Intensity-modulated proton therapy (IMPT) versus intensity-modulated radiation therapy (IMRT) for the treatment of head and neck cancer: A dosimetric comparison.

It is the goal of this study to compare the dosimetric advantages of IMPT when compared to IMRT. From January 2019 to August 2020, 25 patients were treated with intensity modulated proton therapy (IMPT) at our institution for either recurrent, metastatic, benign, or primary tumors in the head and neck region. Twenty-one patients met criteria for dosimetric analysis. Histology of disease included squamous cell carcinoma, acinic cell carcinoma, sarcomatoid sinonasal carcinoma, paraganglioma, adenoid cystic carcinoma, salivary high grade carcinoma, and papillary thyroid carcinoma. For IMRT planning, gross tumor volume (GTV) and clinical target volume (CTV) were contoured with the expansion of 3-5 mm to create the planning target volume (PTV) and dose was prescribed to the PTV. For the IMPT planning, dose was prescribed to CTV and robust optimization was utilized which accounted for a 5 mm setup and range uncertainty. The minimum, mean and maximum target doses for IMRT and IMPT plans as well as mean and maximum normal tissue doses are reported for the 21 patients meeting criteria. Mean doses for IMRT and IMPT were 6278.2 cGy and 6449.8 cGyRBE respectively with p-value of 0.0001. Maximum doses for IMRT and IMPT were 6579.5 cGy and 6772.1 cGyRBE respectively with p-value of 0.0014. Minimum doses for IMRT and IMPT were 5440.6 cGy and 5617.9 cGyRBE respectively with p-value of 0.3576. IMPT had an overall advantage in OAR doses in the brain stem, spinal cord, optic structures, cochlea, larynx, contralateral parotid, and oral cavity with only a few exceptions. Our study thus demonstrates a dosimetric advantage for IMPT in treating head and neck tumors in mean and max dose delivered as well as dose to OARs. Given that our patient cohort were mainly unilateral head and neck cases, our study supports the treatment of this specific subset of patients regardless of histology with IMPT. This may aid in appropriate patient selection for IMPT treatment. Further studies will need to determine if this dosimetric advantage translates to a therapeutic advantage for patients.

Progress Toward Long-Term Survivors of Glioblastoma.

OBJECTIVE: To identify the frequency and characteristics of long-term survivors of glioblastoma. PATIENTS AND METHODS: Using all cases of glioblastoma with histopathological confirmation in the National Cancer Database from January 1, 2004, through December 31, 2009, clinical, institutional, and treatment-related factors were evaluated with multivariable logistic regression models so as to elucidate factors independently associated with higher than 5-year overall survival after diagnosis. RESULTS: A total of 48,652 patients met the inclusion criteria, with 2249 (4.6%) achieving 5-year survival. Factors associated with odds of improved 5-year overall survival in multivariable analysis were younger age, female sex, less medical comorbidities, nonwhite race, highest median income quartile, left-sided tumors and tumors outside the brainstem, and treatment with radiotherapy (P<.05 for all). The percentage of patients surviving 5 years remained relatively unchanged over the 6-year study period (P=.97). CONCLUSION: Despite improvements in median and short-term overall survival shown in recent large clinical trials for glioblastoma, the percentage of patients with glioblastoma achieving 5-year overall survival remains low. This observation calls for the development of practice-redefining therapies and justifies the increased application of radical novel and experimental treatment paradigms for all patients with glioblastoma.

Effects of enamel fluorosis and dental caries on quality of life.

