A measure of SRS/SRT plan quality: Quantitative limits for intermediate dose spill (R50%) in linac-based delivery.

Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) of multiple cranial targets using a single isocenter on conventional C-arm linear accelerators are rapidly developing clinical techniques. However, no universal guidelines for acceptable intermediate dose spill limits are currently available or widely accepted. In this work, we propose an intermediate dose spill guidance range for cranial SRS/SRT delivered on C-arm linacs with MLC collimation for single PTV plans and single isocenter multiple target plans with PTV volumes in the range 0.02-57.9 cm3 . We quantify intermediate dose spill with the R50% metric (R50% = volume of 50% of prescription isodose cloud / volume of PTV) and test the proposed range using three clinical data sets, containing both 6 MV and 10 MV beams, previously published by other authors. Our proposed lower limit of R50% (LowerR50%) and upper limit of acceptable R50% (UpperR50%) bound over 90% of the clinical data used in this study, yet still provide a challenging benchmark for optimization and plan assessment of linac-based, MLC collimated SRS/SRT.

Efficient optimization of R50% when planning multiple cranial metastases simultaneously in single isocenter SRS/SRT.

Simultaneous optimization of multiple Planning Target Volumes (PTVs) of varying size and location in the cranium is a non-trivial task. The rate of dose falloff around PTV structures is variable and depends on PTV characteristics such as the volume. The metric R50% is one parameter that can be used to quantify dose falloff achieved in a given treatment plan. An important treatment planning question is how to construct optimization conditions that result in the efficient production of acceptable plan outcomes considering metrics such as R50%. Guidance provided in literature suggests generating multiple shell control structures around each PTV. The constraints applied to these shells can vary significantly depending on PTV volume. Additionally, there is no clear guidance on how to prospectively determine objective constraints for the optimization shells to achieve a specified goal of R50%. Based on physical principles and empirical evidence, we provide clear quantitative guidance on how to translate the desired R50% outcome into appropriately sized optimization structures around PTVs via an equation that depends on a desired goal for R50% and the volume of PTV. Optimization schema are also provided that allow the goal R50% to be approached or achieved for all PTVs individually. We demonstrate the application of the methodology using commercially available treatment planning software and radiotherapy treatment equipment.

An analytical expression for R50% dependent on PTV surface area and volume: A cranial SRS comparison.

The intermediate dose spill for a stereotactic radiosurgery (SRS) plan can be quantified with the metric R50%, defined as the 50% isodose cloud volume (VIDC50% ) divided by the volume of the planning target volume (PTV). By coupling sound physical principles with the basic definition of R50%, we derive an analytical expression for R50% for a spherical PTV. Our analytical expression depends on three quantities: the surface area of PTV (SAPTV ), the volume of PTV (VPTV ), and the distance of dose drop-off to 50% (Δr). The value of ∆r was obtained from a simple set of cranial phantom plan calculations. We generate values from our analytical expression for R50% (R50%Analytic ) and compare the values to clinical R50% values (R50%Clinical ) extracted from a previously published SRS data set that spans the VPTV range from 0.15 to 50.1 cm3 . R50%Analytic is smaller than R50%Clinical in all cases by an average of 15% ± 7%, and the general trend of R50%Clinical vs VPTV is reflected in the same trend of R50%Analytic . This comparison suggests that R50%Analytic could represent a theoretical lower limit for the clinical SRS data; further investigation is required to confirm this. R50%Analytic could provide useful guidance for what might be achievable in SRS planning.

The surface area effect: How the intermediate dose spill depends on the PTV surface area in SRS.

PURPOSE: Stereotactic radiosurgery (SRS) is rapidly becoming the standard of care for many intracranial targets. The characteristics of the planning target volume (PTV) can affect the intermediate dose spill and thus normal brain volume dose which is correlated with brain toxicity. R50% (volume receiving 50% of prescription dose divided by PTV volume) is a useful metric to quantify the intermediate dose spill. We propose a novel understanding of how the PTV surface area (SAPTV ) affects the intermediate dose spill of SRS treatments. METHODS: Using a phantom model provided by a computed tomography (CT) of the IROC Head Phantom® and Eclipse® Treatment Planning System, we investigate the relationship of R50% and SAPTV in single-target SRS treatments. The planning studies are conducted for SRS treatments on a Varian TrueBeam® linear accelerator with high-definition MLC and a 6 MVFFF beam mode. These data are analyzed to ascertain trends in R50% related to SAPTV . Since SAPTV is not available as a structure property in the Eclipse RTPS, we introduce an Eclipse script to extract PTV surface area of arbitrary-shaped PTVs. We compare a physically reasonable theoretical prediction of R50%, R50%Analytic , to the R50% achieved in treatment planning studies. RESULTS: The SRS phantom study indicates good correlation between the plan R50% and SAPTV . A near-linear relationship of plan R50% vs SAPTV is observed as predicted by the R50%Analytic model. Agreement between plan R50% values and R50%Analytic predictions is good for all but the very smallest PTV volumes. CONCLUSIONS: We demonstrate dependence of the intermediate dose spill measured by R50% on the SAPTV . We call that dependence the surface area effect. This dependence is explicit in the R50%Analytic prediction model. The predicted value of R50%Analytic for a given PTV could be used for guidance during SRS treatment plan optimization, and plan evaluation for that PTV.

