Head and neck radiotherapy quality assurance conference for dedicated review of delineated targets and organs at risk: results of a prospective study.

Purpose: Head and neck (HN) radiotherapy (RT) is complex, involving multiple target and organ at risk (OAR) structures delineated by the radiation oncologist. Site-agnostic peer review after RT plan completion is often inadequate for thorough review of these structures. In-depth review of RT contours is critical to maintain high-quality RT and optimal patient outcomes. Materials and Methods: In August 2020, the HN RT Quality Assurance Conference, a weekly teleconference that included at least one radiation oncology HN specialist, was activated at our institution. Targets and OARs were reviewed in detail prior to RT plan creation. A parallel implementation study recorded patient factors and outcomes of these reviews. A major change was any modification to the high-dose planning target volume (PTV) or the prescription dose/fractionation; a minor change was modification to the intermediate-dose PTV, low-dose PTV, or any OAR. We analysed the results of consecutive RT contour review in the first 20 months since its initiation. Results: A total of 208 patients treated by 8 providers were reviewed: 86·5% from the primary tertiary care hospital and 13·5% from regional practices. A major change was recommended in 14·4% and implemented in 25 of 30 cases (83·3%). A minor change was recommended in 17·3% and implemented in 32 of 36 cases (88·9%). A survey of participants found that all (n = 11) strongly agreed or agreed that the conference was useful. Conclusion: Dedicated review of RT targets/OARs with a HN subspecialist is associated with substantial rates of suggested and implemented modifications to the contours.

Patient assessment of lower urinary tract symptoms using the international prostate symptom score following low-dose-rate prostate brachytherapy.

PURPOSE: To correlate changes in urinary patient-reported outcomes including the International Prostate Symptom Score (IPSS), acute urinary retention and urethral stricture with urethral dose in those treated with low dose rate (LDR) prostate brachytherapy. MATERIALS AND METHODS: Patients treated with prostate LDR between 2012 and 2019 (n=117) completed IPSS urinary symptom assessments prior to treatment and at each follow-up. CT simulation was obtained with urinary catheter 1-month post-implant for dosimetric analysis. 113 patients with pre- and ≥1 post-LDR IPSS score available were analyzed. Urethral dosimetric parameters including U75, U100, U125, U150 and U200 were abstracted from post-implant dosimetry and assessed for association with urinary toxicity using bivariate logistic regression and Spearman correlation. Outcomes included clinically significant change (CSC, defined as 4 or more points or 25% rise above baseline) in IPSS score at 6 and 12 months, acute urinary retention (AUR), and urethral stricture (US). RESULTS: 89 (79%) patients were treated with LDR monotherapy (145 Gy) and 24 (21%) with LDR boost (110 Gy) with external beam radiation therapy. Twenty (18%) had baseline IPSS ≥15. Median IPSS scores were: baseline 6 (3-12; n=113), 1-month 17 (10-25; n=110), 6 months 12 (7-18; n=77), 1 year 8 (5-14; n=52). CSC-6 was observed in 59 (77%), CSC-12 in 26 (50%), AUR in 12 (11%), and US in 4 (4%). No association was identified between urethral dose parameters and CSC-6, CSC-12, AUR, or US. No correlation between urethral dose and IPSS at 6- and 12-months was identified. The IPSS ≥15 group exhibited lower rates of CSC-12 (13% v. 57%, p=0.05) but not CSC-6 (55% v. 80%, p=0.12). CONCLUSIONS: We did not find a relationship between urethral dose and IPSS elevation, AUR or US. We did identify a significantly lower change in IPSS at 12 months for those with baseline IPSS ≥15 compared to those with low baseline scores.

The Pharyngolaryngeal Venous Plexus: A Potential Pitfall in Surveillance Imaging of the Neck.

