Randomized Trial of Postoperative Radiation Therapy After Wide Excision of Neurotropic Melanoma of the Head and Neck (RTN2 Trial 01.09).

BACKGROUND: Cutaneous neurotropic melanoma (NM) of the head and neck (H&N) is prone to local relapse, possibly due to difficulties widely excising the tumor. This trial assessed radiation therapy (RT) to the primary site after local excision. METHODS: Participants from 15 international centers were randomized to observation or RT. The participants were required to have microscopically negative excision margins 5 mm wide or wider and no evidence of disease elsewhere. The primary outcome was time to local relapse. The secondary outcomes included time to any recurrence, overall survival (OS), and toxicity. RESULTS: The trial ceased prematurely due to slow recruitment and the COVID-19 pandemic. During 2009-2020, 50 participants were randomized: 23 to observation and 27 to RT. The most common NM subsites were scalp (32%), midface (22%), and lip (20%). The median depth of invasion was 5 mm, and desmoplasia observed in 69%. The median duration from randomization to last contact was 4.8 years. Four participants (8%) experienced local relapse as a first recurrence during the study period: 3 in the observation arm and 1 in the RT arm (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.03-2.76; p = 0.279). No statistically significant difference in time to any relapse or OS was observed. More than 6 months after randomization, grade 3 or greater toxicity was experienced by 10% of the participants in the observation arm and 12.5% of the participants in the RT arm of the study. CONCLUSION: Due to low accrual, the role of adjuvant RT for cutaneous NM of the H&N excised with microscopically negative margins 5 mm wide or wider remains undefined. Its routine use cannot be recommended. Local relapse might be less common than previously anticipated based on retrospective reports.

One-year implant survival following lateral window sinus augmentation using plasma rich in growth factors (PRGF): a retrospective study.

BACKGROUND: The aim of this study was to assess one-year implant survival after lateral window sinus augmentation using PRGF combined with various bone grafting materials. MATERIAL AND METHODS: This was a retrospective chart review and radiographic analysis of patients that had undergone lateral window sinus augmentation with PRGF and had dental implants placed at least 6 months post augmentation. All implants included were followed up for at least one year after placement. Demographic, sinus and implant related characteristics (residual ridge height, sinus membrane perforation, type of graft material, implant length and width and ISQ at placement) were analyzed. RESULTS: A total of 31 patients with 39 sinus augmentations and 48 implants were included. The mean follow up was 22.8 ± 9.9 months. Implant survival was 95.8%, with 2 implants overall failing. Among all the variables assessed, the only one found to be associated with an increased risk for implant failure was the use of xenograft as bone grafting material in the sinus. CONCLUSIONS: Within the limitations of this study, dental implants placed in maxillary sinuses grafted with PRGF in combination with bone grafting materials, exhibit high implant survival rates after at least one year follow up.

Diabetes mellitus and extrapulmonary tuberculosis: site distribution and risk of mortality.

Scarce data exist on the relationship between diabetes and extrapulmonary tuberculosis (EPTB). We evaluated whether diabetes impacts site of TB and risk of death in patients with EPTB. We evaluated a cohort of TB cases from the state of Georgia between 2009 and 2012. Patients aged ⩾16 years were classified by diabetes status according to medical records. Site of EPTB was determined by culture and/or state TB classification. Death was defined by all-cause mortality. Of 1325 eligible reported TB cases, 369 (27·8%) had any EPTB including 258 (19·5%) with only EPTB and 111 (8·4%) with pulmonary TB and EPTB. Of all TB cases, 158 had diabetes (11·9%). In multivariable analysis, the odds of any EPTB was similar in patients with and without diabetes [adjusted odds ratio 1·04, 95% confidence interval (CI) 0·70-1·56]. The risk of death was 23·8% in patients with EPTB and diabetes vs. 9·8% in those with no diabetes (P < 0·01); after adjusting for covariates the difference was not significant (aRR 1·19, 95% CI 0·54-2·63). Diabetes was common in patients with EPTB and risk of death was high. Improved understanding of the relationship between diabetes and EPTB is critical to determine the extent that diabetes affects TB diagnosis and clinical management.

