Dextran-related complications in head and neck microsurgery: do the benefits outweigh the risks? A prospective randomized analysis

Increased experience with free-tissue transfer has minimized flap loss secondary to microvascular thrombosis, yet pharmacologic antithrombotic prophylaxis continues to be used routinely. Currently there is no consensus on the ideal pharmacologic agent, dosing, or efficacy. Low-molecular-weight dextran has been widely used for prophylaxis due to its properties of volume expansion and enhanced microrheology. Significant systemic morbidity (pulmonary morbidity, cardiac morbidity, anaphylaxis) is known to occur with use of low-molecular-weight dextran. The purpose of this study was to evaluate morbidity associated with postoperative low-molecular-weight dextran and aspirin prophylaxis in head and neck microsurgery patients. This study was a randomized prospective analysis of 100 consecutive patients undergoing microvascular reconstruction for head and neck malignancy during a 2-year period. Patients were randomized into one of three postoperative antithrombotic prophylaxis treatment groups: low-molecular-weight dextran 20 cc/hour for 48 hours (n = 35), low-molecular-weight dextran 20 cc/hour for 120 hours (n = 32), or aspirin 325 mg/day for 120 hours (n = 27). Six patients were excluded intraoperatively due to the need for systemic heparin therapy. Treatment groups were compared for age, sex, prior medical problems, duration of anesthesia, and intraoperative fluid intake. Flap outcome and the incidence of local and systemic complications were evaluated in the treatment groups. Patient ages ranged from 12 to 84 years (mean age, 58 years). No significant difference was found among the treatment groups with respect to age, sex, prior medical problems, duration of anesthesia, intraoperative fluid intake, and the distribution of donor and recipient sites. There were no total flap losses and two partial flap losses in this series. Three flaps were reexplored and all were salvaged. The incidence of systemic complications (congestive heart failure, myocardial infarction, pulmonary edema, pleural effusion, and pneumonia) was as follows: low-molecular-weight dextran 120 hours, 51 percent; low-molecular-weight dextran 48 hours, 29 percent; and aspirin, 7 percent. Analysis of these data suggests that the method of prophylaxis had no effect on overall flap survival. However, the incidence of systemic complications was significantly related to the method of prophylaxis, with patients receiving low-molecular-weight dextran 120 hours and 48 hours at a 7.2 and 3.9 times greater relative risk, respectively, of developing a systemic complication compared with patients receiving aspirin. The results of this study have eliminated the routine use of low-molecular-weight dextran prophylaxis at our institution in an effort to reduce morbidity in head and neck microsurgical reconstruction.     

Escalated hyperfractionation in radiotherapy for head and neck cancer – 5-year results

PurposeTo evaluate 5-year results of escalated hyperfractionation schedule in aspect of local tumour control (LTC) and late radiation toxicity.Material and methodsForty eight patients with squamous cell carcinoma of oral cavity (34 pts), oropharynx (11 pts) and larynx (3) in stage T1-4N0-1 have been treated at Centre of Oncology in Gliwice, between the years 1988–92. There were four patients with T1 primary tumour, 27 with T2, 11 with T3 and 2 with T4; in 4 patients the tumour stage remains unknown (TX). All the patients were treated by radiation therapy alone, using the technique of two opposed parallel fields and hyperfractionation with escalation of the dose per fraction during the second part of the treatment schedule. The total dose ranged between 62,2 and 74 Gy. The median follow-up was 62 months.ResultsDespite of the relative high proportion of complete local regressions (75%), the 5-year LTC rate of 54% was noted in the whole group of patients. Stage-related LTC rates were as follows: 100% for TX tumours, 50% for T1, 55% for T2, 45% for T3 and 0% for T4. Acute radiation reactions were more intensive than those usually observed during conventional radiotherapy; all patients experienced a confluent mucositis and two waves of acute mucosal reaction because of treatment gap were observed during the radiation course. Severe late radiation toxicity (grade IV) was noted in two patients (4%).ConclusionsLong-term tumour control results of escalated hyperfractionation radiotherapy may suggest that there is no benefit of a such regimen. However, in the majority of patients the treatment course differed markedly from protocol assumptions.     

