The Effects of Human Papillomavirus Status and Treatment on the Positive Predictive Value of Post-radiotherapy 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Advanced Head and Neck Squamous Cell Carcinoma.

AIMS: The high negative predictive value of post-chemoradiation (CRT) positron emission tomography-computed tomography (PET-CT) is well established in head and neck squamous cell cancers (HNSCC). The positive predictive value (PPV) remains under scrutiny, with increasing evidence that it is affected by several factors. The aim of this study was to assess the PPV of post-treatment PET-CT for residual nodal disease when stratified by treatment modality and tumour human papillomavirus (HPV) status. MATERIALS AND METHODS: This was a retrospective cohort study in a tertiary oncology centre carried out between January 2013 and December 2019. Patients were radically treated with radiotherapy only/CRT for node-positive HNSCC. PET-CT nodal responses were categorised as complete, equivocal (EQR) or incomplete (ICR), and outcomes extracted from electronic records. RESULTS: In total, 480 patients were evaluated, all had a minimum potential follow-up of 2 years, with a median of 39.2 months. The PPV of 12-week PET-CT was significantly different between HPV-positive (22.5%) and HPV-unrelated (52.7%) disease, P < 0.001. It was also significantly different between the CRT (24.8%) and radiotherapy-only (51.1%) groups, P = 0.001. The PPV of an EQR was significantly less than an ICR, irrespective of HPV status and primary treatment modality. In HPV-positive disease, the PPV of an EQR was 9.0% for the CRT group compared with 21.4% for radiotherapy only, P = 0.278. The PPV in those who achieved an ICR was 34.2% in the CRT group, significantly lower than 70.0% in the radiotherapy-only group, P = 0.03. CONCLUSION: The PPV of 12-week PET-CT is significantly lower for HPV-positive compared with HPV-unrelated HNSCC. It is poorer in patients with HPV-positive disease treated with CRT compared with radiotherapy alone.

Positron Emission Tomography-Computed Tomography Surveillance after (Chemo)Radiotherapy in Advanced Head and Neck Squamous Cell Cancer: Beyond the PET-NECK Protocol.

AIMS: To evaluate the implementation of 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) surveillance after (chemo)radiotherapy, to compare outcomes for those who achieved a complete (CR), equivocal (EQR) and incomplete (ICR) nodal response on 12-week PET-CT according to their human papillomavirus (HPV) status, and to assess the safety of ongoing surveillance beyond 12 weeks in the HPV-positive EQR group. MATERIALS AND METHODS: All patients with node-positive head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy between January 2013 and September 2017 were identified. PET-CT responses were classified as CR, ICR or EQR. Patient outcomes were obtained from electronic records. RESULTS: In total, 236 patients with a minimum of 2 years of follow-up were identified. The mean age was 59 years; 79.3% had N2 disease; 77.1% of patients had oropharyngeal cancer and 10.1% had squamous cell carcinoma of unknown primary, of whom 82.0% (169) were HPV positive; 78.0% received chemoradiotherapy. The median time from the end of radiotherapy to PET-CT was 91 days. Of the HPV-related HNSCC, 60.4% achieved CR, 29.0% EQR and 10.6% ICR. With a median follow-up of 41.7 months, there was no difference in survival between patients with HPV-related HNSCC achieving CR and EQR (median overall survival not reached for both, P = 0.67) despite the omission of immediate neck dissection in 98.0% of the EQR group. CONCLUSION: Patients with HPV-positive HNSCC who have achieved EQR have comparable survival outcomes to those who achieved a CR despite the omission of immediate neck dissections; this shows the safety of ongoing surveillance beyond 12 weeks in this group of patients.

Influence of the level of sacrectomy on survival in patients with locally advanced and recurrent rectal cancer.

BACKGROUND: Exenterative surgery for locally advanced rectal cancer may involve partial sacrectomy to achieve complete resection. High sacrectomy is technically challenging, and can be associated with high morbidity and mortality rates. The aim of this study was to determine the influence of the level of sacrectomy on the survival of patients with locally advanced rectal cancer. METHODS: This was an international multicentre retrospective analysis of patients undergoing exenterative abdominosacrectomy between July 2006 and June 2016. High sacrectomy was defined as resection at or above the junction of S2-S3; low sacrectomy was below the S2-S3 junction. Kaplan-Meier survival analysis was used to assess overall survival and cancer-specific survival. Predictive factors were determined using Cox regression analysis. RESULTS: A total of 345 patients were identified, of whom 91 underwent high sacrectomy and 254 low sacrectomy. There was no difference in 5-year overall survival (53 versus 44·1 per cent; P = 0·216) or cancer-specific survival (60 versus 56·1 per cent; P = 0·526) between high and low sacrectomy. Negative margin rates were similar for primary and recurrent disease: 65 of 90 (72 per cent) versus 97 of 153 (63·4 per cent) (P = 0·143). Level of sacrectomy was not a significant predictor of mortality (P = 0·053). Positive resection margin and advancing age were the only significant predictors for death, with hazard ratios of 2·78 (P < 0·001) and 1·02 (P = 0·020) respectively. CONCLUSION: There was no survival difference between patients who underwent high or low sacrectomy. In appropriately selected patients, high sacrectomy is feasible and safe.

