Biases related to periostin levels in chronic rhinosinusitis with nasal polyposis: a systematic review.

BACKGROUND: The role of periostin in the pathophysiology of chronic rhinosinusitis with nasal polyposis (CRSwNP) has been debated in the literature, with several authors proposing periostin as a potential biomarker or theurapeutical target. However, the mechanisms regulating the systematic or local periostin production in both CRSwNP patients and controls remain elusive. METHODOLOGY: Any factors reported to affect periostin expression in polyp tissue samples, nasal mucosa samples, serum and nasal secretions were considered as primary outcomes in this systematic review. Interactions or synergistic effects between bias factors were considered as secondary outcomes. RESULTS: Eosinophilic CRSwNP, large polyp size and radiological severity were found to be high-risk, positive bias factors for periostin levels in polyp tissue samples, while the role of atopy and asthma has been debated. Immunotherapy and eosinophilic endotype were identified as biases for serum periostin measurements, while steroids and non-steroidal anti-inflammatory drug exacerbated respiratory disease remain of unclear risk. Bronchal asthma, eosinophilic endotype and immunotherapy have been reported to bias periostin measurements in nasal secretions. CONCLUSIONS: The relevant literature is extremely limited and little is actually known about the intrinsic or extrinsic factors affecting periostin measurements. The synthesis of the existing literature should be done with cautiousness.

Matrix metalloproteinases and chronic rhinosinusitis with nasal polyposis. Unravelling a puzzle through a systematic review.

BACKGROUND: The expression of metalloproteinases (MMPs) in chronic rhinosinusitis with nasal polyposis (CRSwNP) was reviewed in order to investigate their possible use as therapeutical targets and/or biomarkers. METHODOLOGY: The differences between CRSwNP and normal controls or CRS without NP, as well as the effects of various treatments on MMPs, tissue inhibitors of MMPs (TIMPs) and MMP/TIMP ratios were considered as primary outcomes. Additional factors reported to affect MMP expression levels were noted as secondary outcomes. Data regarding inflammatory subtypes, patients’ clinical characteristics, controls, laboratory method(s) and origin of samples were also pooled. Studies on 10 or fewer patients or on specimens other than nasal and serum were excluded. RESULTS: Forty-three studies were included. Tissue sample origin, allergic rhinitis, smoking, infection, medication intake and primary or recurrent disease should be considered as confounding factors for MMP levels. MMP-1 and -7 were consistently found to be significantly higher in CRSwNP patients than controls. CRSwNP endotypes with distinctly different inflammation patterns seem to present similar MMP-related remodelling patterns. CONCLUSIONS: The existing literature has revealed several population and methodology related confounding factors and remains inconclusive regarding the roles of MMPs in CRSwNP pathophysiology and their possible clinical usefulness as biomarkers and therapeutical targets.

New European Academy of Allergy and Clinical Immunology definition on pollen season mirrors symptom load for grass and birch pollen-induced allergic rhinitis.

BACKGROUND: The use of allergen immunotherapy (AIT) for allergic rhinitis and its clinical efficacy in clinical trials depends on the effective determination of pollen allergen exposure time periods. We evaluate pollen data from Germany to examine the new definitions on pollen season and peak pollen period start and end as proposed by the European Academy of Allergy and Clinical Immunology (EAACI) in a recently published Position Paper. The aim was to demonstrate the ability of these definitions to mirror symptom loads for grass and birch pollen-induced allergic rhinitis based on real-life data. METHODS: Data coming from four pollen monitoring stations in the Berlin and Brandenburg area in Germany and for 3 years (2014-2016) were used to investigate the correlation of season definitions, birch and grass pollen counts and total nasal symptom and mediation scores as reported by patients in "Patients Hay fever Diaries" (PHDs). After the identification of pollen periods on the basis of the EACCI criteria, a statistical analysis was employed, followed by a detailed graphical investigation. RESULTS: The analysis revealed that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to symptom loads for grass and birch pollen-induced allergic rhinitis reported by patients in PHDs. CONCLUSION: Based on our analysis, the validity of the EAACI definitions on pollen season is confirmed. Their use is recommended in future clinical trials on AIT as well as in daily routine for optimal patient care.

