Deciphering the Differences in Ambident Reactivity between the Cyanate, Thiocyanate Ions, and their P- and As-Containing Analogues.

Although the cyanate and thiocyanate anions belong to the most known textbook examples of ambident nucleophiles, the electronic factors that determine their markedly differing reactivities are still unclear. The recently discovered P- and As-containing [PCX]- and [AsCX]- analogues (X: O, S, Se), whose ambident nature is practically unexplored, may serve as ideal basis for comparison to clarify these differences. This study presents comprehensive theoretical investigations on the nucleophilic behaviours of the whole set of so far known [ECX]- (E: N, P, As, X: O, S, Se) anions, aiming for a systematic understanding of the reactivity patterns and identifying the factors that govern the nucleophilic substitutions. The results indicate that the SN 2 reactions of the O-containing [ECO]- ions are thermodynamically preferred at the pnictogen centres E, while the kinetic contributions are only substantial for the N-containing [NCX]- anions. The ambident reactivities of the congeners that contain N or O significantly differ from those with P, As, S, or Se heteroatoms, in line with the inert s-orbital effect, characteristic for the heavier elements. By analysing the electronic structures and bonding patterns of the anions and relevant transition state structures, clear explanations are offered for the differing reactivities of the whole set of [ECX]- anions. To serve for synthetic investigations, possible outcomes of nucleophilic substitutions are predicted, and the target molecules are expected to be versatile and useful synthons.

The role of cholesterol metabolism in multiple sclerosis: From molecular pathophysiology to radiological and clinical disease activity.

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS leading to demyelination and axonal degeneration. An increasing body of evidence suggests that lipid metabolism is associated with adverse clinical and MRI outcomes in MS. In this review we summarize the findings of association between low-density lipoproteins (LDL), high-density lipoproteins (HDL), their apolipoproteins and oxysterols with clinical and radiological disease activity in MS. Although the causality between disease activity in MS and abnormalities in lipid metabolism has not yet been elucidated, we suggest that advances in this field of research have the potential to improve understanding of MS pathophysiology and the identification of new treatment targets and strategies.

[Magnetic resonance imaging findings in 143 epileptic cats]. / Magnetresonanztomographische Befunde bei 143 Katzen mit Epilepsie.

OBJECTIVE: Epilepsy is one of the more common chronic neurological diseases in cats in which MRI plays a key role in the diagnostic work-up. Hippocampal MRI changes are common in cats, however it is unclear whether these changes represent the reason or the consequence of the disease.The goal of the present study was the retrospective analysis of the MRI findings in a large cohort of epileptic cats. MATERIAL AND METHODS: In total, 143 cats of 3 age groups (< 1 year, 1-6 years, and > 6 years) were included in the study. MRI findings were divided into 4 categories: normal, with extrahippocampal lesions, and hippocampal signal alterations with or without contrast enhancement. The prevalence and frequency of these MRI findings in the age groups were examined using chi-quadrat test and nominal regression model. RESULTS: In approximately one half of the cats (49 %), MRI displayed normal findings. Extrahippocampal changes occurred in 18 % of the animals. Hippocampal alterations were present in 33 % of the cats. Hippocampal sclerosis was found histopathologically in all four MRI categories. CONCLUSION AND CLINICAL RELEVANCE: Brain MRI was normal in approximately 50 % of the epileptic cats. Extrahippocampal changes are expected mostly in cats older than 6 years. The etiology of the hippocampal alterations is unclear in most cases. Further investigations are needed for a better understanding of the hippocampal signal alterations.

Natalizumab Induces Changes of Cerebrospinal Fluid Measures in Multiple Sclerosis.

BACKGROUND: There is a lack of knowledge about the evolution of cerebrospinal fluid (CSF) markers in multiple sclerosis (MS) patients undergoing natalizumab treatment. AIM: We aimed to evaluate the effect of natalizumab on basic inflammatory CSF and MRI measures. METHODS: Together, 411 patients were screened for eligibility and 93 subjects with ≥2 CSF examinations ≤6 months before and ≥12 months after natalizumab initiation were recruited. The effect of natalizumab on CSF as well as clinical and paraclinical measures was analyzed using adjusted mixed models. RESULTS: Natalizumab induced a decrease in CSF leukocytes (p < 1 × 10-15), CSF protein (p = 0.00007), the albumin quotient (p = 0.007), the IgG quotient (p = 6 × 10-15), the IgM quotient (p = 0.0002), the IgG index (p = 0.0004), the IgM index (p = 0.003) and the number of CSF-restricted oligoclonal bands (OCBs) (p = 0.0005). CSF-restricted OCBs positivity dropped from 94.6% to 86% but 26 patients (28%) had an increased number of OCBs at the follow-up. The baseline to follow-up EDSS and T2-LV were stable; a decrease in the relapse rate was consistent with a decrease in the CSF inflammatory markers and previous knowledge about the effectiveness of natalizumab. The average annualized brain volume loss during the follow-up was -0.50% (IQR = -0.96, -0.16) and was predicted by the baseline IgM index (B = -0.37; p = 0.003). CONCLUSIONS: Natalizumab is associated with a reduction of basic CSF inflammatory measures supporting its strong anti-inflammatory properties. The IgM index at the baseline predicted future brain volume loss during the course of natalizumab treatment.