Risk modulation of GSTM1–GSTT1 interactions to head and neck cancer in tobacco users

Tobacco use and environmental air pollution are the established etiological factors in head and neck cancer (HNC) progression. Nevertheless, not all the inhabitants with high usage of tobacco from the same polluted locality are suffering with HNC and this is due to the existence of factors like inter-individual genetic polymorphisms, life time exposure to tobacco and the rate of xenobiotic metabolism enzyme (XME) activity. The present study investigates the polymorphic genotypes of the most important XME, glutathione-S-transferase Mu 1 (GST M1) and Theta 1 (GST T1) as the risk modulator to HNC among tobacco-habituated inhabitants of Saurashtra in Gujarat, a region in western India. A population based case–control study was done in 252 HNC patients and 504 healthy controls. Blood samples were collected from the subjects and investigated for polymorphic genotypes of GST M1 and GST T1. Estimation of the odds of risks was done by logistic regressions. Among the subjects with high usage of tobacco, M1 not null-T1 null genotypes presence was found as risk reducing factor to HNC with 0.334 folds (95 % CI; 0.170–0.659). The presence of M1 null-T1 not null genotypes was found with susceptibility to HNC among the subjects with no habit of tobacco chewing, adjusted odds ratio (AOR) 3.170 (1.128–8.913) and no habit of smoking, AOR of 2.544 (1.094–5.963). The present study reveals the finding of significantly increased risk to HNC by interactions of GST M1 null-GST T1 not null polymorphic genotypes among the subjects with nil or less tobacco usage shed some light for the insights of biomarker application in early detection of HNC.     

The short and long term effects of exercise training in non-cystic fibrosis bronchiectasis – a randomised controlled trial

Background

Exercise training is recommended for non-cystic fibrosis (CF) bronchiectasis, but the long-term effects are unclear. This randomised controlled trial aimed to determine the effects of exercise training and review of airway clearance therapy (ACT) on exercise capacity, health related quality of life (HRQOL) and the incidence of acute exacerbations in people with non-CF bronchiectasis.

Methods

Participants were randomly allocated to 8 weeks of supervised exercise training and review of ACT, or control. Primary outcomes of exercise capacity and HRQOL (Chronic respiratory disease questionnaire) and secondary outcomes of cough-related QOL (Leicester cough questionnaire) and psychological symptoms (Hospital anxiety and depression scale) were measured at baseline, following completion of the intervention period and at 6 and 12 months follow up. Secondary outcomes of the exacerbation rate and time to first exacerbation were analysed over 12 months.

Results

Eighty-five participants (mean FEV₁ 74% predicted; median Modified Medical Research Council Dyspnoea grade of 1 (IQR [1–3]) were included. Exercise training increased the incremental shuttle walk distance (mean difference to control 62 m, 95% CI 24 to 101 m) and the 6-minute walking distance (mean difference to control 41 m, 95% CI 19 to 63 m), but these improvements were not sustained at 6 or 12 months. Exercise training reduced dyspnoea (p = 0.009) and fatigue (p = 0.01) but did not impact on cough-related QOL or mood. Exercise training reduced the frequency of acute exacerbations (median 1[IQR 1–3]) compared to the control group (2[1–3]) over 12 months follow up (p = 0.012), with a longer time to first exacerbation with exercise training of 8 months (95% CI 7 to 9 months) compared to the control group (6 months [95% CI 5 to 7 months], p = 0.047).

Conclusions

Exercise training in bronchiectasis is associated with short term improvement in exercise capacity, dyspnoea and fatigue and fewer exacerbations over 12 months.

Trial registry

ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT00885521","term_id":"NCT00885521"}}NCT00885521).     

Systematic analysis of differentially methylated expressed genes and site-specific methylation as potential prognostic markers in head and neck cancer

Head and neck cancer (HNC) remains one of the most malignant tumors with a significantly high mortality. DNA methylation exerts a vital role in the prognosis of HNC. In this study, we try to screen abnormal differential methylation genes (DMGs) and pathways in Head–Neck Squamous Cell Carcinoma via integral bioinformatics analysis. Data of gene expression microarrays and gene methylation microarrays were obtained from the Cancer Genome Atlas database. Aberrant DMGs were identified by the R Limma package. We conducted the Cox regression analysis to select the prognostic aberrant DMGs and site-specific methylation. Five aberrant DMGs were recognized that significantly correlated with overall survival. The prognostic model was constructed based on five DMGs (PAX9, STK33, GPR150, INSM1, and EPHX3). The five DMG models acted as prognostic biomarkers for HNC. The area under the curve based on the five DMGs predicting 5-year survival is 0.665. Moreover, the correlation between the DMGs/site-specific methylation and gene expression was also explored. The findings demonstrated that the five DMGs can be used as independent prognostic biomarkers for predicting the prognosis of patients with HNC. Our study might lay the groundwork for further mechanism exploration in HNC and may help identify diagnostic biomarkers for early stage HNC.     

