A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). MATERIAL AND METHODS: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). RESULTS: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). CONCLUSION: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients

Aims To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. Methods Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. Results The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13–3.63) and 1.84 (1.26–2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good–excellent result for 86% of patients (AU)

Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients.

AIMS: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. METHODS: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. RESULTS: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13-3.63) and 1.84 (1.26-2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good-excellent result for 86% of patients. CONCLUSIONS: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reported no toxicity after 6 months and good-excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

Radiation-induced acute dysphagia : Prospective observational study on 42 head and neck cancer patients.

PURPOSE: Acute toxicity in head and neck (H&N) cancer patients treated with definitive radiotherapy (RT) has a crucial role in compliance to treatments. The aim of this study was to correlate doses to swallowing-associated structures and acute dysphagia. METHODS: We prospectively analyzed 42 H&N cancer patients treated with RT. Dysphagia (grade ≥ 3) and indication for percutaneous endoscopic gastrostomy (PEG) insertion were classified as acute toxicity. Ten swallowing-related structures were considered for the dosimetric analysis. The correlation between clinical information and the dose absorbed by the contoured structures was analyzed. Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for normal tissue complication probability (NTCP) modelling. RESULTS: A strong multiple correlation between dosimetric parameters was found. A two-variable model was suggested as the optimal order by bootstrap method. The optimal model (Rs = 0.452, p < 0.001) includes V45 of the cervical esophagus (odds ratio [OR] = 1.016) and Dmean of the cricopharyngeal muscle (OR = 1.057). The model area under the curve was 0.82 (95% confidence interval 0.69-0.95). CONCLUSION: Our results suggested that the absorbed dose to the cricopharyngeal muscle and cervical esophagus might play a relevant role in the development of acute RT-related dysphagia.

VERO® radiotherapy for low burden cancer: 789 patients with 957 lesions.

PURPOSE: The aim of this retrospective study is to evaluate patient profile, feasibility, and acute toxicity of RadioTherapy (RT) delivered by VERO® in the first 20 months of clinical activity. METHODS: Inclusion criteria: 1) adult patients; 2) limited volume cancer (M0 or oligometastatic); 3) small extracranial lesions; 4) treatment between April 2012 and December 2013 and 5) written informed consent. Two techniques were employed: intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT). Toxicity was evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) criteria. RESULTS: Between April 2012 and December 2013, 789 consecutive patients (957 lesions) were treated. In 84% of them one lesion was treated and in 16% more than one lesion were treated synchronously/metachronously; first radiotherapy course in 85%, re-irradiation in 13%, and boost in 2% of cases. The treated region included pelvis 46%, thorax 38%, upper abdomen 15%, and neck 1%. Radiotherapy schedules included <5 and >5 fractions in 75% and 25% respectively. All patients completed the planned treatment and an acceptable acute toxicity was observed. CONCLUSIONS: RT delivered by VERO® was administrated predominantly to thoracic and pelvic lesions (lung and urologic tumours) using hypofractionation. It is a feasible approach for limited burden cancer offering short and well accepted treatment with favourable acute toxicity profile. Further investigation including dose escalation and other available VERO® functionalities such as real-time dynamic tumour tracking is warranted in order to fully evaluate this innovative radiotherapy system.

Salvage image-guided intensity modulated or stereotactic body reirradiation of local recurrence of prostate cancer.

OBJECTIVE: To retrospectively evaluate external beam reirradiation (re-EBRT) delivered to the prostate/prostatic bed for local recurrence, after radical or adjuvant/salvage radiotherapy (RT). METHODS: 32 patients received re-EBRT between February 2008 and October 2013. All patients had clinical/radiological local relapse in the prostate or prostatic bed and no distant metastasis. re-EBRT was delivered with selective RT technologies [stereotactic RT including CyberKnife(TM) (Accuray, Sunnyvale, CA); image-guidance and intensity-modulated RT etc.]. Toxicity was evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Biochemical control was assessed according to the Phoenix definition (NADIR + 2 ng ml(-1)). RESULTS: Acute urinary toxicity: G0, 24 patients; G1, 6 patients; G2, 2 patients. Acute rectal toxicity: G0, 28 patients; G1, 2 patients; and G2, 1 patient. Late urinary toxicity (evaluated in 30 cases): G0, 23 patients; G1, 6 patients; G2, 1 patient. Late renal toxicity: G0, 25 patients; G1, 5 patients. A mean follow-up of 21.3 months after re-EBRT showed that 13 patients were free of cancer, 3 were alive with biochemical relapse and 12 patients were alive with clinically evident disease. Four patients had died: two of disease progression and two of other causes. CONCLUSION: re-EBRT using modern technology is a feasible approach for local prostate cancer recurrence offering 2-year tumour control in about half of the patients. Toxicity of re-EBRT is low. Future studies are needed to identify the patients who would benefit most from this treatment. ADVANCES IN KNOWLEDGE: Our series, based on experience in one hospital alone, shows that re-EBRT for local relapse of prostate cancer is feasible and offers a 2-year cure in about half of the patients.

