was a cross-sectional study comparing POBF in three groups of patients with asymmetric AMD in the fellow eyes: Group 1 (n=21) with drusen and active choroidal neovascularisation (CNV); Group 2 (n=18) with drusen and disciform scar; Group 3 (n=8) with CNV and disciform scar. The POBF was adjusted for intraocular pressure (IOP), pulse rate (PR), and axial length using multiple regression analysis. Generalised estimation equation model was used to include both eyes in each group. RESULTS: The geometric mean (95% confidence interval) POBF values were as follows: Group 1 with drusen 1097.9 microl/min (957.0, 1259.7) in one eye and the fellow eye with CNV 1090.1 microl/min (932.3, 1274.7); Group 2 with drusen 946.0 microl/min (794.2, 1126.7) and disciform scar 966.2 microll/min (780.3, 1196.4); Group 3 with CNV 877.1 microl/min (628.3, 1224.6) and disciform scar 767.2 microl/min (530.5, 1109.7). Adjusting for differences in axial length, pulse rate and intraocular pressure, no statistically significant difference in POBF was found between fellow eyes in the same subject. CONCLUSIONS: POBF is not different between fellow eyes of Caucasian patients with asymmetric AMD.

Accessibility and quality of secondary care rheumatology services for people with inflammatory arthritis: a regional survey.

Secondary care rheumatology services for patients with inflammatory arthritis (IA) in the West Midlands were audited using Arthritis and Musculoskeletal Alliance (ARMA) standards of care. Questionnaires were analysed from 1,715 patients in 11 rheumatology departments. ARMA standards recommend full multidisciplinary team assessment; referral rates to nurse specialists (52.3%), physiotherapists (48.7%) and occupational therapists (36.5%) were, however, lower than expected. Attendance at existing hospital-led education groups was rare (8.9%), awareness of existing helplines was moderate (59.2%) but the proportion of patients reporting satisfaction with advice about their disease was high (80.5%). Significant variations were found between departments. For patients with IA < 2 years (n = 236), 84.5% were seen by a rheumatologist within the ARMA standard of 12 weeks of referral; diagnosis of a type of IA was made at the first rheumatology appointment in 66.4%; 82.8% of rheumatoid arthritis patients had commenced disease-modifying drugs, although time to commencement varied across departments. This study raises issues regarding provision of rheumatology services, prioritisation of patient referral and patient education.

The impact of anti-tumour necrosis factor therapy for rheumatoid arthritis on the use of other drugs and hospital resources in a pragmatic setting.

BACKGROUND: Anti-tumour necrosis factor (anti-TNF) therapy has been an important development for the treatment of rheumatoid arthritis (RA) but the impact of its delivery on hospital resources in still emerging. AIMS: We audited the effect of starting anti-TNF on the use of other anti-rheumatic therapies and hospital resources in a routine secondary care setting. METHODS: A retrospective study of resource use before and after anti-TNF was conducted. Hospital records of 54 RA patients were studied and data taken from the time of commencing anti-TNF to 1 October 2004 and an equal time period prior to commencing anti-TNF. Identical data were collected for 54 controls not on anti-TNF. Relevant figures were extrapolated to per annum rates. Results were analysed using two-factor ANOVAs comparing the pre- versus post-anti-TNF period. Cases on intravenous (IV) versus subcutaneous (SC) anti-TNF were also compared in separate ANOVAs. RESULTS: Mean duration of anti-TNF therapy was 17.04 months (range 3.60-42.36). Mean pre- and 3-months post-anti-TNF Disease Activity Scores (DAS28) were 6.93 and 3.88, respectively. Cases were more likely than controls to be on oral prednisolone pre- and post-anti-TNF. Methylprednisolone requirement, number of disease-modifying anti-rheumatic drugs (DMARDs), telephone helpline contacts and duration as an inpatient reduced significantly post-anti-TNF. Day case admissions increased but outpatient appointments decreased only in cases on IV anti-TNF. CONCLUSIONS: In a pragmatic setting, anti-TNF therapy led to reduced need for steroid injections and other DMARDs, as well as reductions in use of several hospital resources. Wider replication of these findings will be important for planning delivery.

Dall-Miles cable and plate fixation system in the treatment of periprosthetic femoral fractures: a review of 20 cases.

PURPOSE: To assess the effectiveness of Dall-Miles cables and plates in the treatment of periprosthetic femoral fractures around hip arthroplasties. METHODS: We retrospectively reviewed 20 cases of periprosthetic femoral fracture treated with the Dall-Miles cable and plate system between November 1999 and December 2002 in James Paget Hospital in the United Kingdom. Demographic data, fracture type, and surgical outcome of the patients were reviewed and assessed. RESULTS: Of the 20 cases of periprosthetic femoral fracture, one was of Vancouver type A, 15 were of type B1, and 4 were of type C. The mean age at operation was 78.5 years (range, 68-90 years) with a male to female ratio of 11:9. The mean time to union was 3.9 months (range, 3-8 months), and the mean follow-up period was 19.4 months (range, 1-4 years). 15 patients achieved satisfactory results, including 2 delayed unions that healed with a residual varus deformity of 15 degrees in the femoral component. Three patients developed deep-seated wound infections. No nonunion of fractures or fixation system failures occurred. CONCLUSION: The Dall-Miles cable and plate fixation system alone is a sufficient treatment for most periprosthetic femoral fractures. In the management of B1 fractures, there was no significant difference in clinical outcome, despite the various combinations of cables and screws used for stabilisation of the plate. However, in cases of comminution at the fracture site, junctional grafting with morsellised autograft may be used in addition to internal fixation to accelerate union.