Short term response is predictive of long term response to acetylcholinesterase inhibitors in Alzheimer’s disease: A starting point to explore Bayesian approximation in clinical practice

This study was aimed at identifying, in 203 patients with Alzheimer''s disease followed during long-term treatment with Acetylcholinesterase inhibitors (ChEIs), the predictive factors of the clinical response among cognition (MMSE), functioning (BADL and IADL) measures and age and gender at the baseline (T0). The ANCOVA test showed a significant association between MMSE scores at time T0 and T3, and the variation T9 to T0, T15 to T0 and T21 to T0 of the MMSE scores, using also gender, age and drug as covariates. The significance was higher for the patients affected by mild dementia. Regarding functional activities, a significant relationship was detected, by the ANCOVA test, only between the scores at T3 and the variation T15 to T0 for BADL, and the variation T9 to T0, T15 to T0 for IADL, respectively. Our results confirm, in a real world setting, that ChEIs provide long-term cognitive benefit, which is correlated to, and predictable by, the short-term response (within the third month) as well as the cognitive status (evaluated by means of the MMSE) at the beginning of the treatment. These factors should be the basis of any cost/effectiveness algorithm in health economic decision models.     

Species Richness and Assemblages in Landscapes of Different Farming Intensity – Time to Revise Conservation Strategies?

Worldwide conservation goals to protect biodiversity emphasize the need to rethink which objectives are most suitable for different landscapes. Comparing two different Swedish farming landscapes, we used survey data on birds and vascular plants to test whether landscapes with large, intensively managed farms had lower richness and diversity of the two taxa than landscapes with less intensively managed small farms, and if they differed in species composition. Landscapes with large intensively managed farms did not have lower richness than smaller low intensively managed farms. The landscape types were also similar in that they had few red listed species, normally targeted in conservation. Differences in species composition demonstrate that by having both types of agricultural landscapes regional diversity is increased, which is seldom captured in the objectives for agro-environmental policies. Thus we argue that focus on species richness or red listed species would miss the actual diversity found in the two landscape types. Biodiversity conservation, especially in production landscapes, would therefore benefit from a hierarchy of local to regional objectives with explicit targets in terms of which aspects of biodiversity to focus on.     

Behaviour,survival and glycogen utilisation in the baltic isopod Saduria entomon exposed to long‐term oxygen depletion

The benthic isopod Saduria entomon was exposed to different oxygen saturations (92, 6, and < 1%, T = 8°C). The behaviour of S. entomon under hypoxia and anoxia differs from that observed under normoxia. During the first few hours under low oxygen conditions animals became more active. After that time they lay motionless on the sediment surface. A few of them were partially buried. When oxygenation decreased, the percentage of individuals that emerged from the sediment rapidly increased. It was four and seven times higher under hypoxia and anoxia, respectively. S. entomon is able to survive long periods (41 days) under severe hypoxia, whereas the LT₅₀ under anoxia varied between 12 and 18 days according to animal size. The glycogen content, which is the essential substrate for anaerobic metabolism of this species, decreased after 41 days under anoxia down to 48% of the normoxic level.     

Trunk and hip muscle activity in early walkers with and without cerebral palsy – A frequency analysis

Poor control of postural muscles is a primary impairment in cerebral palsy (CP), yet core trunk and hip muscle activity has not been thoroughly investigated. Frequency analysis of electromyographic (EMG) signals provides insight about the intensity and pattern of muscle activation, correlates with functional measures in CP, and is sensitive to change after intervention. The objective of this study was to investigate differences in trunk and hip muscle activation frequency in children with CP compared to children with similar amounts of walking experience and typical development (TD). EMG data from 31 children (15 with CP, 16 with TD) were recorded from 16 trunk and hip muscles bilaterally. A time–frequency pattern was generated using the continuous wavelet transform and instantaneous mean frequency (IMNF) was calculated at each interval of the gait cycle. Functional principal component analysis (PCA) revealed that IMNF was significantly higher in the CP group throughout the gait cycle for all muscles. Additionally, stride-to-stride variability was higher in the CP group. This evidence demonstrated altered patterns of trunk and hip muscle activation in CP, including increased rates of motor unit firing, increased number of recruited motor units, and/or decreased synchrony of motor units. These altered muscle activation patterns likely contribute to muscle fatigue and decreased biomechanical efficiency in children with CP.     