Contrast-enhanced ultrasound findings in soft-tissue lesions: preliminary results.

OBJECTIVES: There is currently no widely available, minimally invasive first-level examination that allows physicians to identify soft-tissue lesions that are likely to be malignant. The aim of this pilot study was to explore the potential suitability of dynamic contrast-enhanced ultrasound (DCE-US) for this purpose. MATERIALS AND METHODS: 23 patients were referred to the Veneto Oncological Institute for work-up of superficial soft-tissue lesions. Fourteen lesions were examined with CEUS and enhancement kinetics was analyzed. Subsequently, all lesions were surgically removed and subjected to histological analysis. RESULTS: The 14 lesions included in the study were histologically classified as malignant (n = 7) or benign (n = 7, including 3 schwannomas). A statistically significant difference between benign and malignant lesions was found in terms of mean times to peak enhancement intensity (p = 0.03) but not mean filling times (FT). When schwannomas were analyzed as a separate group, their mean FT was found to be significantly different from that of the other benign lesions (p = 0.001) and from that of the group comprising other benign lesions as well as malignant lesions (p < 0.005). CONCLUSIONS: CEUS with analysis of contrast-enhancement kinetics is a relatively low-cost, minimally invasive imaging technique, which appears to be a potentially effective first-level method for identifying suspicious soft-tissue masses.

Experimental evaluation of birds as disseminators of the cosmopolitan tick Rhipicephalus sanguineus (Acari: Ixodidae).

Rhipicephalus sanguineus is believed to be the most widespread tick species of the world and its dissemination seems to rely on the diffusion of its main host, the dog. Empirical observations indicate that several bird species in urban areas regularly steal dog food. Such circumstances create a chance for R. sanguineus ticks to climb on birds and carry ticks to another site. In this work we evaluated experimentally the likelihood of birds (chicks) to either feed and/or carry R. sanguineus ticks from an infested site to another and to infest a host (rabbit) in the new location. Chicks were not suitable hosts for R. sanguineus ticks. Not a single adult tick engorged on chicks, yield as well as weight of engorged larvae and nymphs were very low and feeding period of these ticks was very long. However, a few larvae and, chiefly, nymphs were delivered to a new location either mechanically or after attachment and engorging total or partially on chicks. A few of these ticks fed successfully on rabbits. Further evidence on the capacity of birds to introduce R. sanguineus into non-infested dog settings should be provided by systematic examination of birds from urban areas, close to tick infested households.

Role of psychotherapy in the management of psychiatric diseases.

Psychotherapy plays an essential role in the treatment of mental disorders. The use and research of psychological treatment strategies increased drastically over the past decade. The general efficacy of psychotherapy for the treatment of psychiatric diseases is proved and documented in several meta-analyses. Psychotherapy re-searchers have found solutions for acceptable study designs which account for the special character of these interventions and studied the efficacy of psychotherapeutic treatment in more than 1000 intervention trials.Meanwhile evidence-based psychotherapy approaches tailored to a specific diagnosis are dominating the field and question the basis of psychotherapy schools.A new field of research in psychotherapy is the neurobiological basis of mental disorders and the demonstration of neurobiological changes with psycho-therapeutic treatment.

Life cycle of the tick Amblyomma parvum Aragão, 1908 (Acari: Ixodidae) and suitability of domestic hosts under laboratory conditions.

Amblyomma parvum is a widespread Neotropical tick found on several domestic animals and is known to harbor a Rickettsia species of yet unknown pathogenicity. However its life cycle on, and suitability of, several of these hosts has not been described. In this work the biology of A. parvum is presented when fed on seven domestic hosts (chicken, dog, rabbit, horse, guinea pig, cattle and goat). The complete life cycle of the tick varied from 96.8 to 102 days. Highest engorgement weight of larvae was from ticks fed on horses and that of nymphs from guinea pigs. Highest larval yield was from guinea pigs and that of nymphs from horses. Engorged female and egg mass weights, yield and conversion of female weight to eggs rates were the highest in dog ticks and the lowest in goat ticks. The highest egg hatching rate was seen in ticks from dogs and the lowest in ticks from cattle. Overall it was seen that dogs were the best host for adult A. parvum ticks, and guinea pigs for immatures. Horses were also shown to be a good host for all tick stages. It can thus be affirmed that A. parvum is a host generalist tick, and its distribution is probably determined by environmental requirements rather than by hosts.

