Stereotactic body radiotherapy for the treatment of oligometastatic gynecological malignancy in the abdomen and pelvis: A single-institution experience.

PURPOSE/OBJECTIVES: Metastasis-directed therapy with stereotactic body radiotherapy (SBRT) in the setting of oligometastatic disease is a rapidly evolving paradigm given ongoing improvements in systemic therapies and diagnostic modalities. However, SBRT to targets in the abdomen and pelvis is historically associated with concerns about toxicity. The purpose of this study was to evaluate the safety and efficacy of SBRT to the abdomen and pelvis for women with oligometastases from primary gynecological tumors. MATERIALS/METHODS: From our IRB-approved registry, all patients who were treated with SBRT between 2014 and 2020 were identified. Oligometastatic disease was defined as 1 to 5 discrete foci of clinical metastasis radiographically diagnosed by positron emission tomography (PET) and/or computerized tomography (CT) imaging. The primary endpoint was local control at 12 months. Local and distant control rates were estimated using the Kaplan-Meier method. Time intervals for development of local progression and distant progression were calculated based on follow up visits with re-staging imaging. Acute and late toxicity outcomes were determined based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: We identified 34 women with 43 treated lesions. Median age was 68 years (range 32-82), and median follow up time was 12 months (range 0.2-54.0). Most common primary tumor sites were ovarian (n=12), uterine (n=11), and cervical (n=7). Median number of previous lines of systemic therapy agents at time of SBRT was 2 (range 0-10). Overall, SBRT was delivered to 1 focus of oligometastasis in 29 cases, 2 foci in 2 cases, 3 foci in 2 cases, and 4 foci in 1 case. All patients were treated comprehensively with SBRT to all sites of oligometastasis. Median prescription dose was 24 Gy (range 18-54 Gy) in 3 fractions (range 3-6) to a median prescription isodose line of 83.5% (range 52-95). Local control by lesion at 12 and 24 months was 92.5% for both time points. Local failure was observed in three treated sites among two patients, two of which were at 11 months in one patient, and the other at 30 months. Systemic control rate was 60.2% at 12 months. Overall survival at 12 and 24 months was 85% and 70.2%, respectively. Acute grade 2 toxicities included nausea (n=3), and there were no grade > 3 acute toxicities. Late grade 1 toxicities included diarrhea (n=1) and fatigue (n=1), and there were no grade > 2 toxicities. CONCLUSION: SBRT to oligometastatic gynecologic malignancies in the abdomen and pelvis is feasible with encouraging preliminary safety and local control outcomes. This approach is associated with excellent local control and low rates of toxicity during our follow-up interval. Further investigations into technique, dose-escalation and utilization are warranted.

Weight-HbA1c-insulin-glucose model for describing disease progression of type 2 diabetes.

A previous semi-mechanistic model described changes in fasting serum insulin (FSI), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) in patients with type 2 diabetic mellitus (T2DM) by modeling insulin sensitivity and ß-cell function. It was later suggested that change in body weight could affect insulin sensitivity, which this study evaluated in a population model to describe the disease progression of T2DM. Nonlinear mixed effects modeling was performed on data from 181 obese patients with newly diagnosed T2DM managed with diet and exercise for 67 weeks. Baseline ß-cell function and insulin sensitivity were 61% and 25% of normal, respectively. Management with diet and exercise (mean change in body weight = -4.1 kg) was associated with an increase of insulin sensitivity (30.1%) at the end of the study. Changes in insulin sensitivity were associated with a decrease of FPG (range, 7.8-7.3 mmol/L) and HbA1c (6.7-6.4%). Weight change as an effector on insulin sensitivity was successfully evaluated in a semi-mechanistic population model.

Sleep disturbances in athletic concussion.

BACKGROUND: Sleep disturbances are a common symptom following concussions to include athletic concussion. REVIEW: This review applies literature on sleep following traumatic brain injury and concussion to sport concussions and places these considerations in the context of sleep and athletic performance. It also includes a description of sleep abnormalities in sleep duration, quality and timing as well as recommended treatment approaches. Finally, it includes a brief discussion of emerging paradigms of sleep and concussion recovery.

Quality of alveolar bone--Structure-dependent material properties and design of a novel measurement technique.