A physically meaningful relationship between R50% and PTV surface area in lung SBRT.

PURPOSE: We propose a novel understanding of two characteristics of the planning target volume (PTV) that affect the intermediate-dose spill in lung stereotactic body radiation therapy (SBRT) as measured by R50%. This phantom model research investigates two characteristics of the PTV that have a marked effect on the value of R50%: the mean dose deposited within the PTV (Dav ) and the surface area of the PTV (SAPTV ). METHODS: Using a phantom model provided by a CT of the IROC Thorax-Lung Phantom® (IROC Houston QA Center, Houston, TX) and Eclipse® Treatment Planning System (Varian Medical Systems, Palo Alto, CA), we investigate the two characteristics for spherical and cylindrical PTVs. A total of 135 plans with tightly controlled PTV characteristics are employed. A lower bound for R50% (R50%min∆r ) is derived and clearly establishes a relationship between R50% and SAPTV that has not been fully appreciated previously. RESULTS: The study of PTV Dav revealed a local minimum for R50% as a function of the PTV Dav at Dav  ≈ 110% of Rx dose. As PTV Dav increases above this local minimum, R50% increases; while for PTV Dav less than this local minimum, the R50% value also increases. The study of PTV surface area (SAPTV ) demonstrated that as the SAPTV increases, the R50% increases if the PTV volume stays the same. The SAPTV result is predicted by the theoretical investigation that yields the R50% lower bound, R50%min∆r . CONCLUSIONS: This research has identified two characteristics of the PTV that have a marked influence on R50%: PTV Dav and SAPTV . These characteristics have not been clearly articulated in the vast body of previous research in SBRT. These results could help explain plans that cannot meet the RTOG criteria for R50%. With further development, these concepts could be extended to provide additional guidance for creating acceptable SBRT plans.

An analytical expression for R50% dependent on PTV surface area and volume: a lung SBRT comparison.

In stereotactic body radiation therapy (SBRT), R50% is a common metric for intermediate dose spill and is defined in RTOG 0915 as the ratio of 50% isodose cloud volume (IDC50%) to the planning target volume (PTV). By coupling sound physical principles with the basic definition of intermediate dose spill, we derive an exact analytical expression for R50% for the case of a spherical volume. This expression for R50% depends on three quantities: the surface area of PTV (SAPTV ), the volume of PTV (VPTV ), and the dose gradient Δr. Validity of our analytical expression for R50% was confirmed via direct comparison to peer-reviewed, multi-institutional, diverse clinical data. The comparison of our R50% values computed from our analytical expression to the clinical data yielded an average percent difference of 3.8 ± 4.5%.

Changes in reproductive physiology of mangrove rivulus Kryptolebias marmoratus following exposure to environmentally relevant doses of ethinyl oestradiol.

Kryptolebias marmoratus exposed to 4 ng l(-1) of ethinyl oestradiol (EE2) for 30 days experienced significant changes in endogenous 17ß-oestradiol (E2) and 11-ketotestosterone (KT) and qualitative changes in gonad morphology. Both hermaphrodites and males showed a significant decrease in E2, whereas only males exhibited a significant decrease in KT. Exposure to EE2 resulted in a decrease in spermatid and spermatocyte density in males and an increase in the number of early stage oocytes in hermaphrodites.

Traumatic Zone II Flexor Tendon Injury Repair Through a Traumatic Dorsal Approach.