Objective assessment of subjective tinnitus through contralateral suppression of otoacoustic emissions by white noise; suggested cut-off points.

OBJECTIVE: Normative otoacoustic emission (OAE) suppression values are currently lacking and the role of cochlear efferent innervation in tinnitus is controversial. The aim of this study was to investigate the association between tinnitus and medial olivocochlear bundle (MOCB) malfunction. Potential suppression amplitude cut-off criteria that could differentiate participants with tinnitus from those without were sought. DESIGN: Mean suppression amplitudes of transient evoked OAEs and distortion product OAEs by contralateral white noise (50 dBSL) were recorded. Six mean suppression amplitudes criteria were validated as possible cut-off points. STUDY SAMPLE: The population consisted of normal hearing (n = 78) or presbycusic adults (n = 19) with tinnitus or without (n = 28 and 13, respectively) chronic tinnitus (in total, n = 138 78 females/60males, aged 49 ± 14 years). RESULTS: Participants with mean suppression values lower than 0.5-1 dBSPL seem to present a high probability to report tinnitus (specificity 88-97%). On the other hand, participants with mean suppression values larger than 2-2.5dBSPL seem to present a high probability of the absence of tinnitus (sensitivity 87-99%). Correlations were stronger among participants with bilateral presence or absence of tinnitus. CONCLUSIONS: This study seem to confirm an association between tinnitus and low suppression amplitudes (<1 dBSPL), which might evolve into an objective examination tool, supplementary to conventional audiological testing.

Chondrosarcoma treated with transoral near total resection of the cricoid.

INTRODUCTION: Chondrosarcomas of the larynx are usually slow-growing tumours. Their prognosis is reportedly unaffected by local tumour recurrence. Nevertheless, total laryngectomy is often performed in fear that resection of the posterior lamina of the cricoid cartilage may cause laryngeal collapse and stenosis. Transoral laser surgery (TLS) is not considered among the treatment options. This case report supports the feasibility of a radical yet organ- and function-preserving tumour excision using TLS. CASE REPORT: A female patient presented with dyspnoea due to an extensive low-grade laryngeal chondrosarcoma. TLS treatment involved total resection of the posterior lamina of the cricoid cartilage. The patient was decannulated 8 months later with normal swallowing and satisfactory voice quality, which allowed her to have a normal personal and social life. CONCLUSION: TLS excision of the posterior lamina of the cricoid cartilage seems to be a feasible and radical yet function- and organ-preserving technique with minimal morbidity.

Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action.

Non-competitive NMDA receptor antagonists are widely used as pharmacological models of schizophrenia due to their ability to evoke the symptoms of the illness. Likewise, serotonergic hallucinogens, acting on 5-HT(2A) receptors, induce perceptual and behavioural alterations possibly related to psychotic symptoms. The neurobiological basis of these alterations is not fully elucidated. Data obtained in recent years revealed that the NMDA receptor antagonist phencyclidine (PCP) and the serotonergic hallucinogen 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane; DOI) produce a series of common actions in rodent prefrontal cortex (PFC) that may underlie psychotomimetic effects. Hence, both agents markedly disrupt PFC function by altering pyramidal neuron discharge (with an overall increase) and reducing the power of low frequency cortical oscillations (LFCO; < 4 Hz). In parallel, PCP increased c-fos expression in excitatory neurons of various cortical areas, the thalamus and other subcortical structures, such as the amygdala. Electrophysiological studies revealed that PCP altered similarly the function of the centromedial and mediodorsal nuclei of the thalamus, reciprocally connected with PFC, suggesting that its psychotomimetic properties are mediated by an alteration of thalamocortical activity (the effect of DOI was not examined in the thalamus). Interestingly, the observed effects were prevented or reversed by the antipsychotic drugs clozapine and haloperidol, supporting that the disruption of PFC activity is intimately related to the psychotomimetic activity of these agents. Overall, the present experimental model can be successfully used to elucidate the neurobiological basis of schizophrenia symptoms and to examine the potential antipsychotic activity of new drugs in development.

