To determine how intraoperative microelectrode recordings (MER) and intraoperative lead placement acutely influence tremor, rigidity, and bradykinesia. Secondarily, to evaluate whether the longevity ...of the MER and lead placement effects were influenced by target location (subthalamic nucleus (STN) or globus pallidus interna (GPi)).
Currently most groups who perform deep brain stimulation (DBS) for Parkinson disease (PD) use MER, as well as macrostimulation (test stimulation), to refine DBS lead position. Following MER and/or test stimulation, however, there may be a resultant "collision/implantation" or "microlesion" effect, thought to result from disruption of cells and/or fibres within the penetrated region. These effects have not been carefully quantified.
47 consecutive patients with PD undergoing unilateral DBS for PD (STN or GPi DBS) were evaluated. Motor function was measured at six time points with a modified motor Unified Parkinson Disease Rating Scale (UPDRS): (1) preoperatively, (2) immediately after MER, (3) immediately after lead implantation/collision, (4) 4 months following surgery-off medications, on DBS (12 h medication washout), (5) 6 months postoperatively-off medication and off DBS (12 h washout) and (6) 6 months-on medication and off DBS (12 h washout).
Significant improvements in motor scores (p<0.05) (tremor, rigidity, bradykinesia) were observed as a result of MER and lead placement. The improvements were similar in magnitude to what was observed at 4 and 6 months post-DBS following programming and medication optimisation. When washed out (medications and DBS) for 12 h, UPDRS motor scores were still improved compared with preoperative testing. There was a larger improvement in STN compared with GPi following MER (p<0.05) and a trend for significance following lead placement (p<0.08) but long term outcome was similar.
This study demonstrated significant acute intraoperative penetration effects resulting from MER and lead placement/collision in PD. Clinicians rating patients in the operating suite should be aware of these effects, and should consider pre- and post-lead placement rating scales prior to activating DBS. The collision/implantation effects were greater intraoperatively with STN compared with GPi, and with greater disease duration there was a larger effect.
•Study evaluating postoperative course after TORS oropharyngeal resection.•Clinical trial patients receiving deescalated adjuvant therapy for HPV(+)OPSCC.•Patients had acceptable post-operative ...bleeding rates requiring intervention (4.6%)•There were very low rates of postoperative complication.
Dose de-escalation of adjuvant therapy (DART) in patients with HPV(+)OPSCC was investigated in two prospective Phase II and III clinical trials (MC1273 and MC1675). We report the 30-day morbidity and mortality associated with primary TORS resection in patients enrolled in these trials.
Patients with HPV(+)OPSCC, who underwent TORS resection between 2013 and 2020 were considered in this analysis. The severity of postoperative transoral bleeding was graded using both the Hinni Grade (HG) transoral surgery bleeding scale and the Common Terminology for Adverse Events (CTCAE) v5.0. Post-surgical complications within 30 days of surgery, as well as rates of tracheostomy, PEG and nasogastric tube placement.
219 patients were included. A total of 7 (3.2 %) patients had a tracheostomy placed at the time of surgery, and all were decannulated within 26 days (median: 5, range: 2–26). There were 33 (15.1 %) returns to the emergency department (ED) with 10 (4.6 %) patients requiring readmission. Using the HG scale, 10 (4.6 %) patients experienced ≥ Grade 3 bleeding with no Grade 5 or 6 bleeds. In contrast, using the CTCAE scale, 15 patients (6.8 %) experienced ≥ Grade 3 bleeding with no Grade 5 bleeds. There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage.
TORS for HPV(+)OPSCC in carefully selected patients at a high volume center was associated with low morbidity and mortality.
