Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab

Background Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.Methods Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models.Results Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42–0.93)], LRC [HR (95% CI) = 0.56 (0.37–0.86)] and OS [HR (95% CI) = 0.63 (0.43–0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37–0.82), LRC:HR (95% CI) = 0.55 (0.36–0.85) and OS:HR (95% CI) = 0.54 (0.36–0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).Conclusions High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registration Registered with the Clinical Trial Registry of India (Trial registration identifier—CTRI/2014/09/004980).Subject terms: Tumour biomarkers, Head and neck cancer, Tumour biomarkers, Head and neck cancer, Predictive markers     

Myocardial perfusion SPECT reconstruction: Receiver operating characteristic comparison of CAD detection accuracy of filtered backprojection reconstruction with all of the clinical imaging information available to readers and solely stress slices iteratively reconstructed with combined compensation

BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available.     

A skin abscess model for teaching incision and drainage procedures

Background  

Skin and soft tissue infections are increasingly prevalent clinical problems, and it is important for health care practitioners to be well trained in how to treat skin abscesses. A realistic model of abscess incision and drainage will allow trainees to learn and practice this basic physician procedure.     

Simultaneous assessment of cardiac perfusion and function using 5-dimensional imaging with Tc-99m teboroxime

BACKGROUND: Dynamic single photon emission computed tomography (SPECT) acquisition and reconstruction of early poststress technetium 99m teboroxime washout images has been shown to be useful in the detection of coronary disease. Assessment of poststress regional wall motion may offer additional use in assessing coronary disease. Our goal was to investigate the feasibility of simultaneously imaging myocardial ischemia and transient poststress akinesis using gated-dynamic SPECT. METHODS AND RESULTS: A gated-dynamic mathematical cardiac torso (MCAT) phantom was developed to model both teboroxime kinetics and cardiac regional wall motion. A lesion was simulated as having delayed poststress teboroxime washout together with a transient poststress wall motion abnormality. Gated projection data were created to represent a 3-headed SPECT system undergoing a total rotation of 480 degrees . The dynamic expectation-maximization reconstruction algorithm with postsmoothing across gating intervals by Wiener filtering, and the ordered-subset expectation maximization reconstruction algorithm with 3-point smoothing across gating intervals were compared. Compared with the ordered-subset expectation maximization with 3-point smoothing, the dynamic expectation-maximization algorithm with Wiener filtering was able to produce visually higher-quality images and more accurate left ventricular ejection fraction estimates. CONCLUSION: From simulations, we conclude that changing cardiac function and tracer localization possibly can be assessed by using a gated-dynamic acquisition protocol combined with a 5-dimensional reconstruction strategy.     

Rapidly enhancing hepatic hemangiomas at MRI: Distinction from malignancies with T2-weighted images

The purpose of this study is to describe a subset of atypical hepatic hemangiomas that enhance rapidly and diffusely and to determine whether heavily T2-weighted images could distinguish between atypically enhancing liver hemangiomas and hypervascular malignancies. A retrospective search of MR records identified seven patients with liver hemangiomas that demonstrated diffuse early enhancement and 23 patients with biopsy-proven malignant liver lesions that were hypervascular on dynamic gadolinium-enhanced MR images. Quantitative analysis of signal intensity measurements was performed on the T2-weighted images, heavily T2-weighted (TE < 140), and dynamic gadolinium-enhanced images. Blinded reader comparison of the T2-weighted images and gadolinium-enhanced images was performed. Hypervascular hemangiomas enhanced to a greater degree than hypervascular malignant liver lesions on the early phase gadolinium-enhanced images. Perilesional parenchymal enhancement was demonstrated in five cases of rapidly enhancing hemangiomas. Signal intensity and contrast-to-noise ratios on the heavily T2-weighted images of the hemangiomas were significantly greater than that of the hypervascular malignant lesions (P < .05). Hemangiomas were differentiated from the hypervascular malignant liver lesions with high accuracy (97–100%) by three blinded readers based on the T2-weighted images. A subset of hemangiomas have atypical rapid diffuse enhancement on dynamic gadolinium-enhanced images. These atypical hemangiomas can be distinguished from hypervascular malignant liver lesions on T2-weighted MR images.     