The evidence for the efficiency of clinical methods used to assess the quality of alveolar bone in terms of a density measure prior to and during dental implant surgery is limited. The aim of this paper is to describe the biomechanical background which can be used as a basis for determining the bone quality by measuring the elastic properties of the bone and to design a novel device for the determination of the bone quality during dental implant surgery. Applying material mechanical equations for porous and cellular structured models, the elastic material properties (modulus of elasticity) of cellular and cortical bone as porous structures were approximated over the whole range of relative bone mineral density of trabecular and cortical bone. Based on a circular disc with a central hole reflecting a horizontal cross-section of an implant socket, the mechanical effects of expanding the central hole were studied. Subsequently, the clinical situation of a socket prepared for the placement of a dental implant (depth: 10 mm; diameter 3.5 mm) was simulated using three-dimensional (3D) finite element analysis. A loading device (thickness: 3.5 mm) was placed in the trabecular part of the socket and expanded, while the resulting pressure was recorded and used for the calculation of an elastic modulus. Finite element analysis revealed that it was possible to estimate the bone quality by applying the measurement technique proposed. Maximum deviations of 6% of the experimentally determined elastic modulus from the setpoint elastic modulus were found. Measuring the internal pressure in a drill hole, e.g., in an implant socket caused by a defined expansion of a rotational symmetric loading device, could be used for establishing a clinically meaningful test system for the objective classification of alveolar bone.

Measuring circadian advantage in Major League Baseball: a 10-year retrospective study.

PURPOSE: The effect of travel on athletic performance has been investigated in previous studies. The purpose of this study was to investigate this effect on game outcome over 10 Major League Baseball (MLB) seasons. METHODS: Using the convention that for every time zone crossed, synchronization requires 1 d, teams were assigned a daily number indicating the number of days away from circadian resynchronization. With these values, wins and losses for all games could be analyzed based on circadian values. RESULTS: 19,079 of the 24,121 games (79.1%) were played between teams at an equal circadian time. The remaining 5,042 games consisted of teams playing at different circadian times. The team with the circadian advantage won 2,620 games (52.0%, P = .005), a winning percentage that exceeded chance but was a smaller effect than home field advantage (53.7%, P < .0001). When teams held a 1-h circadian advantage, winning percentage was 51.7% (1,903-1,781). Winning percentage with a 2-h advantage was 51.8% (620-578) but increased to 60.6% (97-63) with a 3-h advantage (3-h advantage > 2-hadvantage = 1-h advantage, P = .036). Direction of advantage showed teams traveling from Western time zones to Eastern time zones were more likely to win (winning percentage = .530) than teams traveling from Eastern time zones to Western time zones (winning percentage = .509) with a winning odds 1.14 (P = .027). CONCLUSION: These results suggest that in the same way home field advantage influences likelihood of success, so too does the magnitude and direction of circadian advantage. Teams with greater circadian advantage were more likely to win.

Different bone loading patterns due to fixation of three-unit and five-unit implant prostheses.

BACKGROUND: It has been considered that implant prostheses ought to display passive fit. The objective of this finite element analysis (FEA) was to simulate the bone loading resulting from the fixation of implant-supported three and five-unit fixed partial dentures (FPDs). METHODS: Based on a patient case, six different FPD-groups were fabricated using either two or three implants for support. Strain gauges on the pontics of the prostheses were used for in vivo measurements. Based on the values obtained, bone loading models were simulated using three-dimensional finite element analysis and the results obtained were represented as von Mises equivalent stress. RESULTS: The mean strain (epsilon) values ranged from 15 micro epsilon to 170 micro epsilon for the three-unit FPDs and from 32 micro epsilon to 302 micro epsilon for the five-unit FPDs. FEA revealed von Mises stresses up to 30 MPa in the cortical area, while in trabecular bone values up to 5 MPa were observed. Static implant loading of similar magnitude can be provoked through 200 N axial load. CONCLUSIONS: Although the in vivo measured strain levels (epsilon) were of higher magnitude for the five-unit prostheses, FEA revealed bone loading of comparable magnitude for both three- and five-unit FPDs. Multi-unit prostheses may demonstrate greater inaccuracies compared with single implant restorations, but due to the absence of moment loading the multi-implant configuration appears to compensate for the higher strain development.

[A rare cause of subacute parotitis. The pathogenetic role of crystals from an infarcted Whartin's tumour?]. / Seltene Ursache einer subakuten Parotitis. Pathogenetische Rolle von Kristallen aus infarziertem Warthin-Tumor?

The etiology of a subacute inflammatory swelling in the area of the right parotid gland in a 62-years old man could not be resolved clinically. The histomorphological examination of the surgical specimen showed an intraglandular area of predominantly chronic histiocytic inflammation with foreign body reaction in the intimate neighbourhood of a small, subtotally infarcted Warthin's tumour. Not birefringent spindle-shaped crystals could be demonstrated both within the parotitis or intraluminally in vital parts of the Warthin's tumour. In terms of the possible causes of the severe intraglandular inflammation, all arguments favour a primary infarction of the Warthin's tumour with the release of intraluminal preformed crystals which secondarily induce a massive inflammation with foreign body reaction, corresponding to the clinical presentation of a subacute parotitis.