Isolated Cognitive Decline in Neurologically Stable Patients with Multiple Sclerosis.

(1) Background: Cognitive deterioration is an important marker of disease activity in multiple sclerosis (MS). It is vital to detect cognitive decline as soon as possible. Cognitive deterioration can take the form of isolated cognitive decline (ICD) with no other clinical signs of disease progression present. (2) Methods: We investigated 1091 MS patients from the longitudinal GQ (Grant Quantitative) study, assessing their radiological, neurological, and neuropsychological data. Additionally, the confirmatory analysis was conducted. Clinical disease activity was defined as the presence of new relapse or disability worsening. MRI activity was defined as the presence of new or enlarged T2 lesions on brain MRI. (3) Results: Overall, 6.4% of patients experienced cognitive decline and 4.0% experienced ICD without corresponding clinical activity. The vast majority of cognitively worsening patients showed concomitant progression in other neurological and radiologic measures. There were no differences in disease severity between completely stable patients and cognitively worsening patients but with normal cognition at baseline. (4) Conclusions: Only a small proportion of MS patients experience ICD over short-term follow-up. Patients with severe MS are more prone to cognitive decline; however, patients with normal cognitive performance and mild MS might benefit from the early detection of cognitive decline the most.

Hippocampal size did not differ between epileptic and non-epileptic dogs using volumetric and subjective methods.

Hippocampal changes in epilepsy may manifest as hippocampal atrophy/sclerosis. A recent human study suggests that the demonstration of hippocampal volume loss is more reliable using quantitative evaluation methods. The aim of the present study was to obtain volumetric data in both epileptic and healthy dogs, to compare hippocampal volumes in both groups, and to compare subjective and volumetric assessment. Volumetric measurements of the hippocampi, lateral ventricles and hemispheria were performed in 31 epileptic and 15 control dogs. There was a positive association between the body weight and the hemispheric volume, as well as between the hemispheric volume and the ipsilateral hippocampal volume. There was no significant correlation between age and the volume of any measured brain structures. There was no statistically significant difference between the hippocampal volumes of the control group and the epileptic group. A statistically significant difference between the two groups for hippocampus/hemispherium ratio or hippocampal asymmetric ratio was not identified. An extrapolated hippocampal volume based on body weight was not possible in this study population.

Oncological and Functional Outcomes of Transoral Robotic Surgery and Endoscopic Laryngopharyngeal Surgery for Hypopharyngeal Cancer: A Systematic Review.

Objectives: Hypopharyngeal carcinoma (HPC) is a head and neck carcinoma with poor prognosis. Traditional laryngopharyngectomy offered promising oncological outcomes at the cost of functional outcomes. The recent advent in transoral robotic surgery (TORS), an organ-preserving surgery, has opened up new perspectives in the treatment for HPC. Here, we evaluate minimally invasive organ preservation surgery [TORS and endoscopic laryngopharyngeal surgery (ELPS)] for HPC in terms of feasibility and oncological and functional outcomes. Methods: This is a systematic review. Six databases [CUHK Full-Text Journals, Embase 1910 to 2021, Ovid Emcare, Ovid MEDLINE (R), CINAHL, PubMed] were searched for articles and primary studies for TORS and ELPS for HPC. Screening was completed using predefined inclusion or exclusion criteria. Results: A total of 8 studies on TORS and 3 studies on ELPS were eventually chosen after full-text review. For studies on TORS, 61.3% of patients (84 out of 137) still survived at the last follow-up with a mean follow-up time of 23.20 months (range: 12.8-37.21 months). Severe intraoperative and postoperative complications have not been reported. No cases of TORS required a conversion to open surgery. Swallowing function was optimal postoperatively with only 6 patients eventually required a percutaneous endoscopic gastrostomy (PEG) for feeding. Disease-specific survival was taken as the parameter for the measurement of oncological outcomes. A total of 2 studies reported a disease-specific survival of 100% within their follow-up period of 1 and 1.5 years, respectively. Another 2 studies reported a 2-year DSS of 89 and 98%, respectively. A 5-year DSS of 100% in early stage and 74% in late stage were achieved in one study. Another study also reported a 5-year DSS of 91.7%. For studies of ELPS, a 5- and 3-year disease-specific survival of 100% were achieved in 2 studies. Patients who underwent ELPS had good postoperative swallowing function with no PEG placement. There were also no other fatal complications. Conclusions: Both TORS and ELPS for HPC provide satisfactory long-term oncological and functional outcomes improving postoperative quality of life of patients.