The physiological response of the preruminant calf to sustained exposure to moderate cold has not been studied extensively. Effects of cold on growth performance and health of preruminant calves as ...well as functional measures of energy metabolism, fat-soluble vitamin, and immune responsiveness were evaluated in the present study. Calves, 3 to 10 d of age, were assigned randomly to cold (n = 14) or warm (n = 15) indoor environments. Temperatures in the cold environment averaged 4.7°C during the study. Frequent wetting of the environment and the calves was used to augment effects of the cold environment. Temperatures in the warm environment averaged 15.5°C during the study. There was no attempt to increase the humidity in the warm environment. Preventative medications or vaccinations that might influence disease resistance were not administered. Nonmedicated milk replacer (20% crude protein and 20% fat fed at 0.45 kg/d) and a nonmedicated starter grain fed ad libitum were fed to all calves. Relative humidity was, on average, almost 10% higher in the cold environment. Warm-environment calves were moderately healthier (i.e., lower respiratory scores) and required less antibiotics. Scour scores, days scouring, and electrolyte costs, however, were unaffected by environmental temperature. Growth rates were comparable in warm and cold environments, although cold-environment calves consumed more starter grain and had lower blood glucose and higher blood nonesterified fatty acid concentrations. The nonesterified fatty acid and glucose values for cold-stressed calves, however, did not differ sufficiently from normal values to categorize these calves as being in a state of negative-energy balance. Levels of fat-soluble vitamin, antibody, tumor necrosis factor-α, and haptoglobin were unaffected by sustained exposure to moderate cold. These results support the contention that successful adaptation of the dairy calf to cold is dependent upon the availability of adequate nutrition.
In this era of patient-centered, outcomes-driven and adaptive radiotherapy, deep learning is now being successfully applied to tackle imaging-related workflow bottlenecks such as autosegmentation and ...dose planning. These applications typically require supervised learning approaches enabled by relatively large, curated radiotherapy datasets which are highly reflective of the contemporary standard of care. However, little has been previously published describing technical infrastructure, recommendations, methods or standards for radiotherapy dataset curation in a holistic fashion. Our radiation oncology department has recently embarked on a large-scale project in partnership with an external partner to develop deep-learning-based tools to assist with our radiotherapy workflow, beginning with autosegmentation of organs-at-risk. This project will require thousands of carefully curated radiotherapy datasets comprising all body sites we routinely treat with radiotherapy. Given such a large project scope, we have approached the need for dataset curation rigorously, with an aim towards building infrastructure that is compatible with efficiency, automation and scalability. Focusing on our first use-case pertaining to head and neck cancer, we describe our developed infrastructure and novel methods applied to radiotherapy dataset curation, inclusive of personnel and workflow organization, dataset selection, expert organ-at-risk segmentation, quality assurance, patient de-identification, data archival and transfer. Over the course of approximately 13 months, our expert multidisciplinary team generated 490 curated head and neck radiotherapy datasets. This task required approximately 6000 human-expert hours in total (not including planning and infrastructure development time). This infrastructure continues to evolve and will support ongoing and future project efforts.
A multi-institutional, prospective, randomized trial was undertaken in patients with advanced head-and-neck squamous cell carcinoma to address (1) the validity of using pathologic risk features, ...established from a previous study, to determine the need for, and dose of, postoperative radiotherapy (PORT); (2) the impact of accelerating PORT using a concomitant boost schedule; and (3) the importance of the overall combined treatment duration on the treatment outcome.
Of 288 consecutive patients with advanced disease registered preoperatively, 213 fulfilled the trial criteria and went on to receive therapy predicated on a set of pathologic risk features: no PORT for the low-risk group (n = 31); 57.6 Gy during 6.5 weeks for the intermediate-risk group (n = 31); and, by random assignment, 63 Gy during 5 weeks (n = 76) or 7 weeks (n = 75) for the high-risk group. Patients were irradiated with standard techniques appropriate to the site of disease and likely areas of spread. The study end points were locoregional control (LRC), survival, and morbidity.
Patients with low or intermediate risks had significantly higher LRC and survival rates than those with high-risk features (p = 0.003 and p = 0.0001, respectively), despite receiving no PORT or lower dose PORT, respectively. For high-risk patients, a trend toward higher LRC and survival rates was noted when PORT was delivered in 5 rather than 7 weeks. A prolonged interval between surgery and PORT in the 7-week schedule was associated with significantly lower LRC (p = 0.03) and survival (p = 0.01) rates. Consequently, the cumulative duration of combined therapy had a significant impact on the LRC (p = 0.005) and survival (p = 0.03) rates. A 2-week reduction in the PORT duration by using the concomitant boost technique did not increase the late treatment toxicity.