Factors affecting patency of internal thoracic artery graft: clinical and angiographic study in 1434 symptomatic patients operated between 1982 and 2002.

OBJECTIVE: The purpose is to define factors influencing long-term patency of the internal thoracic artery (ITA) to optimize the operative strategy. METHODS: 1482 left internal thoracic artery (LITA) and 636 right internal thoracic artery (RITA) symptom-directed angiograms were studied in 1434 patients. Data were prospectively collected from patients who had primary coronary artery bypass surgery during the period 1982-2002. The mean age of patients was 59 years; 85% were male. The mean period from operation to re-angiogram was 80 months. LITA was grafted to left anterior descending coronary artery (LAD) in 82% of cases, RITA to right coronary artery (RCA) in 40% and circumflex artery in 35% of cases. Graft failure was defined as > or =80% stenosis. RESULTS: 96.3% of LITA and 88.1% of RITA grafts were patent. No patient variables were significantly associated with graft patency (age, gender, diabetes, hypertension, LVEF, NYHA, AMI). Target coronary artery was associated with patency of both LITA and RITA grafts with maximum patency when grafted to LAD (P = 0.02) RITA had the worst patency to RCA, patency for the left system was identical to LITA. Proximal anastomosis to aorta (free RITA) had significantly better patency when compared with in situ RITA to RCA system (P = 0.005) while similar patency when grafted to left system. ITA diameter and target artery diameter were not associated with graft patency. Recent operations had better RITA patency (P = 0.03). The interval from operation to angiogram was not associated with ITA patency (96% patency for LITA and 88% patency for RITA, remained stable when studied at <1, 1-4, 5-9, 10-14 and >15 years). CONCLUSIONS: Even in a patient cohort that had adverse symptoms, excellent LITA and RITA patency was achieved which almost remained constant through all time intervals studied.     

Preoperative methicillin‐resistant Staphylococcus aureus (MRSA) screening: An effective method to control MRSA infections on elective orthopaedics wards

Background: Methicillin‐resistant Staphylococcus aureus (MRSA) infections continue to increase in UK hospitals despite the introduction of various control measures. These infections have serious clinical and economic implications, particularly in relation to elective orthopaedic surgery. Methods: A prospective study was performed from August 2003 to July 2004 to assess the effect of preadmission screening and ‘ring fencing’ of beds on the incidence of infection in an elective orthopaedics unit. Results: The preoperative incidence of MRSA colonization was 2.25% and 53% of these patients had at least one risk factor. There were no postoperative MRSA infections in the ring‐fenced orthopaedic unit. Conclusions: Preoperative screening and ring fencing reduced the MRSA incidence to zero in the operated patients. Mechanisms need to be developed where screening and isolation of MRSA cases can be performed in most, if not all, hospital admissions.     

Primary cemented total hip arthroplasty—an Indian experience

We report outcome of 9-year follow-up of 50 Charnley cemented primary arthroplasties in 47 patients performed between 1996 and 1999. The minimum follow-up period was 5 years with a mean of 7 years. All hip joints were thoroughly assessed preoperatively to document patients’ functional level and Harris hip score was calculated. All the patients were disabled because of pain in hip and 45 (90%) had used walking aids. At follow-up all patients were living. The radiographs of all patients were available for the entire follow-up period. Of the 50 operated hips, only 2 patients (4%) complained of pain while all the rest were free of pain. Postoperatively only 10 (20%) patients used support for walking. At follow-up none of the hips were revised. Two patients (4%) had dislocation in postoperative period in which reduction was done under anesthesia. In one patient (2%) prosthesis and cement was removed because of deep infection. In two patients (4%) radiolucent clear zone was seen at bone cement interface on acetabular side and three (6%) patients had it on femoral component. None of the patients developed deep vein thrombosis or heterotopic bone. In postoperative period the Harris hip score was calculated in each case and compared with the preoperative score to evaluate the outcome. Significant improvement was found in Harris hip score after surgery.