Zone II flexor tendons present unique challenges for repair because of their complex anatomy in a confined space. The approach for zone II injuries is often dictated by preexisting traumatic skin lacerations, with a midaxial or volar approach being most common. In some injuries, this approach is not viable, and alternative approaches must be considered. A 45-year-old man presented with a traumatic crush injury that caused complete disruption of the skin, tendon, capsule, collateral ligament, and volar plate and laceration of the flexor digitorum profundus in zone II near the proximal interphalangeal joint. Given the large, near-circumferential zone of injury, we used the traumatic dorsal wound for the flexor tendon for repair. There are no reports of this approach in the literature. Postoperatively, the proximal interphalangeal joint was immobilized for 6 weeks with a K-wire. The patient was followed in the clinic and prescribed occupational therapy. At the 4-month postoperative visit, the patient had a healed incision, no signs of infection, and intact median/radial sensations. Functional testing showed a loose composite fist, improved range of motion, and 2-cm tip-to-palm deficiency of the index finger. Grip strength was 85 lb in the right hand and 60 lb in the left hand. Although patients are not always expected to regain full function, their postoperative course may be further complicated by adhesion and the need for tenolysis. Given these historical complications of tendon repair and our patient's ability to return to work with satisfactory functional outcomes, this approach may be a viable option for treating this unique injury pattern. [Orthopedics. 2022;45(4):e216-e219.].

Stemless Total Shoulder Arthroplasty for a 4-Part Proximal Humerus Malunion and Post-traumatic Arthritis: A Case Report.

CASE: We present a 62-year-old left-hand-dominant woman with history of renal failure, osteoporosis, and 4-part proximal humerus fracture malunion with subsequent post-traumatic arthritis of the left glenohumeral joint. After conservative treatments failed to relieve her symptoms, the patient underwent stemless total shoulder arthroplasty (TSA) because of concerns that her proximal humerus could not accommodate a stemmed implant. At 2 and a half-years postoperative, the patient demonstrated significant improvement of symptoms without signs of radiographic loosening. CONCLUSION: In the setting of proximal humerus malunion with post-traumatic arthritis, clinical improvement without implant loosening can be achieved with stemless TSA, even in the setting of compromised bone quality.

Migration depths of adult steelhead Oncorhynchus mykiss in relation to dissolved gas supersaturation in a regulated river system.

Adult steelhead Oncorhynchus mykiss tagged with archival transmitters primarily migrated through a large river corridor at depths >2 m interspersed with frequent but short (<5 min) periods closer to the surface. The recorded swimming depths and behaviours probably provided adequate hydrostatic compensation for the supersaturated dissolved gas conditions encountered and probably limited development of gas bubble disease (GBD). Results parallel those from a concurrent adult Chinook salmon Oncorhynchus tshawytscha study, except O. mykiss experienced greater seasonal variability and were more likely to have depth uncompensated supersaturation exposure in some dam tailraces, perhaps explaining the higher incidence of GBD in this species.

Triceps Tendon Rupture - A Novel Repair of an Uncommon Injury.

INTRODUCTION: Triceps tendon rupture is a rare injury accounting for <1% of all tendon injuries with varying repair techniques described. We present this novel repair to supplement available literature and help optimize the clinical outcomes for affected patients. We report this technique because it is unique in that we augmented our surgical fixation with a subtle variation in the described technique by repairing the deep portion of the triceps tendon as a separate step, maximizing the recreation of the anatomic footprint of the triceps. CASE REPORT: The patient is a 70-year-old Caucasian male presenting with pain, swelling, and ecchymosis around the elbow after the episode of injury. He also complained of a painful popping sensation whenever he ranged the elbow and an inability to extend, with pain and weakness any time he attempted elbow extension. Radiographs reviewed at his initial visit revealed a small osseous fragment approximately 5 cm proximal to the olecranon tip. Subsequent MR imaging confirmed our suspicion, showing a complete tear of the triceps tendon with hematoma at its insertion site and tendon retraction approximately 3 cm proximally. With the diagnosis of triceps tendon rupture conformed, we took the patient for primary tendon repair using suture with bone bridge and suture anchor, using elements from described techniques. Our technique was unique in that we performed repair of the deep and superficial triceps attachments as separate steps, in an endeavor to improve the anatomic reconstruction of the footprint and biomechanical strength. CONCLUSIONS: We combined findings from our review of the available literature with novel surgical techniques and suture design to maximize the patient outcome and minimize complications. The patient went on to have a very satisfactory functional recovery. We hope that this case report will complement the evidence-based care of these patients by orthopedic surgeons and lead to the best results possible.

Novel Use of Joint Replacement in a Thumb Interphalangeal Joint.