A systematic review of non-surgical treatments for lentigo maligna.

Lentigo maligna (LM) is the most common melanocytic malignancy of the head and neck. If left untreated, LM can progress to lentigo maligna melanoma (LMM). Complete surgical excision is the gold standard for treatment, however, due to the location, size, and advanced age of patients, surgery is not always acceptable. As a result, there is ongoing interest in alternative, less invasive treatment modalities. The objective was to provide a structured review of key literature reporting the use of radiotherapy, imiquimod and laser therapy for the management of LM in patients where surgical resection is prohibited. An independent review was conducted following a comprehensive search of the National Library of Medicine using MEDLINE and PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases. Data were presented in tabular format, and crude data pooled to calculate mean recurrence rates for each therapy. 29 studies met the inclusion criteria: radiotherapy 10; topical imiquimod 10; laser therapies 9. Radiotherapy demostrated recurrence rates of up to 31% (mean 11.5%), with follow-up durations of 1-96 months. Topical imiquimod recurrence rates were up to 50% (mean 24.5%), with follow-up durations of 2-49 months. Laser therapy yielded recurrence rates of up to 100% (mean 34.4%), and follow-up durations of 8-78 months. in each of the treatment series the I(2) value measuring statistical heterogeneity exceeded the accepted threshold of 50% and as such a meta-analysis of included data were inappropriate. For non-surgical patients with LM, radiotherapy and topical imiquimod were efficacious treatments. Radiotherapy produced superior complete response rates and fewer recurrences than imiquimod although both are promising non-invasive modalities. There was no consistent body of evidence regarding laser therapy although response rates of up to 100% were reported in low quality studies. A prospective comparative trial is indicated and would provide accurate data on the long-term efficacy and overall utility of these treatments.

Phase II study of single-agent panitumumab in patients with incurable cutaneous squamous cell carcinoma.

BACKGROUND: Although advanced cutaneous squamous cell carcinoma (CSCC) is quite common, there are few prospective trials regarding its optimal management. This study evaluated the efficacy and safety of single-agent panitumumab in the treatment of patients with CSCC not suitable for local therapy. PATIENTS AND METHODS: Sixteen patients received single-agent panitumumab at a dose of 6 mg/kg repeated every 2 weeks for a minimum of three cycles and continued until progression, a maximum of nine cycles or dose-limiting toxicity. The primary end point was the best overall response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) criteria. Secondary end points included evaluation of safety, toxicity and progression-free survival (PFS). RESULTS: Between May 2010 and May 2012, 16 patients were recruited. Fourteen patients were male and the median age was 68 years. Fifteen patients had locoregionally advanced or recurrent disease with 14 patients receiving previous radiotherapy and 7 receiving previous cytotoxic chemotherapy. The best ORR [partial (PR) or complete response (CR)] was 31% (3/16 PR, 2/16 CR) with a further 6 of 16 patients achieving SD. The median PFS and overall survival were 8 and 11 months respectively. Grade 3 or 4 events were observed in five patients (four being skin toxicity) with one patient ceasing due to skin toxicity. With a median follow-up of 24 months, 10 patients died due to progressive disease, 6 are alive, one patient with no evidence of disease at the time of analysis. CONCLUSIONS: Single-agent panitumumab is safe and effective in the management of patients with advanced CSCC even in a previously extensively pre-treated cohort.

Kidney paired donation: a payer perspective.