This Phase III trial established the power of risk assessment using pathologic features in determining the need for, and dose of, PORT in patients with advanced head-and-neck squamous cell cancer in a prospective, multi-institutional setting. It also revealed the impact of the overall treatment time in the combination of surgery and PORT on the outcome in high-risk patients and showed that PORT acceleration without a reduction in dose by a concomitant boost regimen did not increase the late complication rate. These findings emphasize the importance of coordinated interdisciplinary care in the delivery of combined surgery and RT.
To determine local control (LC) and complication rates for patients with intracranial meningiomas who underwent radiosurgery.
One hundred ninety consecutive patients with 206 meningiomas underwent ...radiosurgery between 1990 and 1998. One hundred forty-seven tumors (77%) involved the cranial base. The median age at the time of radiosurgery was 58 years (range, 20-90 yr). There were 126 female patients (66%). One hundred twelve patients (59%) had undergone one or more previous operations (median, 1; range, 1-5). Twenty-two patients (12%) had either atypical (n = 13) or malignant (n = 9) tumors. The median prescription isodose volume was 8.2 cm(3) (range, 0.5-50.5 cm(3)), and the median tumor margin dose was 16 Gy (range, 12-36 Gy). The median imaging and clinical follow-up periods were 40 and 47 months, respectively.
Overall survival rates for the entire cohort at 5 and 7 years were 82 and 82%, respectively; cause-specific survival rates at 5 and 7 years were 94 and 92%, respectively. The cause-specific survival rates at 5 years for patients with benign, atypical, and malignant tumors were 100, 76, and 0%, respectively (P < 0.0001). The 5-year LC rate was 89%, with 114 tumors (56%) decreasing in size. LC rates were correlated with tumor histological features (P < 0.0001); patients with benign tumors exhibited a 5-year LC rate of 93%, compared with 68 and 0% for patients with atypical or malignant meningiomas, respectively. No correlation was observed between radiation dose and LC rate. Twenty-four patients (13%) experienced treatment-related complications, including cranial nerve deficits (8%), symptomatic parenchymal changes (3%), internal carotid artery stenosis (1%), and symptomatic cyst formation (1%). Only six patients (3%) exhibited decreases in functional status that were directly related to radiosurgery. Tumor volume, tumor margin dose, or previous radiotherapy was not associated with the development of radiation-related complications.
Radiosurgery is an effective management strategy for many patients with meningiomas. Patients with atypical or malignant tumors exhibit high recurrence rates despite the use of radiosurgery, and these patients continue to exhibit worse cause-specific survival rates despite aggressive treatment, including surgery, external-beam radiotherapy, and radiosurgery. Further study is needed to determine the tumor control and complication rates 10 years or more after meningioma radiosurgery.
Participants of the Multiethnic Cohort Study in Hawaii and Los Angeles, California, a representative sample of African-American, Native Hawaiian, Latino, Japanese-American, and White adults, ...completed a baseline questionnaire in 1993-1996 assessing dietary supplement use during the past year as well as demographic, dietary, and other lifestyle factors. Factors associated with supplement use were examined among those who reported an absence of chronic disease (n = 100,196). Use of any of eight supplements at least once per week during the past year ranged from 44% among Hawaiian men to 75% among Japanese-American and White women. Multivitamins were the most frequently reported supplement; 48% of the men and 56% of the women reported regular use. Dietary supplement use was high across all ethnic groups, although levels and length of regular use varied. In all gender-specific ethnic groups, supplement use tended to increase with age, education, physical activity, fruit intake, and dietary fiber intake and to decrease with obesity, smoking, and dietary fat intake. Participants whose lifestyles were healthier were more likely to use dietary supplements. Therefore, it may be difficult to separate the effects of supplement use from other lifestyle factors when studying disease etiology.
To test the hypothesis that increasing the nerve length within the treatment volume for trigeminal neuralgia radiosurgery would improve pain relief.
Eighty-seven patients with typical trigeminal ...neuralgia were randomized to undergo retrogasserian gamma knife radiosurgery (75 Gy maximal dose with 4-mm diameter collimators) using either one (n = 44) or two (n = 43) isocenters. The median follow-up was 26 months (range 1-36).