Survivin expression in head and neck squamous cell carcinomas is frequent and correlates with clinical parameters and treatment outcomes.

OBJECTIVES: Strong expression of survivin is associated with worse survival in many different tumours, and in cell culture, a correlation between radiation resistance and survivin expression can be seen. The potential of survivin expression as a prognostic/predictive marker or therapeutic target has not been examined in head and neck squamous cell carcinomas (HNSCC) yet. MATERIAL AND METHODS: Retrospective study of 452 tissue samples and clinical data from patients with squamous cell carcinomas of the larynx/hypopharynx (LSCC), oral cavity (OSCC) and oropharynx (OPSCC) treated in the University Medical Centre Hamburg-Eppendorf between 2002 and 2006. The expression patterns were detected by tissue microarray technique and correlated with clinical parameters (sex, age, tumour location, TNM 7th edition, grading, recurrence-free and overall survival). RESULTS: 222 OSCC, 126 OPSCC and 105 LSCC tumours of 118 females and 335 males with a mean follow-up of 41.3 months were examined. Survivin expression correlates with pN, cM, pT and overall survival. CONCLUSION AND CLINICAL RELEVANCE: The potential of survivin as a prognostic/predictive marker is very high. The findings have to be confirmed in a larger cohort of HNSCC esp. in those tumours treated primarily with radio/radiochemotherapy.

Robotic Thyroid Surgery: Current Perspectives and Future Considerations.

Robotic transaxillary thyroidectomy, pioneered in South Korea, is firmly established throughout the Far East but remains controversial in Western practice. This relates to important population differences (anthropometry and culture) compounded by the smaller mean size of thyroid nodules operated on in South Korea due to a national thyroid cancer screening programme. There is now level 2 evidence (including from Western World centres) to support the safety, feasibility, and equivalence of the robotic approach to its open counterpart in terms of recurrent laryngeal nerve injury, hypoparathyroidism, haemorrhage, and oncological outcomes for differentiated thyroid cancer. Moreover, robotic thyroidectomy has been shown to be superior to open surgery for certain patient-reported outcome measures, namely scar cosmesis and pain. Downsides include its high cost, longer operative time, and risk of complications not encountered in open thyroidectomy (brachial plexus neurapraxia). Careful patient selection is paramount as this procedure is not for every patient, surgeon, or hospital. It should only be undertaken by high-volume surgeons operating as part of a multidisciplinary robotic team in specialised centres. Novel robotic approaches utilising the retroauricular and transoral routes for thyroidectomy have recently been described but further studies are required to establish their respective role in modern thyroid surgery.

Novel approach to magnetic resonance imaging of epileptic dogs - T2 relaxometry of the brain with emphasised hippocampus.

Hippocampal sclerosis is the most common imaging finding of intractable human epilepsy, and it may play an important role in canine and feline epileptogenesis and seizure semiology, too. The magnetic resonance imaging (MRI) criteria of hippocampal sclerosis are T2 hyperintensity, shrinkage and loss of internal structure. The detection of these changes is often challenging by subjective visual assessment of qualitative magnetic resonance (MR) images. The recognition is more reliable with quantitative MR methods, such as T2 relaxometry. In the present prospective study including 31 dogs with idiopathic epilepsy and 15 control dogs showing no seizure activity, we compared the T2 relaxation times of different brain areas. Furthermore, we studied correlations between the hippocampal T2 values and age, gender and skull formation. We found higher hippocampal T2 values in the epileptic group than in the control; however, these findings were not statistically significant. No correlations were found with age, gender or skull formation. In the individual analysis six epileptic dogs presented higher hippocampal T2 relaxation times than the cut-off value. Two of these dogs were also evaluated as abnormal in the visual assessment. Individual analysis of hippocampal T2 relaxation times may be a helpful method to understand hippocampal involvement in canine epilepsy.

Survival analysis of 287 oropharyngeal squamous cell carcinoma patients in a single institution: a retrospective comparison of two consecutive time intervals with surgical and conservative treatment approaches.