Kidney transplantation is the most cost-effective and clinically effective form of renal replacement therapy. Due to long wait times for deceased donors, kidney transplantation is not available to many patients with incompatible living donors. Increased access to kidney transplantation is a shared goal that can be achieved through kidney paired donation (KPD). A single, national system of KPD administered to a set of clinical and ethical standards determined by a consensus of stakeholders including recipients, donors, providers, payers and the United States federal government will provide the best opportunity to offer kidney transplantation to the most people and particularly to those currently unlikely to receive a transplant. We propose that this system will use uniform tissue typing algorithms and a computerized donor and recipient matching program using a national pool of willing donors. The proposed system can be managed best through a single administrative structure that takes advantage of uniform donor evaluation and management with a standardized organ acquisition charge that recognizes that the current lack of standardization contributes to delays in transplantation and payment to programs. This program will use the existing Organ Procurement Organization infrastructure to manage the logistics of organ acquisition, transportation and billing.

Adaptive immunity in the colostrum-deprived calf: response to early vaccination with Mycobacterium bovis strain bacille Calmette Guerin and ovalbumin.

Responses of the newborn calf to vaccination are frequently characterized by marginal antibody (Ab) responses. The present study evaluated effects of colostrum ingestion on the adaptive immune response of the preruminant calf to early vaccination. Colostrum-fed (CF) and colostrum-deprived (CD) calves were vaccinated at 2 d of age with Mycobacterium bovis, Pasteur strain of bacille Calmette Guerin (BCG), and ovalbumin (OVA) to track development of the adaptive immune response during the first 8 wk of life. Dams were also vaccinated with BCG prepartum. At wk 0, serum IgG(1), IgG(2), IgA, and IgM were elevated in CF calves, with IgG(1) predominating. In these calves, IgG(2), IgA, and IgM concentrations decreased with age. The CD calves, in contrast, had very low or undetectable serum immunoglobulin concentrations at wk 0 followed by an age-related increase in IgG(1), IgG(2), and IgM concentrations, suggesting endogenous production of these immunoglobulin classes. Immunoblot and ELISA analyses of Ab response to BCG vaccination indicated that colostrum ingestion was associated with measurable serum anti-mycobacterial Ab in CF calves during the first month postpartum, with substantially lower levels at 7 wk of age. Although mycobacteria-specific Ab was undetectable in CD calves at wk 0, it was present at 4 and 7 wk of age, suggesting that these calves, unlike CF calves, were capable of generating an Ab response to BCG vaccination. Antibody responses of CF and CD calves to vaccination with OVA, an antigen not present in the natural environment of dairy cattle, were of comparable magnitude and characterized by a progressive increase in Ab levels from birth (wk 0) to 7 wk of age. The disparate Ab responses of CF calves to BCG and OVA suggest that maternal antigenic experience or exposure influences Ab responses of the colostrum-fed preruminant calf to early vaccination. Ex vivo, antigen [OVA and M. bovis-derived purified protein derivative (PPDb)]-induced IFN-γ and nitric oxide responses of blood mononuclear cells (PBMC) from CF and CD calves were comparable at wk 0 and wk 7. As expected, responses were very low or nonexistent at wk 0. Responses for all calves were greater at wk 7 than at wk 0, suggesting a colostrum-independent maturation of the cell-mediated immune response capacity of the preruminant calf. The consistently greater proliferative responses of antigen-stimulated T-cell subsets at wk 7 versus wk 0 indicate the development of antigen-specific lymphocyte responses to early vaccination. Total numbers of blood leukocytes as well as numbers of lymphocytes and monocytes were unaffected by colostrum feeding; however, granulocyte numbers were higher in CD than in CF calves at wk 0. Granulocyte numbers decreased and monocyte numbers increased with age in all calves. Within the lymphocyte population, only natural killer (NK(+)) cell percentages were affected by colostrum ingestion, with higher percentages of NK(+) cells in CD calves at wk 0 and wk 7. Antigen-induced proliferation of lymphocyte subsets including IgM(+) cells was unaffected by colostrum ingestion. In conclusion, ingestion of colostrum within hours after birth inhibited the capacity of the calf to produce antigen-specific immunoglobulin (i.e., antibody) in response to vaccination, with little or no effect on cell-mediated immune responses. Although colostrum appeared to block endogenous antibody production, certain B-cell functions were retained. These findings will aid in development of new vaccination strategies for improving health of the preruminant calf.