Cell-based gene transfer of vascular endothelial growth factor attenuates monocrotaline-induced pulmonary hypertension.

BACKGROUND: Pulmonary arterial hypertension is characterized by increased pulmonary vascular resistance secondary to a decrease in the caliber and number of pulmonary vascular channels. We hypothesized that the targeted overexpression of an angiogenic factor within the lung would potentially minimize the development and progression of pulmonary arterial hypertension by preventing the loss of existing vessels or by inducing the development of new blood vessels within the lung. METHODS AND RESULTS: We used a cell-based method of gene transfer to the pulmonary microvasculature by delivering syngeneic smooth muscle cells overexpressing vascular endothelial growth factor (VEGF)-A to inbred Fisher 344 rats in which pulmonary hypertension was induced with the pulmonary endothelial toxin monocrotaline. Four weeks after simultaneous endothelial injury and cell-based gene transfer, right ventricular (RV) hypertension and RV and vascular hypertrophy were significantly decreased in the VEGF-treated animals. Four weeks after gene transfer, the plasmid VEGF transcript was still detectable in the pulmonary tissue of animals injected with VEGF-transfected cells, demonstrating survival of the transfected cells and persistent transgene expression. In addition, delay of cell-based gene transfer until after the development of pulmonary hypertension also resulted in a significant decrease in the progression of RV hypertension and hypertrophy. CONCLUSIONS: These results indicate that cell-based VEGF gene transfer is an effective method of preventing the development and progression of pulmonary hypertension in the monocrotaline model and suggest a potential therapeutic role for angiogenic factors in the therapy of this devastating disease.

The effects of hemodilution with Hemolink upon hemodynamics and blood flow distribution in anesthetized dogs.

Hemoglobin based oxygen-carrying solutions (HBOCs) as hemoglobin replacement therapeutics are being tested for clinical use. Some of these products are associated with elevations in both systemic and pulmonary vascular resistances but their effect on the distribution of blood flow to major organs in larger animals have not been extensively described. We tested two formulations of o-raffinose cross-linked human hemoglobin, Hemolink (frozen Hemolink-1 and refrigerated Hemolink-2) and compared them to Pentaspan, a colloid volume expander in extensive clinical use. Cardiovascular measurements and the distribution of blood flow (radionuclide-labeled microspheres) to the major organs were determined in Beagle dogs (n=5 per group). After baseline measurements, either Hemolink-1, or Hemolink-2, or Pentaspan was exchange transfused in an isovolemic manner (resulting in hematocrit reduction to approximately 20-25%); measurements were made 30, 60, 120 and 180 min post-exchange. There was no significant difference in cardiac output, mean arterial pressures and systemic or pulmonary vascular resistance after exchange in any of the three groups. Myocardial blood flow increased in all three groups post-exchange but the increase was more sustained in the Hemolink groups. Endocardial/epicardial flow ratios were also maintained after exchange in all groups. Thus, Hemolink is ideally suited for volume replacement when used in conjunction with acute normovolemic hemodilution because under these circumstances, the adverse hemodynamic effects are alleviated while extra hemoglobin is added to the blood.

Measurement of endotracheal tube cuff leak to predict postextubation stridor and need for reintubation.

BACKGROUND: The purpose of this study was to determine the predictive value of an endotracheal tube cuff leak for the development of postextubation stridor and the need for reintubation. STUDY DESIGN: Consecutive trauma patients who required intubation at a level I trauma center from July 1997 to July 1998 were studied prospectively. Pediatric patients and those who did not meet the standard weaning protocol criteria established by the Division of Trauma and Surgical Critical Care were excluded. Injury Severity Score, endotracheal tube size, reason for intubation, and the number of days intubated before the initial extubation attempt were recorded. At the time of extubation, the difference in exhaled tidal volume from before to after endotracheal tube cuff deflation was calculated. This number was then divided by the exhaled tidal volume before cuff deflation and was recorded as the percent cuff leak. Patients were followed for 24 hours after extubation for the development of stridor or need for reintubation. Statistical analysis to compare subgroups of patients was performed using ANOVA with Scheffé post hoc analysis. RESULTS: Among the 110 patients analyzed, the most common reason for intubation was closed-head injury. Seven patients (6.4%) developed stridor alone and had a mean cuff leak of 5 8 mL (8.4% of tidal volume before cuff deflation). Six patients (5.5%) experienced stridor that required reintubation and had a mean cuff leak of 68 mL (9.2% of tidal volume before cuff deflation). Patients who developed stridor or needed reintubation had been intubated for a significantly greater length of time than those not developing stridor or requiring reintubation (2.6 versus 3.0 days, p < 0.001). There were no differences in Injury Severity Score, endotracheal tube size, or reason for intubation between these groups. CONCLUSIONS: A cuff leak of less than 10% of tidal volume before cuff deflation is useful in identifying patients at risk for stridor or reintubation (96% specificity). It appears that the amount of cuff leak decreases after intubation for more than 3 days, increasing the risk of stridor and need for reintubation. This information may be helpful in identifying those patients who need treatment for laryngotracheal edema, ie, use of steroids or anesthesia during extubation, the efficacy of which remains to be determined.