Postoperative IMRT in head and neck cancer

BACKGROUND: Aim of this work was to assess loco-regional disease control in head and neck cancer (HNC) patients treated with postoperative intensity modulated radiation therapy (pIMRT). For comparative purposes, risk features of our series have been analysed with respect to histopathologic adverse factors. Results were compared with an own historic conventional radiation (3DCRT) series, and with 3DCRT and pIMRT data from other centres. Between January 2002 and August 2006, 71 patients were consecutively treated with pIMRT for a squamous cell carcinoma (SCC) of the oropharynx (32), oral cavity (22), hypopharynx (7), larynx (6), paranasal sinus (3), and an unknown primary, respectively. Mean and median follow up was 19 months (2–48), and 17.6 months. 83% were treated with IMRT-chemotherapy. Mean prescribed dose was 66.3 Gy (60–70), delivered with doses per fraction of 2–2.3 Gy, respectively. RESULTS: 2-year local, nodal, and distant control rates were 95%, 91%, and 96%, disease free and overall survival 90% and 83%, respectively. The corresponding survival rates for the subgroup of patients with a follow up time >12 months (n = 43) were 98%, 95%, 98%, 93%, and 88%, respectively. Distribution according to histopathologic risk features revealed 15% and 85% patients with intermediate and high risk, respectively. All loco-regional events occurred in the high risk subgroup. CONCLUSION: Surgery followed by postoperative IMRT in patients with substantial risk for recurrence resulted in high loco-regional tumor control rates compared with large prospective 3DCRT trials

Explaining variability in early stages of [18F]-flortaucipir tau-PET binding: Focus on sex differences

INTRODUCTION Female sex is associated with increased [18F]-flortaucipir signal, which may be affected by amyloid pathology, age, and off-target binding in skull and meninges. METHODS In this cross-sectional study comprising 52 females and 52 matched males, we examined sex-related differences in regional tau-positron emission tomography (PET) with and without considering off-target binding. We assessed the respective contributions of sex, age, amyloid-PET burden, and off-target binding to tau-PET signal. We explored associations between age at menopause and hormone replacement therapy (HRT) use with regional tau-PET signals. RESULTS Female sex was associated with increased regional tau both independently and interactively with amyloid, but amyloid-independent associations were largely reduced when controlling for off-target binding. Age but not age*sex interactions explained a small but significant amount of tau-PET signal in temporoparietal regions. Considering the sample size and limited range of amyloid-PET burden, no clear associations between regional tau-PET signals and age at menopause or HRT use could be found. DISCUSSION Female sex is associated with increased [18F]-flortaucipir signal mainly through its interaction with amyloid

Lifestyle Affects Amyloid Burden and Cognition Differently in Men and Women

OBJECTIVE Evidence on associations of lifestyle factors with Alzheimer's pathology and cognition are ambiguous, potentially because they rarely addressed inter-relationships of factors and sex effects. While considering these aspects, we examined the relationships of lifestyle factors with brain amyloid burden and cognition. METHODS We studied 178 cognitively normal individuals (women, 49%; 65.0 [7.6] years) and 54 individuals with mild cognitive impairment (women, 35%; 71.3 [8.3] years) enrolled in a prospective study of volunteers who completed $^{18}$ F-Flutemetamol amyloid positron emission tomography. Using structural equation modeling, we examined associations between latent constructs representing metabolic/vascular risk, physical activity, and cognitive activity with global amyloid burden and cognitive performance. Furthermore, we investigated the influence of sex in this model. RESULTS Overall, higher cognitive activity was associated with better cognitive performance and higher physical activity was associated with lower amyloid burden. The latter association was weakened to a nonsignificant level after excluding multivariate outliers. Examination of the moderating effect of sex in the model revealed an inverse association of metabolic/vascular risk with cognition in men, whereas in women metabolic/vascular risk trended toward increased amyloid burden. Furthermore, a significant inverse association between physical activity and amyloid burden was found only in men. Inheritance of an APOE4 allele was associated with higher amyloid burden only in women. INTERPRETATION Sex modifies effects of certain lifestyle-related factors on amyloid burden and cognition. Notably, our results suggest that the negative impact of metabolic/vascular risk influences the risk of cognitive decline and Alzheimer's disease through distinct paths in women and men. ANN NEUROL 2022;92:451-463

Down regulation of E-Cadherin (ECAD) - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx

<p>Abstract</p> <p>Background</p> <p>Prognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC) are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections.</p> <p>Objectives</p> <p>To determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease.</p> <p>Methods</p> <p>E-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue), 10 tumours in the oropharynx (8.3%). Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS). These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance.</p> <p>Results</p> <p>pT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (<it>p </it>= 0.018) and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (<it>p </it>= 0.005) in univariate and multivariate analysis.</p> <p>Conclusion</p> <p>These data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx.</p> <p><b>Level of evidence: 2b</b></p

There is no evidence that carbon dioxide-enriched oxygen before apnea affects the time to arterial desaturation, but it might improve cerebral oxygenation in anesthetized obese patients: a single-blinded randomized crossover trial