The objectives of this study were to determine the impact of enamel fluorosis and dental caries on oral health-related quality of life (OHRQoL) in North Carolina schoolchildren and their families. Students (n = 7,686) enrolled in 398 classrooms in grades K-12 were recruited for a onetime survey. Parents of students in grades K-3 and 4-12 completed the Early Childhood Oral Health Impact Scale (ECOHIS) and Family Impact Scale (FIS), respectively. Students in grades 4-12 completed the Child Perceptions Questionnaire (CPQ8-10 in grades 4-5; CPQ11-14 in grades 6-12). All students were examined for fluorosis (Dean's index) and caries experience (d2-3fs or D2-3MFS indices). OHRQoL scores (sum response codes) were analyzed for their association with fluorosis categories and sum of d2-3fs and D2-3MFS according to ordinary least squares regression with SAS procedures for multiple imputation and analysis of complex survey data. Differences in OHRQoL scores were evaluated against statistical and minimal important difference (MID) thresholds. Of 5,484 examined students, 71.8% had no fluorosis; 24.4%, questionable to very mild fluorosis; and 3.7%, mild, moderate, or severe fluorosis. Caries categories were as follows: none (43.1%), low (28.6%), and moderate to high (28.2%). No associations between fluorosis and any OHRQoL scales met statistical or MID thresholds. The difference (5.8 points) in unadjusted mean ECOHIS scores for the no-caries and moderate-to-high caries groups exceeded the MID estimate (2.7 points) for that scale. The difference in mean FIS scores (1.5 points) for the no-caries and moderate-to-high groups exceeded the MID value (1.2 points). The sum of d2-3fs and D2-3MFS scores was positively associated with CPQ11-14 (B = 0.240, p < .001), ECOHIS (B = 0.252, p ≤ .001), and FIS (B = 0.096, p ≤ .01) scores in ordinary least squares regression models. A child's caries experience negatively affects OHRQoL, while fluorosis has little impact.

The role of interventional radiology in complications after paediatric liver transplantation.

Liver transplantation has become an established treatment in both adults and children for end-stage liver disease, acute hepatic failure and certain liver tumours. There is a significant risk of complications after all forms of liver transplantation. The interventional radiologist plays a critical role in the diagnosis and treatment of these complications. The use of image-guided, minimally invasive procedures reduces the need for surgical revision or retransplantation and improves graft and patient survival rate. This article reviews some of the most common vascular and non-vascular complications after paediatric liver transplantation, and the interventional radiology techniques used to diagnose and treat them.

Pegylated liposomal doxorubicin plus carboplatin in patients with metastatic breast cancer: a phase II study.

BACKGROUND: We determined the objective response rates produced by pegylated liposomal doxorubicin (PLD) plus carboplatin with/without trastuzumab (Herceptin). PATIENTS AND METHODS: Patients with measurable disease were stratified by taxane treatment history and human epidermal growth factor receptor-2 status. TREATMENT: PLD 30 mg/m(2) followed by carboplatin, day 1 of each 28-day cycle; human epidermal growth factor receptor-2 (HER2)-positive patients also received trastuzumab. RESULTS: Arm 1 received PLD plus carboplatin (N = 41 arm 1a, taxane naive; N = 42 arm 1b, taxane pretreated); Arm 2 patients received PLD plus carboplatin + Herceptin (N = 46). Overall response rates: 31%, 31%, and 56%, respectively. Median overall survival durations were not reached in arm 1a and were 13 and 33 months for arms 1b and 2. Median progression-free survival: 8, 5, 10 months, respectively. Grades 3-4 treatment-related toxic effects for arms 1a, 1b, 2, respectively, were neutropenia 22%, 31%, 35%; thrombocytopenia 34%, 26%, 17%; and fatigue 2%, 14%, 13%. CONCLUSIONS: PLD plus carboplatin has moderate antitumor activity and excellent tolerability. Herceptin and PLD plus carboplatin in HER2-positive patients have antitumor activity without significant cardiac toxicity. Toxicity results suggest that PLD can be combined with Herceptin with minimal cardiac toxicity.

Safety and immunogenicity of a Shigella flexneri 2a Invaplex 50 intranasal vaccine in adult volunteers.

Shigellosis is a leading cause of diarrhea worldwide prompting vaccine development. The Shigella flexneri Invaplex 50 is a macromolecular complex containing IpaB, IpaC, and LPS, formulated from an aqueous extract of virulent Shigella delivered via nasal administration. Preclinical vaccine testing demonstrated safety, immunogenicity and efficacy. An open-label dose-escalating phase 1 study evaluated a 3-dose (2-week intervals) regimen via nasal pipette delivery. Thirty-two subjects were enrolled into one of four vaccine dose groups (10, 50, 240, or 480 microg). The vaccine was well tolerated with minor short-lived nasal symptoms without evidence of dose effect. Antibody-secreting cell (ASC) responses were elicited at doses > or =50 microg with the highest IgG ASC, Invaplex 50 (100%) and S. flexneri 2a LPS (71%), as well as, serologic responses (43%) occurring with the 240 microg dose. Fecal IgA responses, Invaplex 50 (38.5%) and LPS (30.8%), were observed at doses > or =240 microg. The Invaplex 50 nasal vaccine was safe with encouraging mucosal immune responses. Follow-on studies will optimize dose, delivery mechanism and assess efficacy in a S. flexneri 2a challenge study.