Outcomes Following Hypofractionated Stereotactic Radiotherapy to the Cavity After Surgery for Melanoma Brain Metastases.

AIMS: Hypofractionated stereotactic radiotherapy (HSRT) to the cavity after surgical resection of brain metastases improves local control. Most reported cohorts include few patients with melanoma, a population known to have high rates of recurrence and neurological death. We aimed to assess outcomes in patients with melanoma brain metastases who received HSRT after surgery at two Australian institutions. MATERIALS AND METHODS: A retrospective analysis was carried out including patients treated between January 2012 and May 2020. HSRT was recommended for patients with melanoma brain metastases at high risk of local recurrence after surgery. Treatment was delivered using appropriately commissioned linear accelerators. Routine follow-up included surveillance magnetic resonance imaging brain every 3 months for at least 2 years. Primary outcomes were overall survival, local control, incidence of radiological radionecrosis and symptomatic radionecrosis. RESULTS: There were 63 cavities identified in 57 patients. The most common HSRT dose prescriptions were 24 Gy in three fractions and 27.5 Gy in five fractions. The median follow-up was 32 months in survivors. Local control was 90% at 1 year, 83% at 2 years and 76% at 3 years. Subtotal brain metastases resection (hazard ratio 12.5; 95% confidence interval 1.4-111; P = 0.0238) was associated with more local recurrence. Overall survival was 64% at 1 year, 45% at 2 years and 40% at 3 years. There were 10 radiological radionecrosis events (16% of cavities) during the study period, with 5% at 1 year and 8% at 2 years after HSRT. The median time to onset of radiological radionecrosis was 21 months (range 6-56). Of these events, three became symptomatic (5%) during the study period at a median time to onset of 26 months (range 21-32). CONCLUSION: Cavity HSRT is associated with high rates of local control in patients with melanoma brain metastases. Subtotal resection strongly predicts for local recurrence after HSRT. Symptomatic radionecrosis occurred in 5% of cavities but increased to 8% of longer-term survivors.

Outcomes and toxicities in oligometastatic patients treated with stereotactic body radiotherapy for adrenal gland metastases: A multi-institutional retrospective study.

BACKGROUND: Studies reporting SBRT outcomes in oligometastatic patients with adrenal gland metastases (AGM) are limited. Herein, we present a multi-institutional analysis of oligometastatic patients treated with SBRT for AGM. MATERIAL/METHODS: The Consortium for Oligometastases Research (CORE) is among the largest retrospective series of patients with oligometastases. Among CORE patients, those treated with SBRT for AGM were included. Clinical and dosimetric data were collected. Adrenal metastatic burden (AMB) was defined as the sum of all adrenal GTV if more than one oligometastases is present.Competing risk analysis was used to estimate actuarial cumulative local recurrence (LR) and widespread progression (WP). Kaplan-Meier method was used to report overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). Treatment related toxicities were also reported. RESULTS: The analysis included 47 patients with 57 adrenal lesions. Median follow-up was 18.2 months. Median LRFS, PFS, and OS were 15.3, 5.3, and 19.1 months, respectively. A minimum PTV dose BED10 > 46 Gy was associated with an improved OS and LRFS. A prescribed BED10 > 70 Gy was an independent predictor of a lower LR probability. AMB>10 cc was an independent predictor of a lower risk for WP. Only one patient developed an acute Grade 3 toxicity consisting of abdominal pain. CONCLUSION: SBRT to AGM achieved a satisfactory local control and OS in oligometastatic patients. High minimum PTV dose and BED10 prescription doses were predictive of improved LR and OS, respectively. Prospective studies are needed to determine comprehensive criteria for patients SBRT eligibility and dosimetric planning.

t10,c12-CLA decreases adiposity in peripubertal mice without dose-related detrimental effects on mammary development, inflammation status, and metabolism.