SOD1 in amyotrophic lateral sclerosis development – in silico analysis and molecular dynamics of A4F and A4V variants

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized by the selective loss of motor neurons. Approximately 5% to 10% of patients with ALS have a family history of the disease, and approximately 20% of familial amyotrophic lateral sclerosis (fALS) cases are associated with mutations in Cu/Zn superoxide dismutase (SOD1). In this study, we evaluated the structural and functional effects of human A4F and A4V SOD1 protein mutations. We performed an in silico analysis using prediction algorithms of nonsynonymous single-nucleotide polymorphisms (nsSNPs) associated with the fALS development. Our structural conservation results show that the mutations analyzed (A4V and A4F) were in a highly conserved region. Molecular dynamics simulations using the Linux GROMACS package revealed how these mutations affect protein structure, protein stability, and aggregation. These results suggest that there might be an effect on the SOD1 function. Understanding the molecular basis of disease provides new insights useful for rational drug design and advancing our understanding of the ALS development.     

Comparison of positron emission tomography/computed tomography imaging and ultrasound in surveillance of head and neck cancer – The 3-year experience of the ENT Department in Poznan

Background

Posttreatment surveillance for the local and regional recurrence of the head and neck squamous cell carcinoma often requires a multimodality techniques that include PET combined with CT, MRI, US.

Aim

The purpose of this study is to compare the diagnostic performance of two imaging techniques (PET/CT and US), and their combined use for the detection of a subclinical regional recurrence in patients after HNSCC treatment.

Materials and methods

83 patients after completion of the HNSCC treatment underwent both US and PET/CT on the mean follow-up of 14 months after initial treatment.

Results

The sensitivity and specificity of PET/CT were 86% and 82%, respectively; US values reached 81% and 87%, respectively. PPV was 79% for PET/CT, and 83% for US. NPV was 89% for PET/CT, and 85% for US. The overall accuracy for PET/CT and US was 84% for both methods.

Conclusion

US could be regarded as complementary to PET/CT as the procedures with highest sensitivity, specificity and NPV for detecting subclinical regional recurrences after HNSCC treatment.     

Phase I study of α-galactosylceramide-pulsed antigen presenting cells administration to the nasal submucosa in unresectable or recurrent head and neck cancer

Background Human Vα24 natural killer T (NKT) cells are activated by the specific ligand, α-galactosylceramide (α-GalCer), in a CD1d-dependent manner. Potent anti-tumor activity of activated NKT cells has been previously demonstrated. Methods We conducted a phase I study with α-GalCer-pulsed antigen presenting cells (APCs) administered in the nasal submucosa of patients with head and neck cancer, and evaluated the safety and feasibility of such a treatment. Nine patients with unresectable or recurrent head and neck cancer received two treatments 1 week apart, of 1 × 10⁸ of α-GalCer-pulsed autologous APCs into the nasal submucosa. Results During the clinical study period, no serious adverse events (Common Terminology Criteria for Adverse Events version 3.0 greater than grade 3) were observed. After the first and the second administration of α-GalCer-pulsed APCs, an increased number of NKT cells was observed in four patients and enhanced natural killer activity was detected in the peripheral blood of eight patients. Conclusion The administration of α-GalCer-pulsed APCs into the nasal submucosa was found to be safe and induce anti-tumor activity in some patients.     

Changes in soil phosphorus fractions in response to long‐term phosphate fertilization under sole cropping and intercropping of maize and faba bean on a calcareous soil

Plant and Soil - Understanding how soil phosphorus (P) fractions change is critical to achieve more efficient soil P use in a highly P-sorbing calcareous soil. The fields were managed without or...     