Impedance vector distribution by body mass index and conventional bioelectrical impedance analysis in obese women.

BACKGROUND AND AIM: To compare the body fluid status assessments provided by conventional bioelectrical impedance analysis (BIA) and vector BIA in moderate and severe obesity. METHODS AND RESULTS: We studied 516 normotensive Caucasian women (mean age: 48 +/- 9.2 years), who were age-matched and divided into four groups on the basis of their body mass index (BMI): 99 normal weight women with a BMI of 19-25 Kg/m2; 228 preobese overweight women with a BMI of 25-30 Kg/m2; 132 women with class I-II obesity (BMI: 30-35 Kg/m2), and 57 women with class III obesity (BMI: 40-64 Kg/m2). Single-frequency (50 kHz) tetrapolar (hand-foot) bioelectrical impedance measurements were made, and total body water (TBW) and extracellular water (ECW) were estimated using conventional BIA regression equations. The RXc graph method was used for vector BIA, with the set of 327 women with a BMI of 19-30 Kg/m2 being adopted as the reference population. Mean vector displacement followed a definite pattern, with progressive vector shortening as the BMI increased, and along a fixed phase angle. This pattern indicates more TBW due to a greater soft tissue mass with average normal hydration. Short and downsloping vectors indicating fluid overload were more frequent in the group with class III obesity than in the group with class I obesity (19 vs 5%). The absolute values of TBW and ECW were significantly higher in the obese and overweight subjects than in those with normal weight subjects. TBW as a percentage of body weight was significantly lower in the obese subjects. CONCLUSIONS: BMI influenced the impedance vector distribution pattern, which proved to be consistent up to a BMI of 64 Kg/m2. Obese women with an altered body composition can be identified and monitored using vector BIA.

Plasma leptin measurements in epidemiological investigation: comparison of two commonly used assays and estimate of regression dilution bias.

BACKGROUND AND AIM: As leptin is the object of intensive clinical research, we compared the radio-immunological assay (RIA) and enzyme-linked immunosorbent assay (ELISA) commercially available for measuring its plasma concentration in humans (Study 1), and sought to determine the power of a single plasma leptin measurement to characterise adequately a subject within a population on the basis of its intra- and inter-individual variations (Study 2). METHODS AND RESULTS: Study 1--Plasma leptin concentrations were determined by means of RIA and ELISA in a sample of 80 males. The measurements obtained using the two methods were closely correlated (r = 0.942), but the bias of the means was 21.1 +/- 73.5% (M +/- SD, p < 0.001) and indicated that the two assays were not in agreement with each other. As expected, there were strong statistical associations between plasma leptin and a number of anthropometric indices, but the slopes of the regression of leptin concentration was significantly steeper when measured by ELISA. Study 2--ELISA was used to measure plasma leptin concentrations in three different samples obtained from 12 males and 12 females at two-week intervals. The inter-individual variation in plasma leptin was much greater than its intra-individual variation (the ratio of intra-to inter-individual variance = 0.05 and 0.04 in males and females, respectively), thus suggesting that a single fasting measurement is sufficient to characterise an individual's plasma leptin level within a population. CONCLUSIONS: ELISA is at least as effective as RIA in measuring plasma leptin, and is fully suitable for epidemiological investigations. A single measurement made in the morning and under fasting conditions is sufficient to characterise an individual within a population.

Injury prevention and control in children.

Injury is the number one cause of death and life-years lost for children. In children, injury mortality is greater than childhood mortality from all other causes combined. Modern injury prevention and control seeks to prevent and limit or control injuries through the 4 Es of injury prevention: engineering, enforcement, education, and economics. Emergency physicians are often placed in a critical role in the lives of individuals, are respected authorities on the health and safety of children and adults, and have daily exposure to high-risk populations. This gives emergency physicians a unique perspective and an opportunity to take an active role in injury control and prevention. Specific methods or strategies for promulgating injury prevention and control in our emergency medicine practices are suggested, ranging from education (for our patients and health professionals); screening and intervention for domestic violence, child maltreatment, drug-alcohol dependency and abuse; data collection; reporting unsafe products; research; legislation; serving in regulatory and governmental agencies; emergency medical services-community involvement; and violence prevention. Emergency physicians can play a significant role in decreasing pediatric injury and its concomitant morbidity and mortality.

The potential for errors in children with special health care needs.

Children with special health care needs (CSHCN) are at risk for suboptimal treatment when presenting for emergent care to unfamiliar health care providers. Errors in their management may stem from failure to recognize occult conditions, lack of familiarity with rare or complex medical problems, or lack of prior knowledge of baseline physical findings. An emergency information form (EIF) that contains patient-specific information on essential diagnostic and therapeutic interventions may provide a ready personal reference for the emergent care of CSHCN. Coupled with the use of medical identification jewelry and an electronic transmission system, an EIF has the potential to eliminate management errors in the care of these patients.