The trans 10, cis 12-conjugated linoleic acid (10,12-CLA) isomer reduces adiposity in several animal models. In the mouse, however, this effect is associated with adipose tissue inflammation, hyperinsulinemia and hepatic lipid accumulation. Moreover, 10,12-CLA was recently shown to promote mammary ductal hyperplasia and ErbB2/Her2-driven mammary cancer in the mouse. Reasons for detrimental effects of 10,12-CLA on the mouse mammary gland could relate to its effect on the mammary fat pad (MFP), which is essential for normal development. Accordingly, we hypothesized that mammary effects of 10,12-CLA were mediated through the MFP in a dose-dependent manner. Female FVB mice were fed 10,12-CLA at doses of 0%, 0.1%, 0.2%, or 0.5% of the diet from day 24 of age, and effects on mammary development and metabolism were measured on day 49. The 0.5% dose reduced ductal elongation and caused premature alveolar budding. These effects were associated with increased expression of inflammatory markers and genes shown to alter epithelial growth (IGF binding protein-5) and alveolar budding (TNF-α and receptor of activated NF-κB ligand). The 0.5% dose also caused hyperinsulinemia and hepatic lipid accumulation. In contrast, the 0.1% 10,12-CLA dose had no adverse effects on mammary development, metabolic events, and inflammatory responses, but remained effective in decreasing adipose weights and lipogenic gene expression. These results show that a low dose of 10,12-CLA reduces adiposity in the mouse without negative effects on mammary development, inflammation, and metabolism, and suggest that previously reported detrimental effects relate to the use of excessive doses.

Clinical outcomes of adult patients with primary intracranial germinomas treated with low-dose craniospinal radiotherapy and local boost.

The authors document the long term follow up of adult patients with histologically proven primary intracranial germinoma treated with radiotherapy alone using a craniospinal with local boost technique. A retrospective review was conducted on adults diagnosed with intracranial germinoma who received radiotherapy at the Princess Margaret Hospital, Toronto from 1990 to 2007. The study group consisted of 10 males with a median age of 24.1 years. All patients received radiotherapy alone using craniospinal radiotherapy and local boost. There were 10 patients (all male) with a median follow up of 10.9 years (range 2.2-18.9 years). At date of last follow up all patients were still alive, none with relapsed disease. Seven of ten patients (70%) had panhypopituitarianism prior to commencing radiotherapy and hormonal function was not affected in those with an intact pituitary axis. There was no reported cognitive decline in the treated cohort. For adult intracranial germinomas, with long term follow up, low-dose craniospinal radiotherapy with in field boost is highly effective with minimal morbidity.

Short communication: Fat-soluble vitamin and mineral status of milk replacer-fed dairy calves: effect of growth rate during the preruminant period.

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 D(3), and zinc were unaffected by growth rate. The HG calves had lower RRR-alpha-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.

Evolutionary and preservational constraints on origins of biologic groups: divergence times of eutherian mammals.

Some molecular clock estimates of divergence times of taxonomic groups undergoing evolutionary radiation are much older than the groups' first observed fossil record. Mathematical models of branching evolution are used to estimate the maximal rate of fossil preservation consistent with a postulated missing history, given the sum of species durations implied by early origins under a range of species origination and extinction rates. The plausibility of postulated divergence times depends on origination, extinction, and preservation rates estimated from the fossil record. For eutherian mammals, this approach suggests that it is unlikely that many modern orders arose much earlier than their oldest fossil records.

Effects of chronic environmental cold on growth, health, and select metabolic and immunologic responses of preruminant calves.

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 degrees 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 degrees 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-alpha, 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.

Development and prospective in-patient proof-of-concept validation of a surface photogrammetry + CT-based volumetric motion model for lung radiotherapy.

