Optimized workflow to minimise intra-fractional motion during stereotactic body radiotherapy of spinal metastases.

Background and purpose: This study evaluated translational and rotational intra-fractional patient movement during spinal stereotactic body radiotherapy (SBRT) using 6D positioning based on 3D cone beam computerized tomography (CBCT) and stereoscopic kilovoltage imaging (ExacTrac). The aim was to determine whether additional intra-fractional image verification reduced intra-fractional motion without significantly prolonging treatment time, whilst maintaining acceptable imaging related dose. Materials and methods: A retrospective analysis of 38 patients with 41 primary tumour volumes treated with SBRT between September 2018 and May 2021 was performed. Three different image-guided radiotherapy (IGRT) workflows were assessed. The translational and rotational positioning errors for the different imaging workflows, 3D translational vectors and estimates of imaging dose delivered for the different imaging workflows were evaluated. Results: As the frequency of intra-fractional imaging increased from workflow 1 to 3, the mean intra-fraction 3D translational vector improved from 0.91 mm (±0.52 mm), to 0.64 (±0.34 mm). 85 %, 83 % and 97 % of images were within a tolerance of 1 mm/1° for workflows 1, 2 and 3 respectively, based on post treatment CBCT images. The average treatment time for workflow 3 was 13 min, as compared to 12 min for workflows 1 and 2. The effective dose per treatment for IGRT workflows 1, 2 and 3 measured 0.6 mSv, 0.95 mSv and 1.8 mSv respectively. Conclusion: The study demonstrated that the use of additional intra-fractional stereoscopic kilovoltage image-guidance during spinal SBRT, reduced the number of measurements deemed "out of tolerance" and treatment delivery could be optimized within a standard treatment timeslot without applying substantial additional radiation dose.

The addition of deep hyperthermia to gemcitabine-based chemoradiation may achieve enhanced survival in unresectable locally advanced adenocarcinoma of the pancreas.

INTRODUCTION: Driven by the current unsatisfactory outcomes for patients with locally advanced pancreatic cancer (LAPC), a biologically intensified clinical protocol was developed to explore the feasibility and efficacy of FOLFORINOX chemotherapy followed by deep hyperthermia concomitant with chemoradiation and subsequent FOLFORINOX chemotherapy in patients with LAPC. METHODS: Nine patients with LAPC were treated according to the HEATPAC Phase II trial protocol which consists of 4 cycles of FOLFORINOX chemotherapy followed by gemcitabine-based chemoradiation to 56 Gy combined with weekly deep hyperthermia and then a further 8 cycles of FOLFORINOX chemotherapy. RESULTS: One grade three related toxicity was reported and two tumours became resectable. The median overall survival was 24 months and 1 year overall survival was 100%. CONCLUSIONS: Intensification of chemoradiation with deep hyperthermia was feasible in nine consecutive patients with LAPC.

Enhancing Low-Intensity Coaching in Parent Implemented Early Start Denver Model Intervention for Early Autism: A Randomized Comparison Treatment Trial.

Short-term low intensity parent implemented intervention studies for toddlers with autism spectrum disorder (ASD) have found it difficult to demonstrate significantly improved developmental scores or autism severity compared to community treatment. We conducted a randomized comparative intent-to-treat study of a parent implemented intervention to (1) test the effects of an enhanced version on parent and child learning, and (2) evaluate the sensitivity to change of proximal versus distal measures of child behavior. We randomized 45 children with ASD, 12-30 months of age, into one of two versions of parent-implemented Early Start Denver Model (P-ESDM), the basic model, in which we delivered 1.5 h of clinic-based parent coaching weekly, and an enhanced version that contained three additions: motivational interviewing, multimodal learning tools, and a weekly 1.5-h home visit. We delivered the intervention for 12 weeks and measured child and parent change frequently in multiple settings. We found a time-by-group interaction: parents in the enhanced group demonstrated significantly greater gains in interaction skills than did parents in the non-enhanced group. Both interventions were associated with significant developmental acceleration; however, child outcomes did not differ by group. We found a significant relationship between degree of change in parental interaction skill and rate of children's improvement on our proximal measure. Parents in both groups reported satisfaction with the intervention. These findings suggest that parent skills improved more in the enhanced group than the comparison group. Children in the two groups showed similar improvements. Rate of individual parent learning was associated with greater individual child progress on a measure quite proximal to the treatment, though not on standardized assessments.

Changes in vertebral bone marrow fat and bone mass after gastric bypass surgery: A pilot study.

Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6 months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean ± SD decline 19.1 ± 6.1 kg or 36.5% ± 10.9%, p<0.001). Areal bone mineral density (BMD) decreased by 5.2% ± 3.5% and 4.1% ± 2.6% at the femoral neck and total hip, respectively, and volumetric BMD decreased at the spine by 7.4% ± 2.8% (p<0.001 for all). Effects of RYGB on marrow fat differed by diabetes status (adjusted p=0.04). There was little mean change in marrow fat in nondiabetic women (mean +0.9%, 95% CI -10.0 to +11.7%, p=0.84). In contrast, marrow fat decreased in diabetic women (-7.5%, 95% CI -15.2 to +0.1%, p=0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r=-0.96, p=0.01) but not diabetic (r=0.52, p=0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots.

Autism treatment in the first year of life: a pilot study of infant start, a parent-implemented intervention for symptomatic infants.

The goal of early autism screening is earlier treatment. We pilot-tested a 12-week, low-intensity treatment with seven symptomatic infants ages 7-15 months. Parents mastered the intervention and maintained skills after treatment ended. Four comparison groups were matched from a study of infant siblings. The treated group of infants was significantly more symptomatic than most of the comparison groups at 9 months of age but was significantly less symptomatic than the two most affected groups between 18 and 36 months. At 36 months, the treated group had much lower rates of both ASD and DQs under 70 than a similarly symptomatic group who did not enroll in the treatment study. It appears feasible to identify and enroll symptomatic infants in parent-implemented intervention before 12 months, and the pilot study outcomes are promising, but testing the treatment's efficacy awaits a randomized trial.

Layered stigma among health-care and social service providers toward key affected populations in Jamaica and The Bahamas.

While considerable research has documented stigma toward key populations affected by HIV and AIDS - men who have sex with men (MSM), sex workers (SWs) - it provided limited empirical evidence on the presence of layered stigma among health-care professionals providing services for these populations. C-Change conducted a survey among 332 staff of health-care and social service agencies in Jamaica and The Bahamas to understand the levels of stigma toward people living with HIV (PLHIV), including MSM and SWs and factors associated with stigma. While most health-care professionals responding to the survey said that PLHIV, MSM, and SWs deserved quality care, they expressed high levels of blame and negative judgments, especially toward MSM and SWs. Across a stigma assessment involving eight vignette characters, the highest levels of stigma were expressed toward PLHIV who were also MSM or SWs, followed by PLHIV, MSM, and SWs. Differences were assessed by gender, country, type of staff, type of agency, and exposure to relevant training. Findings indicate higher reported stigma among nonclinical vs. clinical staff, staff who worked in general vs. MSM/SW-friendly health facilities, and among untrained vs. training staff. This implies the need for targeted staff capacity strengthening as well as improved facility environments that are MSM/SW-friendly.

Bariatric surgery in a patient with complete MC4R deficiency.

Bariatric surgery is often successful for treatment of severe obesity. The mechanisms of weight loss after bariatric surgery and the role of central energy homeostatic pathways in this weight loss process are not well understood. The study of individuals with complete loss of function of genes important in the leptin-melanocortin system may help establish the significance of these pathways for weight loss after bariatric surgery. We describe the outcome of bariatric surgery in an adolescent with compound heterozygosity and complete functional loss of both alleles of the melanocortin 4 receptor (MC4R). The patient underwent laparoscopic adjustable gastric banding and truncal vagotomy at years of age, which resulted in initial, but not long-term weight loss. Our experience with this patient suggests that complete MC4R deficiency impairs response to gastric banding and results in poor weight loss after this surgery.

Routine upper GI series after gastric bypass does not reliably identify anastomotic leaks or predict stricture formation.

