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Biomarkers for oligometastatic disease remain elusive and few studies have attempted to correlate genomic data to the presence of true oligometastatic disease. Patients with non-small cell lung cancer (NSCLC) and brain metastases were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based comprehensive genomic profiling (Guardant Health) was available. Oligometastatic disease was defined as patients having ≤5 non-brain metastases without diffuse involvement of a single organ. Widespread disease was any spread beyond oligometastatic. Fisher's exact tests were used to identify mutations statistically associated (p<0.1) with either oligometastatic or widespread extracranial disease. A score of +1 was assigned for every mutation present associated with oligometastatic disease, and -1 was assigned for mutations associated with widespread disease. Scores were summed for each patient to create a risk score for the likelihood of oligometastatic disease, with scores subsequently correlated to the likelihood of having oligometastatic disease vs widespread disease. For oligometastatic patients, a competing risk analysis was done to assess for cumulative incidence of oligometastatic progression accounting for the potential competing risks of widespread progression of extracranial disease or death. Cox regression was used to determine the association between oligometastatic risk score and oligometastatic progression. One hundred thirty patients met study criteria and were included in the analysis. 51 patients (39%) had oligometastatic disease. Genetic mutations included in the Guardant panel associated (p<0.1) with the presence of oligometastatic extracranial disease included ATM, JAK2, MAP2K2, and NTRK1; ARID1A and CCNE1 were associated with widespread disease. Patients with a positive, neutral and negative risk score for oligometastatic disease had a 78%, 41% and 11.5% likelihood of having oligometastatic disease, respectively (p<0.0001). Overall survival for patients with positive, neutral and negative risk scores for oligometastatic disease was 86% vs 82% vs 64% at 6 months (p = 0.2). The competing risk analysis found that the oligometastatic risk score was significantly associated with the likelihood of oligometastatic progression based on the Wald Chi-square test. Patients with positive, neutral and negative risk scores for oligometastatic disease had a cumulative incidence of oligometastatic progression of 77% vs 35% vs 33% at 6 months (p = 0.03 from competing risk model). Elucidation of a genomic signature for oligometastatic disease derived from non-invasive liquid biopsy appears feasible for NSCLC patients. Patients with the oligometastatic signature exhibited higher rates of early oligometastatic progression. Validation of this signature could lead to a biomarker that has the potential to direct local therapies in oligometastatic patients. [ABSTRACT FROM AUTHOR]

Unilateral neck radiotherapy (RT) is standard for patients with well-lateralized T1-2 tonsil carcinoma with limited neck disease (N0 or single node <3 cm). For patients that do not fit these criteria, particularly those with more advanced neck disease, unilateral neck RT is controversial. The reduction in toxicity associated with unilateral RT must be balanced with the risk of contralateral neck failure (CNF). Due to a paucity of data regarding this risk, the ideal candidates for ipsilateral neck irradiation remain to be elucidated. A systemic review of PubMed, Embase, and Web of Science was performed (PROSPERO ID #CRD42021237637). Publications between January 1980 to June 2021 were included for analysis if they contained >20 patients treated with ipsilateral definitive of post-operative radiation for tonsil cancer. Primary outcome was the pooled crude rate of CNF. Secondary outcomes included pooled rates of CNF stratified by T/N stage and xerostomia and gastrostomy tube use. Random effect models were used to estimate the risk of CNF and exploratory meta-regression was employed. In 4 studies that reported both ipsilateral and bilateral RT, meta-analytic log odd ratios were used to compare risk of CNF. A total of 17 studies (16 retrospective, 1 prospective) consisting of 1,487 patients were identified. Overall, the pooled crude risk of CNF was 1.9% (95% CI 1.2-2.6). The rate of CNF by T-stage was as follows: T1 (n=458), 1.3% (0.3-2.3); T2 (n=537), 3.0% (1.6-4.4); T3 (n=54), 11.3% (3.3-19.2); T4 (n=8), 16.0% (0.0-39.8). Patients with T3-T4 tumors had a significantly higher rate of CNF than those with T1-T2 tumors: 11.6% (95% CI 4.0-19.3%) and 1.8% (1.0-2.6%), respectively (p<0.001). The rate of CNF by N stage was: N0 (n=474), 1.2% (95% CI 