Pain relief was complete in 57 patients (45 without medication and 12 with low-dose medication), partial in 15, and minimal in another 15 patients. The actuarial rate of obtaining complete pain relief (with or without medication) was 67.7% +/- 5.1%. The pain relief was identical for one- and two-isocenter radiosurgery. Pain relapsed in 30 of 72 responding patients. Facial numbness and mild and severe paresthesias developed in 8, 5, and 1 two-isocenter patients vs. 3, 4, and 0 one-isocenter patients, respectively (p = 0.23). Improved pain relief correlated with younger age (p = 0.025) and fewer prior procedures (p = 0.039) and complications (numbness or paresthesias) correlated with the nerve length irradiated (p = 0.018).
Increasing the treatment volume to include a longer nerve length for trigeminal neuralgia radiosurgery does not significantly improve pain relief but may increase complications.
Effects of growth rate on fat-soluble vitamin and macro- and micromineral concentrations in the circulation of preruminant dairy calves were evaluated. Dietary treatments were designed to achieve 3 ...targeted rates of gain no growth (NG)=0.0 kg/d; low growth (LG)=0.55 kg/d; or high growth (HG)=1.2 kg/d over a 7-wk period. Milk replacer (MR) intakes necessary to achieve these growth rates were estimated using the National Research Council's Nutrient Requirements of Dairy Cattle calf model computer program. All of the calves were fed a 30% crude protein, 20% fat MR reconstituted to 14% dry matter. The diets were formulated to ensure that protein was not a limiting nutrient. No-growth and LG calves were supplemented additionally with vitamins A, D, and E to compensate for treatment differences in dry matter intake relative to the HG calves; however, no attempt was made to adjust mineral intake based on MR consumption. Growth rates for NG (0.11 kg/d), LG (0.58 kg/d), and HG (1.16 kg/d) calves differed during the study. Health was minimally affected by growth rate and this was reflected by comparable and relatively low serum haptoglobin concentrations in all calves during the 7-wk period. Concentrations of serum retinol, 25-(OH)-vitamin D3, and zinc were unaffected by growth rate. The HG calves had lower RRR-α-tocopherol concentrations than NG and LG calves at wk 7, suggesting that the increased growth rate of HG calves was associated with increased utilization of vitamin E. Serum concentrations of all vitamins increased with age. Copper, calcium, and phosphorous concentrations in HG calves exceeded those in LG and NG calves during the latter weeks of the study, likely because of increased MR intake by HG calves. Fat-soluble vitamin and mineral concentrations for all treatment groups remained within ranges considered normal for preruminant calves.
The use of stereotactic radiosurgery to treat cerebral cavernous malformations (CMs) is controversial. To evaluate the efficacy and safety of CM radiosurgery, the authors reviewed the experience at ...the Mayo Clinic during the past 10 years.
Seventeen patients underwent radiosurgery for high-surgical-risk CMs in the following sites: thalamus/basal ganglia (four patients), brainstem (12 patients), and corpus callosum (one patient). All patients had experienced at least two documented hemorrhages before undergoing radiosurgery. Stereotactic magnetic resonance (MR) imaging was used for target localization in all cases. The median margin radiation dose was 18 Gy and the median maximum dose was 32 Gy. The median length of follow-up review following radiosurgery was 51 months. The annual hemorrhage rate during the 51 months preceding radiosurgery was 40.1%, compared with 8.8% in the first 2 years following radiosurgery and 2.9% thereafter. In 10 patients (59%) new neurological deficits developed that were associated with regions of increased signal on long-repetition time MR imaging performed a median of 8 months (range 5-16 months) after radiosurgery. Three patients recovered, giving the group a permanent radiation-related morbidity rate of 41%. Compared with 31 patients harboring arteriovenous malformations (AVMs) of sizes and in locations similar to those of the aforementioned CMs, who underwent radiosurgery during the same time period, the patients with CMs were more likely to experience radiation-related complications (any complication, 59% compared with 10%; p < 0.001; permanent complication, 41% compared with 10%; p = 0.02).
It is impossible to conclude that radiosurgery protects patients with CMs against future hemorrhage risk based on the available data, although it appears that some reduction in the bleeding rate occurs after a latency interval of several years. The risk of radiation-related complications after radiosurgery to treat CMs is greater than that found after radiosurgery in AVMs, even when adjusting for lesion size and location and for radiation dose.
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