International Guidelines for Neonatal Resuscitation: An excerpt from the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Contributors and Reviewers for the Neonatal Resuscitation Guidelines.

The International Guidelines 2000 Conference on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiac Care (ECC) formulated new evidenced-based recommendations for neonatal resuscitation. These guidelines comprehensively update the last recommendations, published in 1992 after the Fifth National Conference on CPR and ECC. As a result of the evidence evaluation process, significant changes occurred in the recommended management routines for: * Meconium-stained amniotic fluid: If the newly born infant has absent or depressed respirations, heart rate <100 beats per minute (bpm), or poor muscle tone, direct tracheal suctioning should be performed to remove meconium from the airway. * Preventing heat loss: Hyperthermia should be avoided. * Oxygenation and ventilation: 100% oxygen is recommended for assisted ventilation; however, if supplemental oxygen is unavailable, positive-pressure ventilation should be initiated with room air. The laryngeal mask airway may serve as an effective alternative for establishing an airway if bag-mask ventilation is ineffective or attempts at intubation have failed. Exhaled CO(2) detection can be useful in the secondary confirmation of endotracheal intubation. * Chest compressions: Compressions should be administered if the heart rate is absent or remains <60 bpm despite adequate assisted ventilation for 30 seconds. The 2-thumb, encircling-hands method of chest compression is preferred, with a depth of compression one third the anterior-posterior diameter of the chest and sufficient to generate a palpable pulse. * Medications, volume expansion, and vascular access: Epinephrine in a dose of 0.01-0.03 mg/kg (0.1-0.3 mL/kg of 1:10,000 solution) should be administered if the heart rate remains <60 bpm after a minimum of 30 seconds of adequate ventilation and chest compressions. Emergency volume expansion may be accomplished with an isotonic crystalloid solution or O-negative red blood cells; albumin-containing solutions are no longer the fluid of choice for initial volume expansion. Intraosseous access can serve as an alternative route for medications/volume expansion if umbilical or other direct venous access is not readily available. * Noninitiation and discontinuation of resuscitation: There are circumstances (relating to gestational age, birth weight, known underlying condition, lack of response to interventions) in which noninitiation or discontinuation of resuscitation in the delivery room may be appropriate.

The role of emergency physicians in the care of the child in school.

Emergency physicians may contribute significantly to the health of children in the school setting. Because children spend the majority of their waking hours in school, they and their adult caretakers experience medical and surgical emergencies on a regular basis. These emergencies include a wide range of problems, such as asthma, seizures, firearms violence, and mass disasters. Additionally, many children in school have limited access to primary care, which increases their risk for medical emergencies. Recent reports from the National Academy of Sciences Institute of Medicine and the Maternal and Child Health Bureau's Emergency Medical Services for Children Program have described the challenges in improving the medical care of children in both the emergency and school settings. The prevalence of school health emergencies provides an opportunity for use of the expertise of emergency physicians. Emergency physicians have an important role in ensuring the proper treatment of emergency medical problems that occur in school. They need to be integrally involved in the development and organization of systems for prevention, initial stabilization, definitive management, and responsible follow-up of medical problems and injuries.

Boomerang babies: emergency department utilization by early discharge neonates.

INTRODUCTION: Since 1987 the average length of stay for infants following hospital delivery has decreased 1.8 days. This study was undertaken to evaluate the null hypothesis that early discharge of newborns from nurseries does not result in increased emergency department (ED) utilization during the first 10 days of life. SITE: Thirty community EDs, one university ED. METHODS: Retrospective review of ED visits of patients two to 10 days of age from 1989 to 1995. The absolute number of ED neonatal visits (NVs) was compared to the total number of ED visits for each year and the ratio of NV/10,000 ED visits determined. The disposition and diagnosis of each patient was noted, and the number and percent of infants admitted to the hospital calculated. RESULTS: A total of 3.1 million ED visits were reviewed, and 2094 NVs identified. The ratio of NV/10,000 ED visits increased from 4.3 in 1989 to 7.8 in 1995 (P < 0.001), while the average length of stay for deliveries decreased from 2.79 days to 1.85 days. The mean percent of patients admitted from the ED was 10.3% and showed no statistically significant changes over the study period. The majority of visits were for minor medical or educational problems. CONCLUSION: The null hypothesis is rejected. Early discharge of neonates does result in increased ED utilization. No increase in admission rates for these infants was documented, indicating that patient severity did not increase with ED utilization. There is a need for improved predischarge education and greater access for episodic ambulatory complaints.