PURPOSE: We develop and validate a motion model that uses real-time surface photogrammetry acquired concurrently with four-dimensional computed tomography (4DCT) to estimate respiration-induced changes within the entire irradiated volume, over arbitrarily many respiratory cycles. METHODS: A research, couch-mounted, VisionRT (VRT) system was used to acquire optical surface data (15 Hz, ROI = 15 × 20 cm2 ) from the thoraco-abdominal surface of a consented lung SBRT patient, concurrently with their standard-of-care 4DCT. The end-exhalation phase from the 4DCT was regarded as reference and for each remaining phase, deformation vector fields (DVFs) with respect to the reference phase were computed. To reduce dimensionality, the first two principal components (PCs) of the matrix of nine DVFs were calculated. In parallel, ten phase-averaged VRT surfaces were created. Surface DVFs and corresponding PCs were computed. A principal least squares regression was used to relate the PCs of surface DVF to those of volume DVFs, establishing a relationship between time-varying surface and the underlying time-varying volume. Proof-of-concept validation was performed during each treatment fraction by concurrently acquiring 30 s time series of real-time surface data and "ground truth" kV fluoroscopic data (FL). A ray-tracing algorithm was used to create a digitally reconstructed fluorograph (DRF), and motion trajectories of high-contrast, soft-tissue, anatomical features in the DRF were compared with those from kV FL. RESULTS: For five of the six fluoroscopic acquisition sessions, the model out-performed 4DCT in predicting contour Dice coefficient with respect to fluoroscopy-derived contours. Similarly, the model exhibited a marked improvement over 4DCT for patch positions on the diaphragm. Model patch position errors varied from 5 to -15 mm while 4DCT errors ranged between 5 and -22.4 mm. For one fluoroscopic acquisition, a marked change in the a priori internal-external correlation resulted in model errors comparable to those of 4DCT. CONCLUSIONS: We described the development and a proof-of-concept validation for a volumetric motion model that uses surface photogrammetry to correlate the time-varying thoraco-abdominal surface to the time-varying internal thoraco-abdominal volume. These early results indicate that the proposed approach can result in a marked improvement over 4DCT. While limited by the duration of the fluoroscopic acquisitions as well as the resolution of the acquired images, the DRF-based proof-of-concept technique developed here is model-agnostic, and therefore, has the potential to be used as an in-patient validation tool for other volumetric motion models.

Radiological Kinetics of Brain Metastases and Clinical Implications for Patients Treated With Stereotactic Radiosurgery.

AIMS: Select patients with brain metastases receive stereotactic radiosurgery (SRS) with the objective of improving survival and intracranial disease control. Brain metastases number and volume are prognostic factors used to inform patient selection. The aim of this study was to assess the rate of change of brain metastases size and number (growth kinetics) between the diagnostic and day of SRS magnetic resonance imaging (MRI) scans. MATERIALS AND METHODS: All patients treated with Gamma Knife SRS between October 2015 and April 2017 were included in this single-centre retrospective analysis. Brain metastases number and diameter were recorded at diagnosis and treatment. For patients with multiple brain metastases, the largest lesion was the index lesion. Distant intracranial control and overall survival were reported from the date of SRS. RESULTS: In total, 146 patients received 156 episodes of SRS. The median interval between diagnostic and SRS MRI was 20 days (range 1-68). Interval growth in the index lesion of at least 3 mm or the development of a new brain metastasis was noted in 60.2% of patients. This was associated with age less than 60 years (P = 0.001), Eastern Cooperative Oncology Group (ECOG) performance status 2 or above (P = 0.04), non-small cell lung carcinoma (NSCLC) (P = 0.03) or melanoma histologies (P = 0.05) and uncontrolled extracranial disease (P = 0.05). These patients were also more likely to develop distant intracranial recurrence (P = 0.046). Clinically significant growth was not associated with scan interval or differences in overall survival. The Kaplan-Meier estimate of probability of survival at 12 months was 59.3% (95% confidence interval 46.7-75.2%) for all patients. CONCLUSION: Intracranial progression between diagnosis and day of SRS is common. Risk factors are uncontrolled extracranial disease, poorer performance status, NSCLC or melanoma histologies and age less than 60 years. These patients would benefit from an MRI closer to treatment to inform patient selection and target delineation for SRS planning.

Vacuum and forceps training in residency: experience and self-reported competency.