BACKGROUND: Many surgeons who perform Roux-en-Y gastric bypass (RYGB) for morbid obesity routinely obtain an upper gastrointestinal (GI) series in the early postoperative period to search for anastomotic leaks and signs of stricture formation at the gastrojejunostomy. We hypothesized that this practice is unreliable. METHODS: We analyzed 654 consecutive RYGBs, of which 63% were completed laparoscopically. An upper GI series was obtained in 634 (97%) patients. The radiographic findings (leak or delayed emptying) were compared with clinical outcomes (leak or stricture formation) to calculate the sensitivity and specificity. Univariate analysis identified risk factors for leaks or stricture formation; events were too few for multivariate analysis. RESULTS: Of 634 routine upper GI series, anastomotic leaks at the gastrojejunostomy were diagnosed in 5 (0.8%); 2 of these 5 were later reinterpreted as artifacts. Four leaks were not seen on the initial upper GI series, yielding an overall sensitivity of 43% and a positive predictive value (PPV) of 60%. Univariate analysis showed that cases done early (odds ratio [OR] 5.4 for the first 100 cases, p = 0.02) and prolonged operating time (OR 7.8 for cases >or= 300 min, p = 0.01) were associated with leaks. Emptying into the Roux-en-Y limb was delayed in 127 (20%) of the upper GI series. Strictures requiring dilatation developed in 16 (2.4%) patients. The PPV of delayed emptying for stricture formation was 6%. Risk factors for stricture formation included stapled anastomosis (OR 7.8, p = 0.002), surgeon inexperience (OR 2.9 for first 50 cases, p = 0.04), and delayed emptying (OR 3.3; p = 0.02). CONCLUSIONS: Because the incidence of anastomotic complications and the sensitivity of upper GI series were both low, routine upper GI series did not reliably identify leaks or predict stricture formation. A selective approach, whereby imaging is reserved for patients with clinical evidence of a leak or stricture, may be more appropriate.

A preliminary study of screening for risk of autism in children with fragile X syndrome: testing two risk cut-offs for the Checklist for Autism in Toddlers.

OBJECTIVE: Risk criteria for the Checklist for Autism in Toddlers (CHAT) and modified risk criteria (i.e. the Denver Criteria) were compared in a group of children with fragile X syndrome (FXS) and autism. METHOD: Participants were 17 children aged 2-4 years with DNA confirmation of FXS. Four children had autism and 13 children did not. RESULTS: Preliminary findings regarding the sensitivity and specificity of the CHAT for detecting risk for autism in children with FXS are as follows: using the original CHAT risk criteria, sensitivity and specificity were 50% and 100%, respectively; and using the Denver Criteria, sensitivity and specificity were 75% and 92%, respectively. CONCLUSIONS: The CHAT and the Denver Criteria resulted in preliminary findings suggesting high levels of sensitivity to autism in children with FXS.

Emotional responsivity in children with autism, children with other developmental disabilities, and children with typical development.

Twenty six children with autism, 24 children with developmental disabilities, and 15 typically developing children participated in tasks in which an adult displayed emotions. Child focus of attention, change in facial tone (i.e., hedonic tone), and latency to changes in tone were measured and summary scores of emotional contagion were created. Group differences existed in the ratio of episodes that resulted in emotional contagion. Correlations existed between measures of emotional contagion, measures of joint attention, and indices of severity of autism. Children with autism demonstrated muted changes in affect, but these responses occurred much less frequently than in comparison groups. The findings suggest directions for early identification and early treatment of autism.

Gefitinib (ZD1839, Iressa) as palliative treatment in recurrent or metastatic head and neck cancer.

To assess the level of activity and toxicity of gefitinib (ZD1839, Iressatrade mark) in a population of patients with locally recurrent and/or metastatic head and neck cancer. Patients were recruited into an expanded access programme through the multidisciplinary head and neck clinics at the Royal Marsden and St George's Hospitals. Patients were required to have received at least one course of standard systemic chemotherapy or radiation therapy, or be medically unfit for chemotherapy. Patients were commenced on single-agent gefitinib at a dose of 500 mg day(-1). Clinical, symptomatic and radiological response, time to progression (TTP), survival and toxicity were recorded. A total of 47 patients were enrolled (35 male and 12 female) with a median age of 62 years (range 18-93 years). The observed clinical response rate was 8% with a disease control rate (complete response, partial response, stable disease) of 36%. In all, 34% of patients experienced an improvement in their symptoms. The median TTP and survival were 2.6 and 4.3 months, respectively. Acneiform folliculitis was the most frequent toxicity observed (76%) but the majority of cases were grade 1 or 2. Only four patients experienced grade 3 toxicity of any type (all cases of folliculitis). Gefitinib was well tolerated and yielded symptomatic improvement in one-third of patients. However, this agent appeared to possess limited antitumour activity in this group of patients with head and neck cancer in whom the objective response rate, median TTP and survival were all lower than has been reported in a previous study.

Radiotherapy of localised intracranial germinoma: time to sever historical ties?