BACKGROUND AND PURPOSE: Among patients undergoing serial neck CTs, we have observed variability in the appearance of the pharyngolaryngeal venous plexus, which comprises the postcricoid and posterior pharyngeal venous plexuses. We hypothesize changes in plexus appearance from therapeutic neck irradiation. The purposes of this study are to describe the CT appearance of the pharyngolaryngeal venous plexus among 2 groups undergoing serial neck CTs-patients with radiation therapy-treated laryngeal cancer and patients with medically treated lymphoma-and to assess for changes in plexus appearance attributable to radiation therapy. MATERIALS AND METHODS: For this retrospective study of 98 patients (49 in each group), 448 contrast-enhanced neck CTs (222 laryngeal cancer; 226 lymphoma) were assessed. When visible, the plexus anteroposterior diameter was measured, and morphology was categorized. RESULTS: At least 1 plexus component was identified in 36/49 patients with laryngeal cancer and 37/49 patients with lymphoma. There were no statistically significant differences in plexus visibility between the 2 groups. Median anteroposterior diameter was 2.1 mm for the postcricoid venous plexus and 1.6 mm for the posterior pharyngeal venous plexus. The most common morphology was "bilobed" for the postcricoid venous plexus and "linear" for the posterior pharyngeal venous plexus. The pharyngolaryngeal venous plexus and its components were commonly identifiable only on follow-up imaging. CONCLUSIONS: Head and neck radiologists should be familiar with the typical location and variable appearance of the pharyngolaryngeal plexus components so as not to mistake them for neoplasm. Observed variability in plexus appearance is not attributable to radiation therapy.

An evaluation of short-term exposures to metalworking fluids in small machine shops.

In a study of 23 small machining shops using metalworking fluids (MWFs), real-time air monitoring using an aerosol photometer was performed to investigate the temporal nature of the exposure and to examine the relationship between the instrumental measurements and traditional sampling methods. Time-weighted averages were calculated from the aerosol photometer data and the results were compared to collocated thoracic and 37-mm closed face cassette samplers. The filter samples were analyzed for total mass and the solvent extractable fraction. Depending on the averaging period used, short-term MWF concentrations exceeded 2.0 mg/m3 in 13 to 39% of the plants studied. High short-term exposures were as likely to be found in plants with average concentrations below 0.4 mg/m3 (thoracic-gravimetric) as those above. Regression analyses indicated that the aerosol photometer most closely matched the data obtained from the thoracic fraction of the total mass. In general, the aerosol photometer overestimated the levels determined using the thoracic cyclone and filter, especially when measuring concentrations of water-based fluids. Use of a calibration factor of 0.7 for straight oils or 0.5 for water-based fluids may assist in the interpretation of aerosol photometer measurements if field calibration data are not readily available. Several approaches to determining the calibration factor from field data were evaluated; more complex calibration techniques improved the accuracy of the measurements.

Metalworking fluid exposures in small machine shops: an overview.

Sampling was conducted in 79 small machine shops to assess airborne exposures to metalworking fluids (MWFs). Measured exposures were compared with data from the literature and exposure criteria currently recommended by the National Institute for Occupational Safety and Health and the Occupational Safety and Health Administration MWF Standards Advisory Committee. Sixty-two percent of 942 personal samples collected were less than the recommended exposure limit (REL) of 0.50 mg/m3 for total particulate. However, at least 1 sample exceeded the REL in 61 of the 79 facilities studied; 100% of the samples collected in 10 shops were greater than the REL. Similar trends were found for thoracic particulate exposures where 75% of 238 samples were below the thoracic particulate REL of 0.40 mg/m3. The ratio between thoracic and total particulate for 238 paired samples was 0.55 (r2=0.73). Workers exposed to straight fluids had the highest exposures (GM=0.67 mg/m3) when compared with workers exposed to other classes of MWFs. The highest exposures were measured for grinding and hobbing (GM=0.67 and 0.60 mg/m3, respectively). Measurements using personal impactors indicated that particle size distributions of MWF aerosols had an average mass median aerodynamic diameter of 5.3 microm. Straight oils and soluble fluids tended to be associated with larger particles than were other fluid types; grinding and turning produced the largest particles, whereas hobbing resulted in the smallest. In general, exposures were similar in magnitude and particle size to those previously reported in large automotive plants. Therefore, workers in these small shops may have risks of adverse health effects similar to those demonstrated in the automotive industry.

The gene encoding protein kinase SEK1 maps to mouse chromosome 11 and human chromosome 17.

We report the mapping of the human and mouse genes encoding SEK1 (SAPK/ERK kinase-1), a newly identified protein kinase that is a potent physiological activator of the stress-activated protein kinases. The human SERK1 gene was assigned to human chromosome 17 using genomic DNAs from human-rodent somatic cell hybrid lines. A specific human PCR product was observed solely in the somatic cell line containing human chromosome 17. The mouse Serk1 gene was mapped to chromosome 11, closely linked to D11Mit4, using genomic DNAs from a (C57BL/6J x Mus spretus)F1 x M. spretus backcross.

Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun.

The stress-activated protein kinases (SAPKs), which are distantly related to the MAP kinases, are the dominant c-Jun amino-terminal protein kinases activated in response to a variety of cellular stresses, including treatment with tumour-necrosis factor-alpha and interleukin-beta (refs 1, 2). SAPK phosphorylation of c-Jun probably activates the c-Jun transactivation function. SAPKs are part of a signal transduction cascade related to, but distinct from, the MAPK pathway. We have now identified a novel protein kinase, called SAPK/ERK kinase-1 (SEK1), which is structurally related to the MAP kinase kinases (MEKs). SEK1 is a potent activator of the SAPKs in vitro and in vivo. An inactive SEK1 mutant blocks SAPK activation by extracellular stimuli without interfering with the MAPK pathway. Although alternative mechanisms of SAPK activation may exist, as an immediate upstream activator of the SAPKs, SEK1 further defines a signalling cascade that couples cellular stress agonists to the c-Jun transcription factor.

Non-transferrin bound iron and neutropenia after cytotoxic chemotherapy.

AIMS: To investigate and characterise the appearance of non-transferrin bound iron (NTBI) in the serum of patients after cytotoxic chemotherapy and to compare this with the onset and duration of neutropenia. METHOD: Non-transferrin bound iron was measured by a bleomycin assay in patients undergoing intensive chemotherapy for treatment of acute leukaemia or lymphoma. RESULTS: NTBI was detected after 26 of 27 courses of chemotherapy and lasted for a mean of 14.5 days. The presence of NTBI correlated with the serum iron binding saturation, but not with serum ferritin. Neutropenia occurred after all courses of chemotherapy and lasted for a mean of 20.0 days. NTBI and neutropenia occurred concurrently after 23 courses of chemotherapy, and had a mean joint duration of 9.5 days. CONCLUSIONS: NTBI is consistently present in the serum of patients after cytotoxic chemotherapy, often at the same time as the patient is neutropenic. This may be an additional risk factor for the development of infective episodes after chemotherapy.

Regulation of iron absorption in iron loaded subjects with end stage renal disease: effects of treatment with recombinant human erythropoietin and reduction of iron stores.

The effects on iron absorption of variation in erythroid activity, haemoglobin and iron stores were studied in six anaemic dialysis-dependent subjects in whom iron stores were increased from previous red cell transfusions. Gastrointestinal mucosal uptake and whole body retention of oral iron were measured at the beginning of the study, after starting treatment with recombinant erythropoietin (but before significant increase in haemoglobin), after partial correction of anaemia, after further reduction of iron stores by repeated phlebotomy, and when erythropoiesis decreased from the discontinuation of treatment with erythropoietin. Between successive measurements, valid comparisons were made in five subjects. Correction of anaemia decreased whole body retention of iron through decreased mucosal uptake (P = 0.032). Further reduction in iron stores through repeated phlebotomy whilst the increase in haemoglobin was maintained by treatment with erythropoietin, tended to increase whole body retention of iron through an increase in mucosal transfer (P = 0.010). With initial enhancement of erythropoiesis in anaemic iron-loaded subjects there was no change in any measured component of iron absorption. However, after correction of anaemia and reduction of iron stores, a decrease in erythropoiesis was associated with decreased whole body iron retention in all subjects through decreased mucosal transfer (P = 0.028). The data suggest that anaemia upregulates mucosal iron uptake, and that erythroid activity upregulates mucosal transfer but that this latter effect may be counter-balanced by iron overload which downregulates mucosal transfer.

Stepwise correction of anaemia by subcutaneous administration of human recombinant erythropoietin in patients with chronic renal failure maintained by continuous ambulatory peritoneal dialysis.