OBJECTIVE: Determine chief residents' experience with vacuum and forceps deliveries and self-perceived competencies with the procedures. STUDY DESIGN: Study 1: A written questionnaire was mailed to all fourth year residents in US RRC approved Ob/Gyn programs. Study 2: The study was replicated using a web-based survey the following year. Data were analyzed with chi (2) and Wilcoxon Signed Rank tests using SPSS. RESULTS: Surveys were received from 238 residents (20%) in Study 1 and 269 residents in Study 2 (23%, representing 50% of all residency programs). In both studies, residents reported performing significantly less forceps than vacuum deliveries. Virtually all residents wanted to learn to perform both deliveries, indicated attendings were willing to teach both, and felt competent to perform vacuum deliveries (Study 1, 94.5%; Study 2, 98.5%); only half felt competent to perform forceps deliveries (Study 1, 57.6%; Study 2, 55.0%). The majority of residents who felt competent to perform forceps deliveries reported that they would predominately use forceps or both methods of deliveries in their practice (Study 1, 75.8%; Study 2, 64.6%). The majority of residents who reported that they did not feel competent to perform forceps deliveries reported that they would predominately use vacuum deliveries in their practice (Study 1, 86.1%; Study 2, 84.2%). CONCLUSION: Current training results in a substantial portion of residents graduating who do not feel competent to perform forceps deliveries. Perceived competency affected future operative delivery plans.

High growth rate fails to enhance adaptive immune responses of neonatal calves and is associated with reduced lymphocyte viability.

The objective of the study was to evaluate the effects of 3 targeted growth rates on adaptive (i.e., antigen-specific) immune responses of preruminant, milk replacer-fed calves. Calves (9.1 +/- 2.4 d of age) were assigned randomly to one of 3 dietary treatments to achieve 3 targeted daily rates of gain [no growth (maintenance) = 0.0 kg/d, low growth = 0.55 kg/d, or high growth = 1.2 kg/d] over an 8-wk period. The NRC Nutrient Requirements of Dairy Cattle calf model computer program was used to estimate the milk replacer intakes needed to achieve target growth rates. All calves were fed a 30% crude protein, 20% fat, all-milk protein milk replacer reconstituted to 14% dry matter. Diets were formulated to ensure that protein would not be limiting. All calves were vaccinated 3 wk after initiation of dietary treatments with Mycobacterium bovis, strain bacillus Calmette-Guerin and ovalbumin. Growth rates for no-growth (0.11 kg/d), low-growth (0.58 kg/d), and high-growth (1.16 kg/d) calves differed throughout the experimental period. Blood glucose concentrations in high-growth calves increased with time and were higher than in low- and no-growth calves. Mononuclear and polymorphonuclear leukocyte percentages in peripheral blood were unaffected by growth rate but did change with advancing age. Percentages of CD4(+) T cells increased with age in no-growth and low-growth calves, a characteristic of maturation, but failed to increase in high-growth calves. Growth rate did not affect the percentages of CD45RO(+) (memory) CD4(+) and CD8(+) T cells, antigen (i.e., ovalbumin)-specific serum IgG concentrations, or antigen (i.e., purified protein derivative)-induced IFN-gamma and nitric oxide secretion by mononuclear cell cultures. Antigen-elicited cutaneous delayed-type hypersensitivity responses of no-growth calves exceeded responses of low-growth, but not high-growth, calves. In resting- and antigen-stimulated cell cultures, viabilities of CD4(+), CD8(+), and gammadeltaTCR(+) T cells from high-growth calves were lower than those of the same T cell subsets from no-growth and low-growth calves. Alternatively, resting cultures of mononuclear leukocytes from high-growth calves produced more nitric oxide than those from no-growth and low-growth calves. In conclusion, adaptive immune responses were affected minimally by growth rate. The results suggest that protein-energy malnutrition in the absence of weight loss is not detrimental to antigen-specific responses of neonatal vaccinated calves and that a high growth rate does not enhance these responses. The negative effect of a high growth rate on the viability of circulating T cell populations may influence infectious disease resistance of the calf.