The optimum management of localised intracranial germinoma remains controversial. Cure rates for this rare CNS tumour, which arises mainly in adolescents, exceed 90% at 10 years, and limitation of treatment-related late morbidity is therefore essential. Craniospinal radiotherapy plus boost is perceived to be the gold-standard treatment, but there have been suggestions that reduced-volume radiotherapy could be adequate for cure. We reviewed publications since 1988 to compare patterns of disease relapse and cure rates after craniospinal radiotherapy, reduced-volume irradiation alone (i.e., whole-brain or whole-ventricular irradiation followed by a boost), and focal or localised irradiation alone. The recurrence rate after whole-brain or whole-ventricular radiotherapy plus boost was 7.6% compared with 3.8% after craniospinal radiotherapy, with no predilection for isolated spinal relapses (2.9% vs 1.2%). We challenge the consensus that craniospinal radiotherapy is the best treatment for localised germinomas and conclude that reduced-volume radiotherapy plus boost should replace craniospinal radiotherapy when a radiotherapy-only approach is used.

Auditory evoked magnetic fields in adults with fragile X syndrome.

Hyper-reactivity and anxiety to sensory stimuli have been described in patients with fragile X syndrome (FXS), and may be related to abnormal processing in afferent sensory pathways. We used magnetoencephalography (MEG) to measure auditory responses to pure tones in 11 adults with FXS and 11 non-FXS subjects. The amplitude for the N100m auditory evoked field component was significantly higher for patients with FXS than for subjects. FXS subjects also had less lateralized N100m anterior-posterior dipole locations. These data may suggest that more neurons are activated by acoustic stimuli in FXS, consistent with subjective experience of increased stimulus intensity. Anomalous cerebral lateralization may suggest an early critical window for effects on neocortical development of the fragile X mental retardation protein (FMRP) produced by the FMR1 gene in individuals with FXS.

Equal care ensures equal survival for African-American women with cervical carcinoma.

BACKGROUND: [corrected] It was the purpose of this study to investigate whether race is an independent prognostic factor in the survival of patients with cervical carcinoma in a health care system with minimal racial bias, and few barriers to access to care. METHODS: Records for patients with a diagnosis of invasive cervical carcinoma from 1988 to 1999 were obtained from the Automated Central Tumor Registry for the United States Military Health Care System. Clinical data including race, age at diagnosis, histology, grade, stage, socioeconomic status, treatment modality, and survival also were obtained. Survival analysis was performed with Kaplan-Meier survival curves. RESULTS: One thousand five hundred fifty-three patients were obtained for review. Sixty-five percent of patients were Caucasian, and 35% were minorities. Of the minorities, 29% were African Americans (AAs). Mean age of diagnosis was similar among AAs and Caucasians, 44 and 42 years, respectively. There was no statistically significant difference between the distribution of age, stage, grade, or histology between Caucasians and AAs. Forty-six percent of patients were treated with surgery and 56% with radiation therapy, with no difference in type of treatment between the Caucasian and AA groups. Five- and 10-year survival rates for Caucasians and AAs were 75%, and 76%, and 64% 65% (P = 0.59), respectively. CONCLUSIONS: In an equal access, unbiased, nonracial environment, race is not an independent predictor of survival for patients with cervical carcinoma. This study has shown, for the first time to the authors' knowledge, that when they receive equal treatment for cervical carcinoma, AA women's survival can approach that of their nonminority counterparts (75% at 10 years).

Understanding of others' intentions in children with autism.

Many studies have shown that children with autism have difficulty understanding the thoughts and beliefs of other people. However, little research has been conducted on what these children understand about simpler mental states such as intentions. The current study tested the understanding of others' intentions in 2 1/2- to 5-year-old children with autism and a control group of children with other developmental delays. We used Meltzoff's (1995) test of understanding of others' unfulfilled intentions in an imitation context, with an additional "End State" condition. We found no significant between-group differences on any measure involving the understanding of others' intentions. Although within-group patterns suggested that children with autism may have a slightly less complex understanding of others' intentions than do other children, it was clear that any deficits these children showed in this area were not as marked as those they typically show on traditional theory of mind tasks.

Can the checklist for autism in toddlers differentiate young children with autism from those with developmental delays?