Immunohistochemical studies of wound healing after monopolar electrocautery and ultrasound submucosal inferior nasal turbinate reduction in sheep.

BACKGROUND: Extracellular matrix (ECM) proteins such as fibronectin and collagen III, enzymes such as matrix metalloproteinases and macrophages have been demonstrated to intervene in nasal and paranasal sinuses wound healing. AIM OF THE STUDY: To compare concentration of ECM proteins, enzymes and the recruitment of macrophages during wound repair after monopolar electrocautery in contrast with ultrasound submucosal surgical tissue reduction of inferior nasal turbinate (INT) tested in sheep. MATERIALS AND METHODS: Prospective controlled study in sheep. Immunostaining for collagen III, fibronectin, CD68 and matrix metalloproteinase-9 (MMP9) was applied in tissue specimens of INT mucosa after monopolar electrocoagulation (MEC) and ultrasound tissue reduction (UTR). Twelve INTs were studied 1, 3 and 8 weeks post-operatively in each interventional group (MEC and UTR) and 5 INTs were studied in animals of the control group (without surgery). The immunoreactivity was quantitatively graded between 0% to 100% immunoreactivity by a blinded senior pathologist. RESULTS: At the end of the study period collagen III, fibronectin and MMP9 were increased in both groups compared to the levels of the control group. When compared to control group, CD68 immunoreactivity was found higher in MEC group but not in UTR group. Fibronectin subepithelial immunoreactivity exhibited a substantial negative correlation with mucosal epithelial cell necrosis, a substantial positive correlation with fibrosis in MEC-treated specimens and a significant positive correlation with sinusoid engorgement in UTR-treated specimens. Collagen III tissue immunoreactivity showed a particularly significant negative correlation with sinusoid engorgement in MEC-treated specimens. CONCLUSION: Correlation of fibronectin and collagen III immunoreactivity to histopathologic findings suggests different ECM repair processes between MEC and UTR turbinate tissue reduction. The use of CD68 and MMP9 provides additional clues to the mode of actions of these techniques and to the molecular and cellular events of the nasal mucosa wound healing process.

Positive and negative post stapedotomy effects on cervical VEMP recordings; a STROBE analysis.

AIMS: The primary goal of the present study was to compare the pre- and post-stapedotomy elicitation and waveform characteristics of both air- and bone-conduction (AC-, BC-) cervical vestibular evoked myogenic potentials (cVEMPs) through an individualized approach. A possible association between audiological characteristics, such as AC- and BC- pure tone audiometry thresholds and air-bone gap and the production of cVEMPs before and after stapedotomy was also investigated. MATERIAL AND METHODS: Twenty-five ears were subjected to full audiological evaluation as well as AC- and BC-cVEMPs pre- and post-stapedotomy. Four subgroups were studied; consistently present/absent, post-operatively disappeared and restored cVEMPs. RESULTS: Post-stapedotomy changes in cVEMP elicitability did not reach significance for either AC-cVEMP (OR=5.41, 95% CI 0.88-33.36, P=0.06) or BC-cVEMP (OR=2.40, 95% CI 0.42-13.60, P=0.3). Normal or abnormal AC-cVEMPs were equally subject to post-operative changes (OR=1.95, 95% CI 0.32-12.01, P=0.5), as were BC-cVEMPs (OR=3.75, 95% CI 0.66-21.25, P=0.1). Neither the audiological characteristics nor the surgical outcome, in terms of ABG results, were relevant to the presence or absence of AC- and BC-cVEMPs before or after stapedotomy. CONCLUSIONS: The presumed changes brought to the sacculus by stapedotomy are minor and beyond the diagnostic abilities of either AC-cVEMPs or BC-cVEMPs, both in terms of cVEMPs elicitability and waveform characteristics. In individual cases, however, which may deserve further investigation, cVEMPs may reappear or disappear after stapedotomy probably following minor changes toward a lower or higher vestibular system resistance for pressure and sound transmission.