The relationship of systemic markers of haemostasis with retinal blood vessel responses in cardiovascular disease and/or diabetes.

Background Hypercoagulability is a leading factor in diabetes and cardiovascular disease. Retinal vessel responses to flickering light are an important tool for assessing ocular function. We hypothesised a significant relationship between systemic markers of haemostasis and retinal vessel function. Methods Intra-ocular pressure and retinal microcirculation function were measured in 116 patients with diabetes and/or cardiovascular disease using unstimulated and stimulated arterial and venous retinal vessel responses to flickering light. Haemostasis was evaluated by platelet microparticles, soluble P selectin, and five functional markers of fibrin clot formation and lysis, hyperglycaemia by HbA1c. Results Intra-ocular pressure was linked to the rates of clot formation (p = 0.006) and clot dissolution (p = 0.013) whilst central retinal vein equivalent was linked to HbA1c (p = 0.017). In the first of three flickering light cycles only, arterial baseline diameter fluctuation was linked to the lag time to clot formation (p = 0.017), whilst maximum venous dilatation was linked to HbA1c (p = 0.001) and clot density (p = 0.011). HbA1c was linked to venous dilatation amplitude (p = 0.003). There were no significant links between any ocular index and any platelet index. Conclusions In addition to glycaemia, several haemostasis measures, but no measures of platelet activity, are linked to ocular and retinal blood vessel indices in patients with diabetes and/or cardiovascular disease. These associations may have pathophysiological significance.

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses.

PURPOSE: To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease. METHODS: Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index. RESULTS: Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p < 0.05). Arterial reaction time was linked to serum creatinine (p = 0.036) and eGFR (p = 0.039); venous reaction time was linked to creatinine clearance (p = 0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p < 0.001 and p = 0.003, respectively) and the dilatation amplitude (p = 0.038 and p = 0.048, respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p = 0.004) and dilatation amplitude (p = 0.017), vWf was linked to the maximum constriction response (p = 0.016), and creatinine clearance to the baseline diameter fluctuation (p = 0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p = 0.022). CONCLUSIONS: Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses.

Laboratory assessment of anti-thrombotic therapy in heart failure, atrial fibrillation and coronary artery disease: insights using thrombelastography and a micro-titre plate assay of thrombogenesis and fibrinolysis.

As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p < 0.05). In multivariate regression analysis, only microplate assay indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p < 0.001) in aspirin users. Three microplate assay indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk.

Electrical stimulation at the dorsal root ganglion preserves trabecular bone mass and microarchitecture of the tibia in hindlimb-unloaded rats.

SUMMARY: This study seeks to investigate the effect of electrical stimulation (ES) at dorsal root ganglion (DRG) on disuse bone loss in a rat model. Hindlimb unloading for 14 days resulted in significant bone loss in rat tibia while rats with ES at DRG showed a significant reduced bone loss INTRODUCTION: Mechanical unloading induces osteoporosis in both human and animals. Previous studies demonstrated that electrical stimulation (ES) to dorsal root ganglion (DRG) could trigger secretion of calcitonin gene-related peptide (CGRP) which plays an important role in bone modeling and remodeling. This study seeks to investigate the effect of ES to DRG on disuse bone loss in a rat model. METHODS: Twenty-four rats were randomly assigned in three experimental groups: cage control (CC), hindlimb unloading (HU), and hindlimb unloading with ES (HUES). ES was applied via implantable micro-electrical stimulators (IMES) to right DRGs at vertebral levels L4-L6 in HUES group. RESULTS: Hindlimb unloading for 14 days resulted in 25.9% decrease in total bone mineral content (BMC), 29.2% decrease in trabecular BMD and trabecular microarchitecture and connectivity were significantly deteriorated in the proximal tibia metaphysis in HU group, while rats with ES at DRG showed significant reduced bone loss that there was 3.8% increase in total BMC, 2.3% decrease in trabecular BMD, and significant improvement in trabecular microarchitecture. There was a concurrent enhancement of expression of CGRP in stimulated DRGs. CONCLUSIONS: The results confirm the effect of ES at DRG on enhancing CGRP expression and suggest potential applications of IMES for the prevention and treatment of disuse bone loss.

Cubic Mn2Ga thin films: crossing the spin gap with ruthenium.