A time-dependent healing function for immediate loaded implants.

Current interest in immediate dental implant loading has grown due to a number of clinical advantages this treatment modality offers. To obtain a deeper insight into the changing mechanical properties during the healing phase, results from removal torque tests are used in a biomechanical model. The ultimate removal torques, which depend on healing time, are described by a time-dependent healing function. The bone behavior is modeled using an elastic law with damage. The evolution of damage is represented with an incremental equation with an initial damage value and two material parameters. The nonlinear relationship between the torque and the angle of rotation up to the ultimate torque can be calculated. By changing the elastic parameter in the elastic damage law, the remodeling process can be characterized. In a further step, the elastic parameters and the limits for shear stress from the biomechanical model for the removal torque will be used in an FE analysis in order to obtain information on the axial loading limits of a dental implant at different healing times.

Amphetamine-induced chorea in attention deficit-hyperactivity disorder.

Attention deficit-hyperactivity disorder (ADHD) is treated frequently with stimulants in both children and adults. While tics are occasional complications of stimulant therapy, chorea is reported rarely. We describe an adult ADHD patient who developed chorea upon dose escalation of mixed amphetamine salts, which resolved on discontinuation of the drug.

The influence of dressings and ointments on the qualitative and quantitative evaluation of burn wounds by ICG video-angiography: an experimental setup.

Burn wound depth is difficult to determine. Even for experienced investigators the exact differentiation between superficial and deep dermal burns is not always possible. Therefore, methods for objective and reproducible measurements estimating the depth of burn wounds are of great clinical interest. One technique that appears to be able to differentiate between superficial and deep dermal burn wounds is ICG video-angiography. Since burn wounds are often covered with dressings and ointments or soiled with blood, it is necessary to evaluate the influence of these substances on ICG video-angiography and its performance as a measurement method. The most commonly used ointments and dressings were tested. All studied substances had a massive influence on ICG video-angiography and its measurements. They caused decreases by absorption of up to 63 +/- 36% and thereby falsely reported deeper burn wounds. The results of this study, suggest that in clinical practice, all dressings, ointments and blood should be completely removed at least 10 min prior to measurement by ICG video-angiography to gain exact and reproducible results.

Use of subatmospheric pressure therapy to prevent burn wound progression in human: first experiences.

Thermal trauma causes two different types of injuries within the burn wound. First, an immediate and irreversible injury, and, second, a delayed and partly reversible injury. It is a very common observation in burned patients that areas that initially seemed to be partial thickness burns have to be regarded as full thickness within the next day or days. The impairment of blood flow within the zone of stasis is due to the impairment of the vascular patency at the microvascular level. This progression is closely correlated to the degree of oedema formation. The aim of the study was to demonstrate that applied, controlled subatmospheric pressure is useful to prevent the progression of partial thickness burn injuries. Therefore, seven patients (mean age, 44.2 years; S.D., 22.4 years) with bilateral partial thickness hand burns were included into this treatment protocol. The more intense injured hand was treated with controlled applied subatmospheric pressure (V.A.C. (ATS)), the other and less injured hand conservatively by use of silver sulphadiazine creme. In the V.A.C.-treated hand a massive hyperperfusion was observed, being a possible reason for the prevention of burn progression. Moreover, a noteworthy amount of fluid was removed from the burn wound and a clinically obvious oedema reduction was observed in comparison to the contralateral side. In summary, we are of the opinion, that patients with partial thickness or mixed thickness burn may benefit from the application of subatmospheric pressure by reducing oedema formation and increasing perfusion.

Indocyanine green video angiographies help to identify burns requiring operation.

The key decision in the treatment of thermal injuries is the determination of the depth of the burn wound and the resultant decision on treatment options. The trend in the treatment of deep dermal and full thickness burns is toward very early excision and grafting to reduce the risk of infection, decrease scar formation, shorten hospital stay, and thereby reducing costs. Traditionally, this has involved serial clinical examinations, which involves primarily subjective judgment. Various objective examination techniques, supplementing the clinical diagnosis, have been suggested, but none has yet achieved widespread clinical acceptance. It has frequently been postulated that the blood flow in injured tissue indicates the extent of tissue damage. In this study, the clinical and scientific impact of indocyanine green (ICG) video angiography was tested in 20 patients. A wide range of depth of injury and etiology was included and analyzed. In all cases considered, video angiography was possible. The measurements and observations correlated well with the actual burn depth, which was assessed clinically (pre- and intraoperative assessment) and histologically (biopsies). In conclusion, ICG video angiography seems to be a practical method to describe vascular patency in a burn wound. The results indicate that ICG fluorescence angiography is a practical, accurate, and effective adjunct to clinical methods for estimating burn wound depth and thereby to assist in the rational assessment of treatment options. Furthermore, it allows an objective, qualitative and quantitative observation of the dynamic changes in burn wound depth, which are observed during the acute post-burn period, thereby indicating optimal timing of the first operation.