This study is a retrospective analysis of clinico-pathological data to investigate survival rates of patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with different modalities in a single academic head and neck cancer center in different time intervals. Altogether, 287 patients with OPSCC were included in this comparison. Patients were analysed during two different treatment periods: Group 1 included patients treated mainly with primary surgery ± adjuvant radio(chemo)therapy between 2002 and 2007, while Group 2 included patients treated with organ/function-preservation protocols if indicated. Main outcome measures were overall survival (OS) and recurrence-free survival (RFS). Between 2002 and 2007, early-stage OPSCC showed a 5-year OS of 75% compared to that of 86% between 2008 and 2013. Locally advanced OPSCC showed a 5-year OS of 66% between 2002 and 2007 compared to that of 74% between 2008 and 2013. RFS in early-stage OPSCC was 48% between 2002 and 2007 in contrast to that of 77% between 2008 and 2013. With locally advanced OPSCC, RFS was 55% between 2002 and 2007 compared to that of 56% between 2008 and 2013. These differences were statistically not significant. The OS and RFS remained generally unchanged over the analysed time period. There was no significant difference in the outcomes with regards to HPV status and to their treatment modality.

Facial mimetic, cosmetic, and functional standardized assessment of the facial artery musculomucosal (FAMM) flap.

OBJECTIVE: To objectively assess donor site morbidity after harvesting the facial artery musculomucosal flap. Use of the FAMM-flap in oral cavity reconstruction remains sporadic. This case series describes our newly developed standardized assessment of this flap in a floor of mouth (FOM) reconstructive setting. METHODS: Standardized postoperative assessment of the FAMM flap for donor site wound complications, functional, facial mimetic and oncologic outcomes. RESULTS: There were no wound complications. Oral competence remained intact, tongue mobility was good to excellent, average word articulation score was 98%, and mimetic function excellent in all patients. Three patients experienced ipsilateral upper lip anesthesia, and five patients were noted to have slight dysfunction of the orbicularis oris resulting in a loss of lip height at rest. CONCLUSION: The FAMM flap is a reliable option for reconstruction of ablative defects of the FOM, and should be considered a workhorse flap for oral cavity defects. Unlike the submental island flap, a complete level I dissection may be concurrently performed without compromising the vascular supply to the FAMM flap.

[Maximizing nodal yield while minimizing surgical morbidity: the appropriate neck dissection]. / A nyaki dissectiók onkológiai hozamának maximalizálása a sebészi morbiditás egyideju minimalizálása mellett.

Cervical regional lymphadenectomy, also known as neck dissection, is a fundamental procedure in head and neck surgery. Its evolution over 110 years resulted in a great deal of confusion in the literature and in clinical practice, due to the heterogenicity in training, classification and surgical techniques, which makes outcomes comparability virtually impossible. The authors aim to clarify this situation in a structured manner, in order to facilitate communication among all specialists involved in multidisciplinary head and neck cancer care. The ultimate goal is to make sure that each and every head and neck cancer patient receives their optimal treatment. Review of the history and literature with statistical comparison of the two mainstraim methods regarding their nodal yield results. The applied surgical technique has a significant impact on nodal yield. An appropriate surgical concept achieves maximum oncologic benefit, minimum surgical morbidity with optimized adjuvant indications. Orv. Hetil., 2016, 157(47), 1871-1879.

Perspectives in chemosensitivity and chemoresistance assays and their implementation in head and neck cancer.

Therapeutic options for patients with head and neck squamous cell carcinoma include surgery, radiation and chemotherapy. The latter plays a major role in the treatment selection of recurrent, metastatic or therapy resistant tumours, these being some of the major challenges in head and neck oncology. For these patients, chemosensitivity and chemoresistance assays would be paramount to identify their individual therapy options. In this review, seven common assays will be described and discussed in the context of several studies. Further, a new assay will also be presented, currently being validated in a European Union funded project. Comparisons will be drawn to evaluate the sensitivity and specificity of these assays in identifying individual treatment options, and their potential implementation in head and neck malignancies will be discussed. There is an unmet demand for the development of ex vivo diagnostic tools that may predict response in head and neck cancer on the way towards an individualized treatment for these patients.

Automatic periodic stimulation of the vagus nerve during single-incision transaxillary robotic thyroidectomy: Feasibility, safety, and first cases.