Arthrodesis of the interphalangeal (IP) joint of the thumb is widely acknowledged as the indicated treatment for trauma and osteoarthritis of this joint. Joint replacement was offered to a young patient as an alternative treatment after traumatic joint loss of the IP joint in her thumb. This allowed her to maintain motion of the joint as she did not wish to move forward with fusion. In the present case, a Humanitarian Use Device (HUD) was utilized in an off-label manner and placed into the interphalangeal joint of the patient's thumb. The patient did well postoperatively with reasonable pain-free range of motion of the interphalangeal joint with an arc of 40 degrees. We propose that joint replacement is a viable alternative to arthrodesis in select patients who do not wish to be fused. We believe this represents the first thumb IP joint replacement using a semiconstrained joint presented in the medical literature.

Early post-operative opioid consumption: A comparison between medial unicompartmental, patellofemoral, and total knee arthroplasty.

BACKGROUND: While there is emerging literature describing the use of narcotics for post-operative pain control following TKA, little data is available regarding narcotic use in partial knee replacements. The aim of this study is to compare the early post-operative narcotic requirements after medial compartmental arthroplasty (UKA) and patellofemoral arthroplasty (PFA) with that of TKA. METHODS: In this retrospective chart review, we identified 37 patients who underwent PFA and 71 patients who underwent UKA. We identified a cohort of TKA patients who were matched to the unicompartmental group based on sex and age (n = 108). The primary outcome measure was self-reported use of opioids for pain management at the first post-operative clinic visit. Opioid use between groups was compared using Chi-square analysis. RESULTS: The PFA group was younger (p < 0.001) and consisted of more females (p < 0.001) than the UKA group. The UKA cohort had more non-smoking patients (p = 0.044) compared to the PFA cohort. Self-reported opioid use at the first post-operative visit differed between the three groups of patients (p < 0.001). A greater proportion of both PFA (38% vs. 11%; p < 0.001) and TKA (41% vs. 11%; p = 0.01) patients reported opioid use when compared to UKA patients. No differences in opioid use existed between TKA and PFA groups (p = 0.61). CONCLUSION: The prevalence of PFA patients who report opioid use at the first post-operative visit is similar to that for patients following TKA, suggesting that pain management protocols for this specific subset of partial knee arthroplasty patients should be structured similar to TKA patients and separate from UKA patients.

Direct brain recordings reveal prefrontal cortex dynamics of memory development.

Prevailing theories link prefrontal cortex (PFC) maturation to the development of declarative memory. However, the precise spatiotemporal correlates of memory formation in the developing brain are not known. We provide rare intracranial evidence that the spatiotemporal propagation of frontal activity supports memory formation in children. Seventeen subjects (6.2 to 19.4 years) studied visual scenes in preparation for a recognition memory test while undergoing direct cortical monitoring. Earlier PFC activity predicted greater accuracy, and subsecond deviations in activity flow between subregions predicted memory formation. Activity flow between inferior and precentral sites was refined during adolescence, partially explaining gains in memory. In contrast, middle frontal activity predicted memory independent of age. These findings show with subsecond temporal precision that the developing PFC links scene perception and memory formation and underscore the role of the PFC in supporting memory development.

Agents, mechanisms and clinical features of non-scald burns in children: A prospective UK study.

AIMS: To inform childhood burn prevention by identifying demographics, clinical features and circumstances of unintentional non-scald burns. METHODS: A prospective cross-sectional study was conducted across Cardiff, Bristol and Manchester, including six emergency departments, three minor injury units and one burns unit between 13/01/2013-01/10/2015. Data collected for children aged <16 years with any burn (scald, contact, flame, radiation, chemical, electrical, friction) included: demographics, circumstances of injury and clinical features. Scalds and burns due to maltreatment were excluded from current analysis. RESULTS: Of 564 non-scald cases, 60.8% were boys, 51.1% were <3 years old, 90.1% (472/524) of burns affected one anatomical site. Contact burns accounted for 86.7% (489/564), 34.8% (137/394) of which were from objects placed at >0.6m and 76.5% (349/456) affected the hands. Hairstyling devices were the most common agent of contact burns (20.5%, 100/487); 34.1% (30/88) of hairstyling devices were on the floor. Of children aged 10-15 years, 63.7% (65/102), sustained contact burns of which 23.2% (13/56) were preparing food, and when burnt from hairstyling devices, 73.3% (11/15) were using them at the time of injury. CONCLUSIONS: Parents of toddlers must learn safe storage of hazardous items. Older children should be taught skills in safe cooking and hairstyling device use.

Structure-activity relationships for reactivity of carbonyl-containing compounds with glutathione.