A collaborative approach to the implementation of clinical supervision.

AIM: This paper discusses a collaborative approach to implementing clinical supervision, which was initiated between a primary care trust and a school of nursing and midwifery. BACKGROUND: To enable clinical supervision to proceed successfully and to be perceived as beneficial, this necessitates a collaborative partnership between clinicians, managers and educationalists. KEY ISSUES: The different stages of the initiative will be explored and the paper will consider examples of the collaborative processes involved. The evaluation of the project is examined and suggestions for the future continuation of the initiative are discussed. CONCLUSION: There is evidence that this has been a successful initiative and that a collaborative way of working can be beneficial when implementing clinical supervision.

Mitoxantrone and paclitaxel combination chemotherapy in metastatic breast cancer.

This study evaluated mitoxantrone and paclitaxel combination chemotherapy in the treatment of patients with metastatic breast cancer. Thirty-seven patients who had developed progressive disease after prior chemotherapy were treated with mitoxantrone (14 mg/m2) and paclitaxel (150 mg/m2) every 21 days for a maximum of six cycles. The most frequent grade 3 or 4 nonhematological toxicities were fever and nausea. Grade 4 neutropenia occurred in 71% of patients. Cardiotoxicity occurred in 2 patients, both of whom had previously received doxorubicin. Objective response was achieved in 35% of patients (5% complete response and 30% partial response) and 41% had stable disease. Median time to disease progression and median survival were 6 and 12 months, respectively. The percent of patients with an objective response was not different for those who had received prior doxorubicin or had chemotherapy in the preceding 6 months. This regimen appears to be effective and well tolerated as salvage therapy and merits further evaluation.

Factors associated with long-term progression or stability in primary open-angle glaucoma.

PURPOSE: To evaluate long-term risk factors for progression or stability in patients with primary open-angle glaucoma. METHOD: We retrospectively included consecutively reviewed patients who had primary open-angle glaucoma for at least 5 years in this multicenter trial. Historical and clinical factors in these patients were evaluated for their association with stability or progression of the glaucoma. RESULTS: We included 218 patients in this study; of these, 34 progressed over an average length of follow-up of 45.5 +/- 30.0 months, and 184 were stable over an average of 72.8 +/- 18.3 months. The mean intraocular pressure over the follow-up period for the progressed group was 19.5 +/- 3.8 mm Hg and for the stable group 17. 2 +/- 3.1 mm Hg (P =.001). The average standard deviation of individual intraocular pressures was greater in the progressed group (5.1 mm Hg) than the stable group (3.9 mm Hg, P =.012). Baseline characteristics indicating a greater potential to progress were a larger cup-to-disk ratio (P <.001), a greater number of medications (P =.02), older age (P.007), and worse visual acuity (P =.003). However, no difference was observed in pressure levels that prevented progression in these subpopulations compared with the total sample size. CONCLUSIONS: This study suggests that lowering the intraocular pressure is important in the treatment of primary open-angle glaucoma to help prevent long-term progression. Lowering the pressure, however, is not uniformly effective in preventing progression. Additionally, risk factors for progression do not further help identify pressure levels that prevent worsening of glaucoma.

Transdermal extraction of interstitial fluid by low-frequency ultrasound quantified with 3H2O as a tracer molecule.

The transdermal extraction of interstitial fluid by low-frequency ultrasound offers a potential minimally invasive method of obtaining a fluid sample for at-home blood glucose monitoring. Here we show that the application of low-frequency ultrasound (20 kHz) enhances the transdermal transport of interstitial fluid across hairless rat skin. Using 3H2O as a tracer injected intravenously, a measurable amount of water (>1 microL) was extracted without producing any histologic evidence of injury, even after repeated exposures. Piezoelectric transducers were imbedded in the extraction chamber and used to correlate ultrasound spectral properties to the amount of fluid extracted. Results indicate that the highest amount of water extracted occurs when the acoustic coupling media on the surface of the skin is cavitating, resulting in mild ablation of the stratum corneum and a reduction in its resistance to water mass transfer.

3-O-Desacyl monophosphoryl lipid A derivatives: synthesis and immunostimulant activities.