0.1-2.2); N1 (n=295), 4.8% (2.4-7.2); N2a (n=146), 3.11% (0.04- 5.8); N2b (n=339), 3.1% (1.2-4.9); N3 (n=32), 0% (N/A). Rates of CNF were similar for patients with N2b-N3 and N0-N2a disease: 3% (95% CI 1.2-4.7%) and 1.7% (0.6-2.8%), respectively (p=0.072). Compared to bilateral RT, ipsilateral RT was associated with increased risk of CNF (log odds ratio 1.286 [95% CI 0.086-2.485], p=0.036). Exploratory meta-regression analyses suggest an association between CNF and chemotherapy, HPV, surgical management, and smoking. In terms of toxicity, the crude rates of grade 3 xerostomia (n=304) and feeding tube use (n=588) were 0.9% (95% CI 0-1.9%) and 13.3% (8.3-18.3), respectively. Ipsilateral neck irradiation is associated with a higher risk of CNF compared to bilateral irradiation, though the overall rate of CNF is low. Patients with higher T-stage are at increased risk for CNF following ipsilateral neck irradiation. These findings are among the strongest available evidence to support ipsilateral RT in T1-2N0-2b lateralized tonsil cancer and may facilitate informed risk-benefit discussions with patients. [ABSTRACT FROM AUTHOR]

Type-2 diabetes mellitus is associated with a 2- to 4-fold increase in the risk of clinical coronary artery disease (CAD). It has been suggested that diabetic subjects without clinical CAD should be treated as aggressively for cardiovascular risk factors as subjects with CAD. This would be warranted if diabetic subjects without clinical CAD would have accelerated CAD similar to that of nondiabetic subjects with symptomatic CAD. To assess this suggestion, we compared the intima-media wall thickness in the common carotid artery (CCA) and internal carotid artery (ICA) in 43 diabetic subjects with clinical CAD, 446 diabetic subjects without clinical CAD, 47 nondiabetic subjects with clinical CAD, and 975 nondiabetic subjects without clinical CAD (all aged 40 to 70 years) in the Insulin Resistance Atherosclerosis Study. All data were adjusted for age, gender, ethnicity, and clinical results. Both diabetes and CAD were associated with increased atherosclerosis in the CCA. Likewise, diabetes was significantly associated with increased atherosclerosis in the ICA; however, CAD was not associated with ICA intima-media wall thickness. As expected, diabetic subjects with CAD had the greatest intima-media wall thickness, whereas nondiabetic subjects without CAD had the least atherosclerosis. Subjects with diabetes but without CAD had slightly greater intima-media wall thickness than nondiabetic subjects with CAD, although these differences were not statistically significant. Thus, diabetic subjects even without CAD had extensive atherosclerosis in the carotid artery. These results support the suggestion that diabetic subjects should be treated as aggressively for cardiovascular risk factor management as subjects with pre-existing CAD. [ABSTRACT FROM AUTHOR]

Biomarkers for leptomeningeal disease (LD) are not well elucidated in the literature. Few studies have shown a correlation between genomic data and LD. Patients with brain metastases were identified in our departmental database. The electronic medical record was used to identify patients with liquid-biopsy-based comprehensive genomic profiling (Guardant Health). LD was defined as patients with clinical, cytologic (lumbar puncture) or radiographic evidence of LD. LD risk scores were developed based on the number of genetic mutations they have that are associated with time to LD. Cox proportional hazards regression analyses were used to assess the association between mutations and progression to LD. Hazard ratios were calculated to quantify the risk of developing LD in those with specific genetic mutations compared to those without. A score of +1 was assigned for every mutation present associated with LD with a threshold of p<0.1 to be entered into the model. Patients were then placed into one of three risk groups (0 genes present, 1 gene present, 2+genes present). Product limit survival estimates were developed to provide information on the probability of survival without LD. Two-hundred and four patients met study criteria and were included in the analysis. Twelve gene mutations were associated (p<0.1) with developing LD (APC (p = 0.014), ARID1A (p=0.04), CDH1 (p=0.09), DDR2 (p=0.04), EGFR (p = 0.06), MPL (p=0.017), MSH2 (p=0.016), NTRK3 (p = 0.005), PMS2 (p = 0.036) PTPN11 (p=0.09), RAF1 (p=0.033)and SMO (p = 0.021). When risk groups were constructed, 102 patients had none of the twelve genes present, 82 patients had one of the twelve genes present, and 20 patients had at least 2 genes present. We found that 4/102 (3.9%) of the patients with 0 genes, 10/82 (12.2%) with 1 gene, and 10/20 (50%) with 2 