For toxicological-based structure-activity relationships to advance, will require a better understanding of molecular reactivity. A rapid and inexpensive spectrophotometric assay for determining the reactive to glutathione (GSH) was developed and used to determine GSH reactivity (reactGSH) data for 21 aliphatic derivatives of esters, ketones and aldehydes. From these data, a series of structure-activity relationships were evaluated. The structure feature associated with reactGSH was an acetylenic or olefinic moiety conjugated to a carbonyl group (i.e. polarized alpha,beta-unsaturation). This structure conveys the capacity to undergo a covalent interaction with the thiol group of cysteine (i.e. Michael- addition). Quantitatively reactGSH of the alpha,beta-unsaturated carbonyl compounds is reliant upon the specific molecular structure with several tendencies observed. Specifically, it was noted that for alpha,beta-unsaturated carbonyl compounds: (1) the acetylenic-substituted derivatives were more reactive than the corresponding olefinic-substituted ones; (2) terminal vinyl-substituted derivatives was more reactive than the internal vinylene-substituted ones; (3) methyl substitution on the vinyl carbon atoms diminishes reactivity and methyl-substitution on the carbon atom farthest from the carbonyl group causes a larger reduction; (4) derivatives with carbon-carbon double bond on the end of the molecule (i.e. vinyl ketone) were more reactive than one with the carbon-oxygen bond at the end of the molecule (i.e. aldehyde) and (5) the ester with an additional unsaturated vinyl groups were more reactive than the derivative having an unsaturated ethyl group.

A computer-assisted, goal-oriented psychiatric progress note system.

The authors describe a computer system that develops a structured progress note for inclusion in the medical record. The progress note system reflects a goal-oriented patient treatment process and also provides for retrospective analysis of progress note information to accommodate research and review objectives. The system, which has met with a high degree of clinician acceptance, has resulted in improved case documentation, more timely and comprehensive notes, a higher level of objectivity, and a considerable reduction in the time required to organize and record progress note data.

Transperineal percutaneous iridium-192 implant of the prostate.

Interstitial implantation of radioisotopes has become an increasingly popular modality for the management of localized adenocarcinoma of the prostate. Despite the recognized disadvantages, including technical difficulties of accurate seed placement, uncorrectable dose, inhomogeneities in implant volume, limitations in the range of irradiation, and radiation exposure to personnel handling active sources, permanent implantation of either iodine-125 or gold-198 seeds has been widely advocated. A technique of transperineal implantation with afterloading that circumvents many of the problems associated with permanent types of implants is described. Three thousand rad of external beam irradiation was administered three weeks after the implant. Twenty-five patients with clinically localized adenocarcinoma of the prostate were treated with excellent normal tissue tolerance and no major complications. This technique offers excellent control over the implant volume, dose distribution, and radiation exposure to personnel.

Evaluation of a fiber optic immunosensor for quantitating cocaine in coca leaf extracts.

A fiber optic evanescent fluoroimmunosensor was used to rapidly detect and quantitate coca alkaloids as cocaine equivalents in leaf extracts of five Erythroxylum species. A monoclonal antibody (mAb) made against benzoylecgonine (BE), a major metabolite of cocaine, was immobilized covalently on quartz fibers and used as the biological sensing element in the portable fluorometer. Benzoylecgonine-fluorescein (BE-FL) was used as the optical signal generator when it bound to the fiber. If present, cocaine competed for the mAb and interfered with the binding of BE-FL, thereby reducing the fluorescence transmitted by the fiber. Calibration curves were prepared by measuring (over 30 s) the rates of fluorescence increase in the absence, or presence of cocaine. Ethanol or acid extracts of dry coca leaves were assayed by this fiber optic biosensor, gas chromatography and a fluorescent polarization immune assay. Biosensor values of cocaine content of leaves from five Erythroxylum species were not significantly different from gas chromatography values, but had higher variance. The biosensor assay was rapid and did not require cleanup of the crude leaf extracts. Cocaine in acid extracts was reduced significantly after 4 weeks at 23 degrees C and after 3 weeks at 37 degrees C. Fibers (mAb-coated), stored at 37 degrees C in phosphate-buffered solution (0.02% NaN3), gave stable responses for 14 days.

Quantitation of 211At in small volumes for evaluation of targeted radiotherapy in animal models.

We have evaluated SPECT and two planar imaging methods, geometric mean (GM) and buildup factor (BF), for their potential to quantitate in vivo 211At distributions in rat spinal subarachnoid spaces using phantom studies. The use of medium-energy collimators and the small diameter (3 mm) of the subarachnoid space complicate quantitation. Net activities from distributions in various backgrounds were obtained using a large region of interest with background subtraction. Results showed quantitation accuracy within 10% for SPECT and BF in low backgrounds increasing to 25% at higher background levels while GM errors ranged from 20 to 45%. We have also obtained images of [211At]astatide distributions, administered intrathecally, in rats.