Purpose Carbon dioxide (CO$_{2}$) increases cerebral perfusion. The effect of CO$_{2}$ on apnea tolerance, such as after anesthesia induction, is unknown. This study aimed to assess if cerebral apnea tolerance can be improved in obese patients under general anesthesia when comparing O$_{2}$/Air (95%O$_{2}$) to O$_{2}$/CO$_{2}$ (95%O$_{2}$/5%CO$_{2}$). Methods In this single-center, single-blinded, randomized crossover trial, 30 patients 18–65 years, with body mass index > 35 kg/m$^{2}$, requiring general anesthesia for bariatric surgery, underwent two apneas that were preceded by ventilation with either O$_{2}$/Air or O$_{2}$/CO$_{2}$ in random order. After anesthesia induction, intubation, and ventilation with O$_{2}$/Air or O$_{2}$/CO$_{2}$ for 10 min, apnea was performed until the cerebral tissue oxygenation index (TOI) dropped by a relative 20% from baseline (primary endpoint) or oxygen saturation (SpO$_{2}$) reached 80% (safety abortion criterion). The intervention was then repeated with the second substance. Results The safety criterion was reached in all patients before cerebral TOI decreased by 20%. The time until SpO$_{2}$ dropped to 80% was similar in the two groups (+ 6 s with O$_{2}$/CO$_{2}$, 95%CI -7 to 19 s, p = 0.37). Cerebral TOI and PaO$_{2}$ were higher after O$_{2}$/CO$_{2}$ (+ 1.5%; 95%CI: from 0.3 to 2.6; p = 0.02 and + 0.6 kPa; 95%CI: 0.1 to 1.1; p = 0.02). Conclusion O$_{2}$/CO$_{2}$ improves cerebral TOI and PaO$_{2}$ in anesthetized bariatric patients. Better apnea tolerance could not be confirmed

Are bear-dogs morphologically similar to bears and/or dogs? A preliminary morphological analysis of their cranial system during the Cenozoic.

peer reviewe

Functional Brain Network Connectivity Patterns Associated With Normal Cognition at Old-Age, Local β-amyloid, Tau, and APOE4

Background: Integrity of functional brain networks is closely associated with maintained cognitive performance at old age. Consistently, both carrier status of Apolipoprotein E ε4 allele (APOE4), and age-related aggregation of Alzheimer's disease (AD) pathology result in altered brain network connectivity. The posterior cingulate and precuneus (PCP) is a node of particular interest due to its role in crucial memory processes. Moreover, the PCP is subject to the early aggregation of AD pathology. The current study aimed at characterizing brain network properties associated with unimpaired cognition in old aged adults. To determine the effects of age-related brain change and genetic risk for AD, pathological proteins β-amyloid and tau were measured by Positron-emission tomography (PET), PCP connectivity as a proxy of cognitive network integrity, and genetic risk by APOE4 carrier status. Methods: Fifty-seven cognitively unimpaired old-aged adults (MMSE = 29.20 ± 1.11; 73 ± 8.32 years) were administered 11C Pittsburgh Compound B and 18F Flutemetamol PET for assessing β-amyloid, and 18F AV-1451 PET for tau. Individual functional connectivity seed maps of the PCP were obtained by resting-state multiband BOLD functional MRI at 3-Tesla for increased temporal resolution. Voxelwise correlations between functional connectivity, β-amyloid- and tau-PET were explored by Biological Parametric Mapping (BPM). Results: Local β-amyloid was associated with increased connectivity in frontal and parietal regions of the brain. Tau was linked to increased connectivity in more spatially distributed clusters in frontal, parietal, occipital, temporal, and cerebellar regions. A positive interaction was observable for APOE4 carrier status and functional connectivity with brain regions characterized by increased local β-amyloid and tau tracer retention. Conclusions: Our data suggest an association between spatially differing connectivity systems and local β-amyloid, and tau aggregates in cognitively normal, old-aged adults, which is moderated by APOE4. Additional longitudinal studies may determine protective connectivity patterns associated with healthy aging trajectories of AD-pathology aggregation

Explaining variability in early stages of [18F]-flortaucipir tau-PET binding: Focus on sex differences

Introduction: Female sex is associated with increased [18F]-flortaucipir signal, which may be affected by amyloid pathology, age, and off-target binding in skull and meninges. Methods: In this cross-sectional study comprising 52 females and 52 matched males, we examined sex-related differences in regional tau-positron emission tomography (PET) with and without considering off-target binding. We assessed the respective contributions of sex, age, amyloid-PET burden, and off-target binding to tau-PET signal. We explored associations between age at menopause and hormone replacement therapy (HRT) use with regional tau-PET signals. Results: Female sex was associated with increased regional tau both independently and interactively with amyloid, but amyloid-independent associations were largely reduced when controlling for off-target binding. Age but not age*sex interactions explained a small but significant amount of tau-PET signal in temporoparietal regions. Considering the sample size and limited range of amyloid-PET burden, no clear associations between regional tau-PET signals and age at menopause or HRT use could be found. Discussion: Female sex is associated with increased [18F]-flortaucipir signal mainly through its interaction with amyloid.ISSN:2352-872