or more genes developed LD (Chi Square-34.2, p<0.0001). The Cox proportional hazards regression model indicated that the 3-level genetic risk score was highly associated with time to LD (Wald Chi-Square=18.8, p<0.0001). This model also showed that patients with 2+ genes had a hazard ratio (HR) for time to LD of 12.7 (p<0.0001) when compared to patients with 0 genes, and patients with 1 gene had a HR of 4.6 (p=0.01) for time to LD when compared to patients with 0 genes. Using the product limit survival analysis model, we determined the 6-month, 1- and 2-year cumulative incidence of LD estimates were 0%, 3%, and 3% for patients with no genes present, 2%, 4%, and 18% for patients with one gene present and 11%, 11%, and 18% for patients with 2 or more genes present, respectively. Genomic profiling appears to provide a meaningful LD risk score from non-invasive liquid biopsies. Those with higher risk scores were more likely to have LD in their lifetime with certain mutations predisposing a patient at an earlier time point. Validation of this signature could lead to a biomarker with the potential to influence clinical trial enrollment and surveillance mechanisms in this population. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study fast voluntary neck movements in patients with cervical dystonia (CD) before and after therapy with botulinum toxin type-A (BTX-A). Methods: A selected sample of 15 patients with CD (with prevalent torticollis) and 13 age-matched control subjects performed both right and left rotational, and flexion and extension neck movements as fast as possible. Movements were recorded with a motion analysis system (SMART, BTS). Movement time, angular amplitude, and peak angular velocity were analyzed. In patients, rotational neck movements were pooled as “pro-dystonic” (toward the dystonic side) and “anti-dystonic” (toward the non-dystonic side). Results obtained in patients before BTX-A treatment were compared with those of control subjects. The effect of BTX-A treatment was evaluated by comparing movement performance before and after treatment. Results: Before receiving BTX-A, patients performed pro- and anti-dystonic movements with lower peak angular velocity than control subjects. Pro-dystonic movements had a reduced angular amplitude. Anti-dystonic movements showed an abnormally long movement time. Flexion and extension movements required longer movement times, but the other kinematic variables were normal. After BTX-A injections, pro-dystonic movement amplitude and anti-dystonic movement peak angular velocity increased, whereas flexion and extension movements remained unchanged. Conclusions: Before BTX-A injection patients with CD perform fast voluntary neck movements abnormally and BTX-A injections improved their peak velocity and amplitude. Significance: Kinematic studies can detect specific neck movement disturbance in patients with CD, and can quantify both the severity of clinical picture and the effect of BTX-A injections in these patients. [Copyright &y& Elsevier]

In this study we tested the antimicrobial activity of polyethylene films modified by means of plasma processes that were followed by the chemical immobilization of lysozyme, an antimicrobial enzyme. To chemically immobilize the enzyme in its active form at the surface of polyethylene, substrates that had been plasma treated under different experimental conditions were soaked in lysozyme solutions at different concentrations. The immobilization of the enzyme was checked, and the antimicrobial activity of the films was investigated by observing the death rate of Micrococcus lysodeikticus cells suspended in phosphate buffer in contact with the films. The results clearly indicate that plasma-treated films loaded with lysozyme are active against the selected microorganism. A modified version of the Gompertz equation was used to quantitatively valuate the dependence of the antimicrobial activity of the films under both plasma treatment conditions and lysozyme concentrations. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To find out whether parkinsonian patients with levodopa-induced peak-dose dyskinesias are bradykinetic. Methods: The performance of a sequential internally determined arm movement and a simple externally triggered arm movement was studied in a group of dyskinetic parkinsonian patients during their best clinical condition and when they were OFF treatment. Patients'' performance was compared with that of an age-matched control group. Movements in the three-dimensional space were recorded by the ELITE motion analysis system. Kinematic variables analysed for the sequential motor task were total movement duration and total pause duration; for the simple motor task, movement duration and reaction time; and for both tasks, movement inaccuracy. Results: When patients were OFF therapy they performed sequential and simple movement tasks slower than healthy subjects whereas when they were dyskinetic they did not. During the sequential task, when the patients were dyskinetic total pause duration shortened and movement inaccuracy increased. Conclusions: Our kinematic finding indicates that parkinsonian patients'' with peak-dose dyskinesias are not bradykinetic. Significance: Parkinsonian patients with peak-dose dyskinesias are not bradykinetic, probably because dopamine at peak doses functionally normalizes the mechanisms controlling movement speed. [Copyright &y& Elsevier]

Adenoidectomy is one of the most frequent operations in children. In order to reduce hospital stay costs, today, this procedure is performed as day surgery. Even though adenoidectomy is not considered risky, some minor complications may occur, the most important being bleeding (0.5–8% incidence). The surgical technique used can influence considerably postoperative pain and time to recovery. This aspect is essential in the management of day surgery patients, for whom the need of safe and rapid manoeuvers associated with early recovery determines the choice of the surgical procedure.Recently, we developed a surgical technique based on the use of an electronic molecular resonance tool associated with bendable suction electrocautery.This study was carried out on 600 patients, divided into two groups, the first undergoing ablation using the molecular resonance tool and the second undergoing curette adenoidectomy. The two groups were homogeneous for age, sex, surgical indications, and grade of adenoid hypertrophy. The following parameters were considered: duration of surgery, importance of intraoperative bleeding, time to cicatrization, incidence of bleeding complications.Duration of surgery and intra- and postoperative bleeding were much lower in the first group than in the group undergoing traditional adenoidectomy. In addition, rhinopharyngeal complete cicatrization, defined as absolute absence of pseudomembrane, was much quicker in the first group, as assessed by postoperative endoscopy.Another major advantage offered by the molecular resonance tool is the accuracy of surgery performed under visual control in a practically bloodless field.To sum up, this method, thanks to its technical features and safety, is particularly indicated in children and in patients with coagulation disorders. [Copyright &y& Elsevier]

This retrospective study reviews our experience in the management of acute otomastoiditis over 10 years. During the study period we identified 40 cases in children aged 3 months–15 years with a peak incidence in the second year of life. Sixty per cent of them had a history of acute otitis media (AOM). All the children were already receiving oral antibiotic therapy. Otalgia, fever, poor feeding and vomiting were the most common symptoms, all the children had evidence of retroauricolar inflammation. Computerized tomography (CT) and magnetic resonance imaging (MRI) were used to support the diagnosis and to evaluate possible complications. Streptococcus pneumoniae was the most common isolated bacterium. All the patients received intravenous antibiotics, 65% of children received only medical treatment, 35% also underwent surgical intervention. Mean length of hospital stay was 12.3 days. Cholesteathoma was diagnosed in one child. We conclude from our study that acute otomastoiditis is a disease mainly affecting young children, that develops from AOM resistant to oral antibiotics. Adequate initial management always requires intravenous antibiotics, conservative surgical treatment with miryngotomy is appropriate in children not responding within 48 h from beginning of therapy. Mastoidectomy should be performed in all the patients with acute coalescent mastoiditis or in case of evidence of intracranial complications. [Copyright &y& Elsevier]

No prior studies have attempted to identify a biomarker for initial brain metastasis velocity (iBMV), with limited studies attempting to correlate genomic data to the development of brain metastases. Patients with non-small cell lung cancer (NSCLC) were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based next-generation sequencing (NGS) was available. The presence of brain metastasis (BM) was determined through review of magnetic resonance imaging of the brain, both at time of diagnosis and during follow-up. iBMV was calculated by dividing the number of BM by the interval of time between primary cancer and BM diagnosis. An iBMV of 300 was assigned to patients with BM at time of primary diagnosis and a score of 0 to patients who never developed BM during a minimum follow-up of 2 years. 