Sixteen anaemic CAPD patients (Hb less than 9 g/dl) were treated with thrice-weekly subcutaneous recombinant erythropoietin, epoetin-alfa. The dose was adjusted to induce a stepwise increase in haemoglobin. Fourteen patients reached a first target haemoglobin of 11.0-11.5 g/dl and eight of these a second of 13.0-13.5 g/dl, but one could not be maintained at this level. Failure to reach or maintain the second target in nine subjects was accounted for by incomplete responses associated with infection in one, extreme shortening of red-cell survival in another, and was unexplained in one subject. These three received the maximum dose studied of 450 IU/kg per week. Six other subjects were withdrawn from the study for reasons unrelated to treatment with erythropoietin. The median dose required to maintain the haemoglobin at 11.0-11.5 g/dl was 75 IU/kg per week and at 13.0-13.5 g/dl was 150 IU/kg per week. Quality of life, assessed in 12 patients at haemoglobin 11.0-11.5 g/dl, showed significant improvement in energy, and at 13.0-13.5 g/dl improvements in sleep and emotional wellbeing became significant. Twelve subjects required either institution of, or an increase in, treatment for hypertension. The thrice-weekly subcutaneous doses of erythropoietin were well tolerated and were a convenient and effective treatment for anaemia in patients on CAPD.

Subcutaneous administration of recombinant human erythropoietin to subjects on continuous ambulatory peritoneal dialysis: an erythrokinetic assessment.

Erythrokinetic studies were performed in subjects on continuous ambulatory peritoneal dialysis, during a trial examining the effectiveness of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) in correcting the anaemia associated with end stage renal disease. 15 subjects (mean haemoglobin concentration 6.9 g/dl, SD 1.1) entered the study, and during treatment 9 were restudied at a haemoglobin concentration of 11-11.5 g/dl and six underwent a third study at haemoglobin 13-13.5 g/dl. By adjusting the dose of r-HuEPO, a stepwise increase in haemoglobin concentration was achieved, and this was accompanied by increases in total red cell volume and erythron transferrin uptake. Plasma volume decreased as red cell volume increased, leaving total blood volume essentially unchanged. Red cell survival, modestly reduced before treatment (mean 64, range 44-96 d, n = 6) tended to increase during treatment and when subjects were retested at a haemoglobin concentration of 13-13.5 g/dl (after 38-62 weeks treatment), the mean increase in red cell survival was 20 d (95% confidence interval 1-39 d). Thus subcutaneous r-HuEPO is effective in correcting the anaemia of end stage renal disease when administered thrice weekly to subjects on continuous ambulatory peritoneal dialysis. It produces an increase in haemoglobin concentration primarily by expanding the erythron, and may have a secondary effect, seen after several months of treatment, of increasing red cell survival.

Evaluation of building ventilation systems.

Over the past several years, NIOSH has responded to health hazard evaluation requests from workers in dozens of office environments. Typically, the employees have complained of headache, eye and upper respiratory tract irritation, dizziness, lethargy and the inability to concentrate. Most often "inadequate ventilation" has been blamed for these complaints. Of paramount importance in the evaluation and correction of these problems is an effective evaluation of the building's ventilation system. Heating, ventilating and air-conditioning conditions that can cause worker stresses include: migration of odors or chemical hazards between building areas; reentrainment of exhaust from building fume hoods or through heat wheels; buildup of microorganisms in the HVAC system components; and poor odor or environmental control due to insufficient "fresh" outdoor air or system heating or cooling malfunction. The purpose of this paper is to provide an overview of building ventilation systems, the ventilation problems associated with poorly designed or operating systems, and the methodology for effectively evaluating system performance.

Improved local exhaust control by directed push-pull ventilation system.

Experiments using the directed push-pull ventilation technique were conducted on a general type of local exhaust ventilation installation. The exhaust (pull) system consisted of a square hood, while the push system consisted of one or two slot jets or two round jets. The two slot or round jets were located behind and beside a mannequin (the mannequin simulated the worker's position). The one slot jet was located between the smoke source and the mannequin. Under experimental conditions, the push-pull system reduced the amount of smoke in the mannequin's breathing zone even when the exhaust system volume flow rate necessary for capture of the smoke decreased approximately 50%. Generally, no difference between the slot and round jet control performance was found. The experiments showed that the directed push-pull ventilation system can be used effectively to reduce the contaminant emission into a workroom, if the jets are located so that the eddy currents induced by the worker or other obstructions are minimized or eliminated.

Development of push-pull ventilation.

Push-pull ventilation (air is blown across a contaminant generation area toward an exhaust hood) can have distinct advantages over exhaust ventilation alone. It can control contaminant emission into the workplace better than exhaust only, and much less conditioned air must be exhausted so there are energy savings. This paper presents suggested push and pull flow rates for open surface tank operations such as plating. About 98% of the contaminant generated can be captured by a push-pull system using the proper flow rates.