BACKGROUND: Automatic periodic stimulation (APS) of the vagus nerve during thyroid surgery may provide the patient with increased safety to prevent impending thermal or stretch-related injury to the recurrent laryngeal nerve (RLN). METHODS: Vagal stimulation would be of particular interest in remote access robotic thyroid surgery, where the RLN may be exposed to more conducted heat because of the exclusive use of the Harmonic scalpel. Using APS, the console surgeon may adjust the dissection technique according to the signal changes to avoid impending thermal damage to the nerve. RESULTS: In 2 transaxillary robotic thyroidectomy cases, we placed the vagus electrode onto the ipsilateral vagus trunk through the single-incision transaxillary access before docking the da Vinci robot. APS of the ipsilateral nerve has been conducted without complications. CONCLUSION: APS of the ipsilateral vagus is feasible and safe during transaxillary robotic thyroidectomy, and may contribute to prevent impending thermal injury to the RLN.

Endpoints and cutpoints in head and neck oncology trials: methodical background, challenges, current practice and perspectives.

This article reviews the methodical and statistical basics of designing a trial, with a special focus on the process of defining and choosing endpoints and cutpoints as the foundations of clinical research, and ultimately that of evidence-based medicine. There has been a significant progress in the treatment of head and neck cancer in the past few decades. Currently available treatment options can have a variety of different goals, depending e.g. on tumor stage, among other factors. The outcome of a specific treatment in clinical trials is measured using endpoints. Besides classical endpoints, such as overall survival or organ preservation, other endpoints like quality of life are becoming increasingly important in designing and conducting a trial. The present work is based on electronic research and focuses on the solid methodical and statistical basics of a clinical trial, on the structure of study designs and on the presentation of various endpoints.

Decision management in transoral robotic surgery: Indications, individual patient selection, and role in the multidisciplinary treatment for head and neck cancer from a European perspective.

BACKGROUND: Transoral robotic surgery (TORS) has become an accepted first-line treatment for T1 and T2 head and neck squamous cell carcinoma (HNSCC). The growing popularity of this procedure is the result of mounting skepticism as to the survival and quality of life (QOL) benefits of primary chemoradiation over definitive surgery, the rising incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) in progressively younger patients, and the advantages of TORS over transoral laser microsurgery (TOLM) and open surgery. METHODS: The authors use their experience and data gained from the TORS-based management of >100 patients to establish a systematic approach to the use of TORS in HNSCC. RESULTS: This approach is constructed on a framework which goal is to select the primary treatment option that is most likely to reduce morbidity while preserving function and maintaining oncologic safety. CONCLUSION: A consensus regarding the indications of TORS and its role in the multidisciplinary management of HNSCC is to be established. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2190-E2196, 2016.

Molecular targeting in combination with platinum-based chemoradiotherapy in head and neck cancer treatment.

BACKGROUND: Significant evidence exists supporting the use of platinum-based chemoradiotherapy (CRT) as a primary curative approach in locoregionally advanced head and neck cancer (HNSCC). Despite these aggressive protocols, 70% of patients die within 5 years because of locoregional recurrence or distant metastasis. To increase the response and survival of patients with HNSCC, CRT has been combined with molecular agents targeting distinct kinases. METHODS: This study was performed using a systematic literature review. RESULTS: The effect of targeted therapy on patient survival in the context of CRT remains controversial, with toxicities tending to be more severe but still acceptable. CONCLUSION: Supplementing CRT with target therapeutics might only improve survival in some patients with locally advanced HNSCC. Therefore, future studies must address the underlying biological mechanisms that can have an impact on treatment response. Such knowledge is essential in order to facilitate the effective and personalized treatment of patients with locally advanced HNSCC by combining CRT and targeted therapy. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2173-E2181, 2016.

The impact of surgical technique on neck dissection nodal yield: making a difference.

The nodal yield of neck dissections is an independent prognostic factor in several types of head and neck cancer. The authors aimed to determine whether the applied dissection technique has a significant impact on nodal yield. This is a single-institution, prospective study with internal control group (level of evidence: 2A). Data of 150 patients undergoing 223 neck dissections between February 2011 and March 2013 have been collected in a comprehensive cancer centre. Eighty-two patients underwent neck dissection with unwrapping the cervical fascia from lateral to medial, while 68 patients were operated without specifically unwrapping the fascia, in a caudal to cranial fashion. The standardised, horizontal neck dissection technique along the fascial planes resulted in a significantly higher nodal count in Levels I, II, III and IV, as well as in terms of overall nodal yield (mean: n = 22.53) than that of the vertical dissection applied in the control group (mean: n = 15.00). This is the first publication showing a direct correlation between neck dissection nodal yield and surgical technique. Therefore, it is paramount to optimise the applied surgical concept to maximise the oncological benefit.