2 sample t-testing was used to identify mutations statistically associated (P <0.1) with iBMV. A value of +1 was assigned to each mutation with a positive association with increased iBMV ("deleterious genes"), and a value of -1 to each mutation present with an inverse association ("protective genes"). The sum of these values was calculated to define iBMV risk scores, which ranged in values from -1 to +3. iBMV risk scores of +1, +2 and +3 were pooled into a single group and assigned a score of +1. A survival analysis model that allowed for competing risks was fit to examine the time to development of BM allowing for death as a competing risk. 312 patients met study criteria and were included in the analysis. 218 (70%) developed brain metastases. Genetic mutations in the NGS panel that were found to be associated with elevated iBMV ("deleterious genes") included ARID1A, BRAF, CDK4, GNAQ, MLH1, MSH6, PALB2, RAD51D, RB1 and TSC1; those with an inverse association to iBMV ("protective genes") included ARAF, IDH1, MYC, and PTPN11. Patients with a positive (n = 95), neutral (n = 197) and negative (n = 20) iBMV risk score, had an 88%, 61% and 65% likelihood of developing BM, respectively (P <0.0001). A competing risk analysis found a statistically significant association between iBMV risk scores of 1 vs 0 and 1 vs -1, respectively, and the likelihood of developing BM using death as a competing risk (HR = 2.35, 95% CI = 1.77-3.11 and HR = 2.57, 95% CI = 1.57-4.20). Overall survival for patients with positive, neutral and negative iBMV risk scores was 72% vs 84% vs 85% and 46% vs 69% vs 70% at 1- and 2-years, respectively (P <0.023). Development of a genomic signature for iBMV via non-invasive liquid biopsy appears feasible in NSCLC patients. Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules. [ABSTRACT FROM AUTHOR]

We recently presented a genomic signature that was predictive of both oligometastatic disease state and oligometastatic progression in patients with brain metastases. We sought to validate this oligometastatic genomic signature using an independent dataset of patients without brain metastases. Patients with non-small cell lung cancer (NSCLC) and without brain metastases were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based comprehensive genomic profiling (Guardant Health) was available. Oligometastatic disease was defined as patients having ≤5 extracranial metastases without diffuse involvement of a single organ. Patients were given a risk score for oligometastatic disease based on the previously derived genomic signature consisting of genes associated with oligometastatic disease (ATM, JAK2, MAP2K2, and NTRK1) and with widespread disease (ARID1A and CCNE1). Scores were summed for each patient to create a risk score for the likelihood of oligometastatic disease, with scores subsequently correlated to the likelihood of having oligometastatic disease vs widespread disease. For oligometastatic patients, a competing risk analysis was then performed to assess the cumulative incidence of oligometastatic progression accounting for the potential competing risks of widespread progression of extracranial disease or death. Cox regression was used to determine association between oligometastatic risk score and oligometastatic progression. 225 patients met study criteria and were included in the validation dataset. 158 patients (70%) had oligometastatic disease. Patients with positive and neutral/negative risk scores for oligometastatic disease had a 70% vs 48% likelihood of having oligometastatic disease, respectively (P = 0.03 from Fisher's exact test), demonstrating that the genomic profile was again statistically significantly associated with the likelihood of oligometastatic disease on our validation dataset. Patients with positive risk scores for oligometastatic disease more frequently experienced oligometastatic progression with a hazard ratio of 1.72 (P = 0.11 from competing risk model). Overall survival for patients with positive and neutral/negative risk scores for oligometastatic disease was 92% vs 79% at 6 months; 46% vs 60% at 12 months; 23% vs 34% at 24 months (P = 0.25). The results of the validation dataset are consistent with our previously reported genomic profile for oligometastatic disease in patients with brain metastases. In this larger, independent dataset, our genomic signature predicted oligometastatic disease state and showed a trend towards prediction of oligoprogression. With further study, our findings may suggest a biomarker with future potential to direct local therapies in oligometastatic patients with NSCLC. [ABSTRACT FROM AUTHOR]