The synthesis of a series of novel analogues of lipid A, the active principle of lipopolysaccharide, is reported. In these compounds, the 1-O-phosphono and (R)-3-hydroxytetradecanoyl moieties of native Salmonella minnesota R595 lipid A have been replaced with hydrogen and the length of the normal fatty acyl residues has been systematically varied. Normal fatty acid chain length in the 3-O-desacyl monophosphoryl lipid A (MLA) series is shown to be a critical determinant of iNOS gene expression in activated mouse macrophages and the induction of proinflammatory cytokines in human peripheral monocytes. Examination of pyrogenicity in rabbits and lethal toxicity in D-galactosamine-treated mice shows that toxic effects in the MLA series can be ameliorated by modifying fatty acid chain length. When used as an adjuvant for tetanus toxoid vaccines, certain MLA derivatives enhance the production of tetanus toxoid-specific antibodies in mice.

Synthesis and biological evaluation of a new class of vaccine adjuvants: aminoalkyl glucosaminide 4-phosphates (AGPs).

A novel series of acylated omega-aminoalkyl 2-amino-2-deoxy-4-phosphono-beta-D-glucopyranosides (aminoalkyl glucosaminide 4-phosphates) was synthesized and screened for immunostimulant activity. Several of these compounds enhance the production of tetanus toxoid-specific antibodies in mice and augment vaccine-induced cytotoxic T cells against EG.7-ova target cells.

The presence and sequence of endotracheal tube colonization in patients undergoing mechanical ventilation.

Endotracheal tube colonization in patients undergoing mechanical ventilation was investigated. In the first part of this prospective study, the airway access tube was examined for the presence of secretions, airway obstruction and bacterial colonization, in cases undergoing extubation or tube change. In the second part of the study, the sequence of oropharyngeal, gastric, respiratory tract and endotracheal tube colonization was investigated by sequential swabbing at each site twice daily for 5 days in consecutive noninfected patients. In the first part, it was noted that all airway access tubes of cases undergoing extubation had secretions lining the interior of the distal third of the tube which were shown on scanning electron microscopy to be a biofilm. Gram-negative micro-organisms were isolated from these secretions in all but three cases. In the second part, it was noted that the sequence of colonization in patients undergoing mechanical ventilation was the oropharynx (36 h), the stomach (3660 h), the lower respiratory tract (60-84 h), and thereafter the endotracheal tube (60-96 h). Nosocomial pneumonia occurred in 13 patients and in eight cases identical organisms were noted in lower respiratory tract secretions and in secretions lining the interior of the endotracheal tube. The endotracheal tube of patients undergoing mechanical ventilation becomes colonized rapidly with micro-organisms commonly associated with nosocomial pneumonia, and which may represent a persistent source of organisms causing such infections.

The rotator cuff-deficient arthritic shoulder: diagnosis and surgical management.

The symptomatic rotator cuff-deficient, arthritic glenohumeral joint poses a complex problem for the orthopaedic surgeon. Surgical management can be facilitated by classifying the disorder in one of three diagnostic categories: (1) rotator cuff-tear arthropathy, (2) rheumatoid arthritic shoulder with cuff deficiency, or (3) degenerative arthritic (osteoarthritic) shoulder with cuff deficiency. If it is not possible to repair the cuff defect, surgical management may include prosthetic arthroplasty, with the recognition that only limited goals are attainable, particularly with respect to strength and active motion. Glenohumeral arthrodesis is a salvage procedure when other surgical measures have failed. Arthrodesis is also indicated in patients with deltoid muscle deficiency. Humeral hemiarthroplasty avoids the complications of glenoid loosening and is an attractive alternative to arthrodesis, resection arthroplasty, and total shoulder arthroplasty. The functionally intact coracoacromial arch should be preserved to reduce the risk of anterosuperior subluxation. Care should be taken not to "overstuff" the gleno-humeral joint with a prosthetic component. In cases of significant internal rotation contracture, subscapularis lengthening is necessary to restore anterior and posterior rotator cuff balance. If the less stringent criteria of Neer's "limited goals" rehabilitation are followed, approximately 80% to 90% of patients treated with humeral hemiarthroplasty can have satisfactory results.

Noninvasive measurement of pulsatile intracranial pressure using ultrasound.