OBJECTIVE: The Checklist for Autism in Toddlers (CHAT) has been demonstrated to be sensitive to the presence of autism in otherwise normally developing 18-month-old children. However, its ability to differentiate autism from other significant developmental delays is unknown. This study examined this question. METHOD: The CHAT was applied to a group of 44 children aged 2 and 3 years, rigorously diagnosed with autism or with other developmental problems. RESULTS: By the original CHAT authors' criteria, the sensitivity and specificity of the CHAT were 65% and 100%, respectively. Slightly altering the criteria resulted in a sensitivity of 85% in the current group of children with developmental disabilities while maintaining specificity of 100%. CONCLUSIONS: The current study is the first to demonstrate that the CHAT successfully discriminates 2-year-old children with autism from those with other developmental disorders. In addition, the increased sensitivity of the Denver Criteria in children with developmental disabilities may improve its usefulness as a screening tool for community-based early-diagnostic teams and general practitioners.

Predictors of treatment outcome in young children with autism: a retrospective study.

This study examined predictors of developmental outcomes in 17 children diagnosed with autism or PDD-NOS, who received generic treatment over a mean period of 37 months. Pre-treatment evaluations occurred at a mean age of 31 months with follow-up evaluations at a mean age of 69 months. Significantly different developmental trajectories were observed among the participants at follow-up, separating the participants into two distinct groups (high and low outcome). However, groups did not differ significantly in treatment intensity or other outcome prediction measures. Pre-treatment developmental intelligence levels between the two groups approached significance. The results raise questions regarding the effect of treatment intensity and type, family stress factors, and intelligence ability in very early childhood on, outcome.

The behavioral phenotype in fragile X: symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders.

This study was designed to explore the behavioral phenotype of autism in a group of young children with fragile X syndrome (FXS). Twenty-four children with FXS, ages 21 to 48 months, were compared with two well-matched groups: 27 children with autism (AD) and 23 children with other developmental delays (DD), on two standardized autism instruments, as well as on measures of development and adaptive behavior. Two FXS subgroups emerged. One subgroup (n = 16) did not meet study criteria for autism. Their profiles on the autism instruments and the developmental instruments were virtually identical to the other DD group. The other FXS subgroup (n = 8, or 33% of the total FXS group) met study criteria for autism. Their profiles on the autism instruments were virtually identical to the group with autism. The finding of two FXS subgroups raises a hypothesis of additional genetic influences in the FXS autism group, warranting further genetic studies.

Interventions that facilitate socialization in children with autism.

Social dysfunction is perhaps the most defining and handicapping feature of autism. Improved social functioning has long been considered one of the most important intervention outcomes. A variety of social interventions have been designed, empirically examined, and published in the autism literature. Children with autism have been found to be responsive to a wide variety of interventions aimed at increasing their social engagement with others, both adults and peers. Successful strategies employing peer-mediated approaches and peer tutoring have involved typically developing peers. Furthermore, several studies have demonstrated that social engagement directly affects other important behaviors like language, even when these behaviors are not specifically targeted by the teaching program. Thus, while an area of severe involvement, social behavior is also responsive to intervention.

Use of CT Hounsfield unit density to identify ablated tumor after laparoscopic radiofrequency ablation of hepatic tumors.

BACKGROUND: When attempting to interpret CT scans after radiofrequency thermal ablation (RFA) of liver tumors, it is sometimes difficult to distinguish ablated from viable tumor tissue. Identification of the two types of tissue is specially problematic for lesions that are hypodense before ablation. The aim of this study was to determine whether quantitative Hounsfield unit (HU) density measurements can be used to document the lack of tumor perfusion and thereby identify ablated tissue. METHODS: Liver spiral CT scans of 13 patients with 51 lesions undergoing laparoscopic RFA for metastatic liver tumors within a 2-year time period were reviewed. HU density of the lesions as well as normal liver were measured pre- and postoperatively in each CT phase (noncontrast, arterial, portovenous). Statistical analyses were performed using Student's paired t-test and ANOVA. RESULTS: Normal liver parenchyma, which was used as a control, showed a similar increase with contrast injection in both pre- and postprocedure CT scans (56.4 +/- 2.4 vs 57.1 +/- 2.4 HU, respectively; p = 0.3). In contrast, ablated liver lesions showed a preablation increase of 45.7 +/- 3.4 HU but only a minimal postablation increase of 6.6 +/- 0.7 HU (p < 0.0001). This was true for highly vascular tumors (neuroendocrine) as well as hypovascular ones (adenocarcinoma). CONCLUSIONS: This is the first study to define quantitative radiological criteria using HU density for the evaluation of ablated tissues. A lack of increase in HU density with contrast injection indicates necrotic tissue, whereas perfused tissue shows an increase in HU density. This technique can be used in the evaluation of patients undergoing RFA.