Cubic Mn2Ga films with the half-Heusler C1b structure are grown on V (001) epitaxial films. The phase is a soft ferrimagnet, with Curie temperature TC = 225 K and magnetization Ms=280 kA m(-1), equivalent to 1.65µB per formula. Adding ruthenium leads to an increase of TC up to 550 K in cubic Mn2Ru(x)Ga films with x = 0.33 and a collapse of the net magnetization. The anomalous Hall effect changes sign at x = 0.5, where the sign of the magnetization changes and the magnetic easy direction flips from in plane to perpendicular to the film. The Mn2Ru0.5Ga compound with a valence electron count of 21 is identified as a zero-moment ferrimagnet with high spin polarization, which shows evidence of half-metallicity.

Controlled release of an antibiotic, gentamicin sulphate, from gravity spun polycaprolactone fibers.

The antibiotic, gentamicin sulphate (GS), was incorporated in gravity-spun polycaprolactone (PCL) fibers by spinning from particulate suspensions of the drug in PCL solution to produce a controlled delivery system. The production rate of GS-loaded PCL fibers was confined to the range 1-1.5 m/min and the fiber diameter to 170-220 microm. The kinetics of drug release could be adjusted by varying the GS loading of the fibers and the suspension preparation conditions. Gradual release of approximately 80% of the initial GS content was measured in phosphate buffered saline at 37 degrees C over 50 days from fibers spun from nonhomogenized suspensions, whereas loss of this amount of antibiotic occurred in less than 10 days from fibers spun from homogenized suspensions. Studies of growth inhibition of Stapyhlococcus epidermidis in culture indicated that GS released after 2 weeks from PCL fibers retained antibacterial activity. This behavior recommends further investigation of PCL fibers for local delivery of antibiotics to combat infection associated with periodontal disease, musculoskeletal injuries, and implantation of fiber-based tissue substitutes such as vascular prostheses.

One-stage posterior decompression and fusion using a Luque rod for occipito-cervical instability and neural compression.

STUDY DESIGN: Original article. OBJECTIVE: The authors present seven cases who underwent one-stage suboccipital, C1 and/or C2 posterior decompression and fusion by Luque rod, wiring and autogenic bone graft for occipito-cervical instability and neural compression. SETTING: Chang Gung University and Medical Center at Kaohsiung, Taiwan. METHOD: Since January 1996, 20 cases of craniovertebral and upper cervical spinal instability were encountered. Seven of these cases had no neurological improvment under Cone-Barton Skeletal traction. Imaging studies revealed poor reduction with persistent neural compression. One patient underwent unsuccessful anterior trans-oral vertebrectomy for decompression. All patients underwent posterior suboccipital craniectomy, C1 and/or C2 laminectomy for decompression. Contoured Luque rod with wiring and autogeneic bone graft was used for craniocervical fusion. After surgical treatment, halo-vest or sterno-occipito-mandibular immobilizer (SOMI) was used for 3-6 months. RESULTS: Suboccipital craniectomy and C1 laminectomy could afford a 30-50% increment of anteroposterior diameter in the neural canal and effective decompression of the low medulla and cord. All patients made neurological improvement. The ASIA-MIS scores improved from pre-operative 49 (mean) to 78. Four patients can walk without any support. There were no major complications except for one case requiring readjustment of the halo-vest brace. CONCLUSION: The authors recommend this procedure as one choice for relieving craniocervical instability with neurological compromise. A programmed rehabilitation will afford better neurological improvement.

Study of low-temperature thermoplastic modified custom-molded cervical orthosis for cervical spine fixation.

The purpose of this experiment is to use a low-temperature thermoplastic material (Aquaplast) to make a modified custom-molded cervical orthosis. Sixteen normal young subjects who do not have previous cervical problems are tested in this study. This modified orthosis is applied on these volunteers so that external fixation of the cervical spine can be tested. Various roentgenograms for cervical flexion and extension, as well as neutral position and lateral bending, are taken to determine the fixation property of the cervical spine. A study of rotation of the cervical spine is also carried out through goniometer measurements. This clinical study proves that this low-temperature thermoplastic cervical orthosis provides good fixation for the cervical spine, especially in flexion and rotation, but is not suitable for C1- and C2-injured patients.

Time--concentration studies by high-performance liquid chromatography of metabolites removed during hemodialysis.

Reversed-phase high-performance liquid chromatography was used to study the efficiency of hemodialysis. The method, previously used to study uremic hemodialysate, was also found useful for analyzing other uremic biofluids, such as serum and urine. Samples of blood (centrifuged to obtain cell-free serum) and hemodialysate were simultaneously collected from selected patients at regular intervals during the entire 6-hour hemodialysis treatment. These samples were filtered through membranes to remove particulates and proteins and were then analyzed by use of a 60-cm muBondapak-C18 column, an aqueous sodium acetate/methanol gradient, and detection at 254 nm. The identification of components in the eluate was based on retention times, ultraviolet absorption spectra, and mass spectra. From the amounts of several metabolites in the various physiological fluid pools during hemodialysis, we concluded that they mostly originate from tissue fluids. We also observed that the concentrations of most components in serum and hemodialysate fluctuated regularly with time.