The present study was designed to validate our noninvasive ultrasonic technique (pulse phase locked loop: PPLL) for measuring intracranial pressure (ICP) waveforms. The technique is based upon detecting skull movements which are known to occur in conjunction with altered intracranial pressure. In bench model studies, PPLL output was highly correlated with changes in the distance between a transducer and a reflecting target (R2 = 0.977). In cadaver studies, transcranial distance was measured while pulsations of ICP (amplitudes of zero to 10 mmHg) were generated by rhythmic injections of saline. Frequency analyses (fast Fourier transformation) clearly demonstrate the correspondence between the PPLL output and ICP pulse cycles. Although theoretically there is a slight possibility that changes in the PPLL output are caused by changes in the ultrasonic velocity of brain tissue, the decreased amplitudes of the PPLL output as the external compression of the head was increased indicates that the PPLL output represents substantial skull movement associated with altered ICP. In conclusion, the ultrasound device has sufficient sensitivity to detect transcranial pulsations which occur in association with the cardiac cycle. Our technique makes it possible to analyze ICP waveforms noninvasively and will be helpful for understanding intracranial compliance and cerebrovascular circulation.

A comparison of efficacy of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in the therapeutic setting of chemotherapy-induced myelosuppression.

A randomized, double-blind, multicenter study in 181 afebrile cancer patients with ANC levels < 500/microL receiving myelosuppressive chemotherapy was undertaken to compare sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the treatment of chemotherapy-induced myelosuppression. Patients received daily subcutaneous (SC) injections of either agent until ANC levels reached at least 1500/microL. There was no statistical difference between treatment groups in the mean number of days to reach an ANC of 500/microL, but the mean number of days to reach ANC levels of 1000/microL and 1500/microL was approximately one day less in patients receiving filgrastim. Fewer patients in the sargramostim arm were hospitalized, and they had a shorter mean length of hospitalization, mean duration of fever, and mean duration of i.v. antibiotic therapy compared with patients who received filgrastim. Both growth factors were well tolerated. No patient was readmitted to the hospital after growth factor was discontinued. Sargramostim and filgrastim have comparable efficacy and tolerability in the treatment of standard-dose chemotherapy-induced myelosuppression in community practice.

District nurses' perceptions of health education.

This paper presents a small qualitative study examining district nurses' perceptions of health education in one community trust. District nurses perceive health education to be an important part of the role. There are various factors that both facilitate and constrain the district nurses' health education role. District nurses feel that it is essential that their health education role is valued by other health care professionals; therefore evaluation of this function is seen as significant.

Intracranial pressure dynamics during simulated microgravity using a new noninvasive ultrasonic technique.

It is believed that intracranial pressure (ICP) may be elevated in microgravity because a fluid shift toward the head occurs due to loss of gravitational blood pressures. Elevated ICP may contribute to space adaptation syndrome, because as widely observed in clinical settings, elevated ICP causes headache, nausea, and projectile vomiting, which are similar to symptoms of space adaptation syndrome. However, the hypothesis that ICP is altered in microgravity is difficult to test because of the invasiveness of currently-available techniques. We have developed a new ultrasonic technique, which allows us to record ICP waveforms noninvasively. The present study was designed to understand postural effects on ICP and assess the feasibility of our new device in future flight experiments.

Low-dose carbon monoxide does not reduce vasoconstriction in isolated rat lungs.

Recent studies have demonstrated that nitric oxide (NO) acts as a pulmonary vasodilator when inhaled in low concentrations. Due to the physicochemical similarities between NO and carbon monoxide (CO), it was speculated that low concentrations of CO would have similar effects in the isolated rat lung. The purpose of this study was to determine the role of CO (200 and 1000 ppm) in modulating hypoxia- and angiotensin II (AII)-induced pulmonary vasoconstriction, using isolated salt-perfused lungs of normotensive (CON) or pulmonary hypertensive male rats. Pulmonary hypertensive rats (ALT), induced by simulated altitude exposure (4572 m; 430 mm Hg for 32-48 days), were studied to determine the actions of low-dose CO in a remodeled pulmonary vascular bed. Right ventricular hypertrophy and polycythemia were evident in the ALT rats, suggesting that simulated altitude exposure induced pulmonary hypertension and consequent pulmonary vascular remodeling. CO did not significantly affect pulmonary vascular responses to acute hypoxia (6% CO2, balance N2) in either CON or ALT rats. There were also no significant differences in pulmonary pressor responses to AII injections (0.2 or 0.4 micrograms) in CON or ALT lungs either immediately following or during an acute hypoxia + CO exposure. Therefore, acute low-dose CO exposure (< 1000 ppm) does not appear to attenuate pulmonary vasoconstriction in isolated rat lungs.