A comparative analysis of heat waves and associated mortality in St. Louis, Missouri – 1980 and 1995

 This research investigates heat-related mortality during the 1980 and 1995 heat waves in St. Louis, Missouri. St. Louis has a long history of extreme summer weather, and heat-related mortality is a public health concern. Heat waves are defined as days with apparent temperatures exceeding 40.6°C (105°F). The study uses a multivariate analysis to investigate the relationship between mortality and heat wave intensity, duration, and timing within the summer season. The heat wave of 1980 was more severe and had higher associated mortality than that of 1995. To learn if changing population characteristics, in addition to weather conditions, contributed to this difference, changes in population vulnerability between 1980 and 1995 are evaluated under simulated heat wave conditions. The findings show that St. Louis remains at risk of heat wave mortality. In addition, there is evidence that vulnerability has increased despite increased air-conditioning penetration and public health interventions. Received: 12 August 1997 / Revised: 12 January 1998 / Accepted: 13 February 1998     

Neo-adjuvant chemotherapy ± immunotherapy with s.c. IL 2 in advanced squamous cell carcinoma of the head and neck: A pilot study

We carried out a pilot nonrandomized phase II study to compare the neo-adjuvant chemotherapic regimen with cisplatin, 5-FU and vinorelbine with the same combination plus s.c. IL 2 in advanced head and neck squamous cell carcinoma (HNSCC). The primary goals of the trial were to evaluate the feasibility and response rates of the two regimens. The study design consisted of a patient's assignment to either of the two following arms: Arm A: Cisplatin 80 mg/m² i.v. on day 1; 5-FU 600 mg/m² i.v. on days 2–5; and vinorelbine 20 mg/m² i.v. on days 2 and 8, Arm B: the same chemotherapic regimen plus recombinant IL 2 (Proleukin, Eurocetus) 9 MIU s.c. daily from day 9 to 13 and from day 16 to 20 for every cycle. From March 1993 to November 1993 twenty three patients with Stage III–IV HNSCC were enrolled in the study. Patients could be evaluated for response to treatment if they had received at least 2 complete cycles of therapy. The overall response rate (ORR) was 63% in Arm A and 100% in Arm B. The differences for ORR and CR rates were statistically significant in favor of Arm B. The analysis for each of the three drugs included in the chemotherapy schedule shows that both the actually received average dose-intensity and the actually delivered average cumulative doses/patient were higher for Arm B (chemo- plus IL 2 therapy) (approximately 80% of programmed dose-intensity) than for Arm A (approximately 70% of programmed dose-intensity). Both the actually received average dose-intensity and the actually delivered average cumulative doses/patient for IL 2 were more than 80%. In both arms the most frequent side effects were myelosuppression, phlebitis and electrolyte disturbances. There were 2 toxic deaths, 1 in Arm A and 1 in Arm B, both for hematologic toxicity. Our pilot study suggests that the combination of cisplatin, 5-FU, vinorelbine plus IL 2 is a highly active, but rather toxic, neo-adjuvant treatment in advanced HNSCC with very high ORR and CR rates.     

Two Doses of Candidate TB Vaccine MVA85A in Antiretroviral Therapy (ART) Na?ve Subjects Gives Comparable Immunogenicity to One Dose in ART+ Subjects

Tuberculosis (TB) is a global public health problem exacerbated by the HIV epidemic. Here we evaluate a candidate TB vaccine, MVA85A, in a Phase I study in HIV-infected adults in Senegal. 24 patients were enrolled: Group 1∶12, antiretroviral therapy (ART) naïve, adults, with CD4 counts >300 and HIV RNA load <100 000 copies/ml. Group 2∶12 adults, stable on ART, with CD4 counts >300, and an undetectable HIV RNA load. Safety was evaluated by occurrence of local and systemic adverse events (AEs) and by monitoring of CD4 count, HIV RNA load, haematology and biochemistry. Immunogenicity was evaluated by ex-vivo interferon-gamma ELISpot assay. 87.7% of AEs were mild; 11.6% were moderate; and 0.7% were severe. 29.2% of AEs were systemic; 70.8% were expected local AEs. There were no vaccine-related Serious Adverse Events (SAEs) or clinically significant effects on HIV RNA load or CD4 count. In ART naive subjects, the first MVA85A immunisation induced a significant immune response at 1 and 4 weeks post-immunisation, which contracted to baseline by 12 weeks. Durability of immunogenicity in subjects on ART persisted out to 24 weeks post-vaccination. A second dose of MVA85A at 12 months enhanced immunogenicity in ART naïve subjects. Subjects on ART had higher responses after the first vaccination compared with ART naïve subjects; responses were comparable after 2 immunisations. In conclusion, MVA85A is well-tolerated and immunogenic in HIV-infected subjects in Senegal. A two dose regimen in ART naïve subjects is comparable in immunogenicity to a single dose in subjects on ART.Clinicaltrials.gov trial identifier {"type":"clinical-trial","attrs":{"text":"NCT00731471","term_id":"NCT00731471"}}NCT00731471.