Hydrocortisone improved haemodynamics and fluid requirement in surviving but not non-surviving of severely burned patients.

Recent studies have shown that administration of hydrocortisone may lead to a reduction of catecholamines and to an improved outcome in septic patients. However, there are no data on the use of hydrocortisone in burn patients although in these patients reduction of vasopressors might be even more crucial for outcome due to improvement of skin perfusion. This study presents the first results on the impact of hydrocortisone administration in norepinephrine dependent severely burned patients. In a prospective cohort study fourteen consecutive severely burned patients received, 12h after norepinephrine dependency, a hydrocortisone bolus of 100mg followed by 0.18mg/(kgh) hydrocortisone. The course of the necessary norepinephrine dose, as well as the fluid balance was documented 12h prior and after the first dosage of hydrocortisone. Statistical analysis showed an unexpected increase of the required norepinephrine dosage. A statistical post hoc evaluation of surviving and non-surviving patients revealed a significant increase of norepinephrine in non-survivors whereas in survivors it was possible to reduce norepinephrine significantly. Furthermore, the median fluid requirement of surviving patients could be significantly reduced whereas in the group of non-survivors there was no change of volume needed. Our data suggests that hydrocortisone might be useful in selected patients with severe burn injuries. However, patients not responding to hydrocortisone administrations seem to have a poor prognosis. Our findings are in contrast to previously published data on septic patients, in whom hydrocortisone administration resulted in a reduction of norepinephrine. In burned patients the severity of trauma seems to have more profound influence on the pathophysiological mechanism of sepsis. Due to the high number of non-responders, the potential immune suppression and impaired wound healing caused by the side effects of hydrocortisone, further selection criteria seem to be necessary. A short ACTH-test might be considered prior to hydrocortisone administration to select patients who might benefit from this therapy. In summary, further prospective controlled studies will be necessary to establish hydrocortisone in the routine therapy of severely burned patients.

A comparison of propofol and sevoflurane anaesthesia: effects on aortic blood flow velocity and middle cerebral artery blood flow velocity.

We compared systemic (aortic) blood flow and cerebral blood flow velocity in 30 patients randomly allocated to receive either propofol or sevoflurane anaesthesia. Cerebral blood flow velocity (CBFv) was measured in the middle cerebral artery using transcranial Doppler. Systemic blood flow velocity (SBFv) was measured in the aorta using transthoracic Doppler sonography at the level of the aortic valve. Bispectral index (BIS) was used to measure the depth of anaesthesia. Measurements were made in the awake patient and repeated during propofol or sevoflurane anaesthesia, with BIS measurements of 40-50. The effects of SBFv on CBFv were estimated by calculating the cerebral/systemic blood flow velocity-index (CsvI). A CsvI value of 100 indicating a 1 : 1 relationship between CBFv and SBFv. The results demonstrated that propofol anaesthesia produced a significantly greater reduction in CsvI than did sevoflurane anaesthesia [propofol: 60 (19); sevoflurane: 83 (16), p = 0.009, t-test]. This suggests a direct reduction in CBFv independent of SBFv during propofol anaesthesia. The greater reduction of CBFv occurring during propofol anaesthesia may be due to lower cerebral metabolic demand compared with sevoflurane anaesthesia at comparable depths of anaesthesia.

Determination of the 8B neutrino spectrum.

We have measured the total energy of the alpha particles following the beta decay of 8B by implanting 8B into a planar silicon surface barrier detector. Calibration was performed using alpha particles following the beta decay of 20Na, similarly implanted. The alpha spectrum is used to infer the 8B neutrino spectrum which is an important input in the interpretation of experiments that detect energetic neutrinos from the Sun. The alpha spectrum reported here is in disagreement with the previous best measurement which used two detectors in coincidence.

Acquisition of expertise on a difficult perceptual-motor task by an amnesic patient.

While numerous studies have reported learning of perceptual-motor skills by amnesic patients, few if any have documented the eventual acquisition of expertise on a given task. This paper recounts the learning of the computer game Tetris by a hippocampal amnesic, whose acquisition of the task in a formal evaluation was somewhat slower than that of a comparison group, but who after many hours of self-paced practice achieved expert-level play.