Comparison of clinical and histopathological evaluation of tonsils in pediatric and adult patients.

The aim of this study was to determine clinical features that could predict the presence of tonsillar malignancy in children and adults. A retrospective review of the histopathologic reports of the children, who underwent tonsillectomy (753 cases) during the past 16 years (January 1991-December 2006) in a busy district general hospital, was undertaken. We compared the results to the pre-operative data of the patients, for risk factors of malignancy. Such proposed risk factors were tonsillar asymmetry, palpable firmness, visible lesions, neck adenopathy, history of malignancy, and systemic symptoms. The same data (history, risk factors and histopathologic results) were reviewed for an adult group (>16 years old, 1,027 cases) who underwent tonsillectomy during that period, and the results of the two groups were compared. In the pediatric group only one case was diagnosed as lymphoma (0.13%) and the rest as chronic inflammation (47%), reactive tonsil tissue (26%), lymphoid hyperplasia (19%) and actinomycosis (8%). In the lymphoma case, the diagnosis was suspected preoperatively by history and clinical manifestations. In the adult group, there were 21 cases of malignancy out of 1,027 cases (2.04%), again with one or more positive risk factors in the pre-surgery history. Based on our review, it is concluded that histopathology of tonsillectomy is not necessary in children unless there is clinical suspicion based on preoperative findings. A protocol based on proposed risk factors which may be predictive of possible malignancy can be used as a guide to intraoperative histology.

Cancer survival in England and Wales at the end of the 20th century.

Survival has risen steadily since the 1970s for most cancers in adults in England and Wales, but persistent inequalities exist between those living in affluent and deprived areas. These differences are not seen for children. For many of the common adult cancers, these inequalities in survival (the 'deprivation gap') became more marked in the 1990s. This volume presents extended analyses of survival for adults diagnosed during the 14 years 1986-1999 and followed up to 2001, including trends in overall survival in England and Wales and trends in the deprivation gap in survival. The analyses include individual tumour data for 2.2 million cancer patients. This article outlines the structure of the supplement - an article for each of the 20 most common cancers in adults, followed by an expert commentary from one of the leading UK clinicians specialising in malignancies of that organ or system. The available data, quality control and methods of analysis are described here, rather than repeated in each of the 20 articles. We open the discussion between clinicians and epidemiologists on how to interpret the observed trends and inequalities in cancer survival, and we highlight some of the most important contrasts in these very different points of view. Survival improved substantially for adult cancer patients in England and Wales up to the end of the 20th century. Although socioeconomic inequalities in survival are remarkably persistent, the overall patterns suggest that these inequalities are largely avoidable.

Benign paroxysmal positional vertigo of the anterior semicircular canal: atypical clinical findings and possible underlying mechanisms.

Anterior semicircular canal (ASC) lithiasis is uncommon and usually self-treated. In the rare cases when such patients seek medical advice, diagnosis requires careful consideration of the patient's symptoms and the clinical characteristics of the nystagmus triggered by the Dix-Hallpike (D-H) examination. In this study, two atypical cases of ASC benign paroxysmal positional vertigo (BPPV) are presented and the relevant literature is reviewed. Regardless of their unique symptoms, both participants in this study were diagnosed with lithiasis of the left ASC. The clinical manifestations of ASC BPPV may differ significantly from typical symptoms seen in the more common posterior semicircular canal BPPV. The possible mechanisms responsible for this intriguing variance, as well as guidelines for diagnosing the affected side, are discussed.

Objective assessment of subjective tinnitus through contralateral suppression of otoacoustic emissions by white noise: effects of frequency, gender, tinnitus bilaterality and age.

SUMMARY: Accumulating evidence seems to support an association between tinnitus and medial olivocochlear bundle (MOCB) dysfunction. Most studies use patient/control comparisons to support this correlation. The aim of this study was to investigate the hypothesis in a substantially different way and evaluate the roles of gender, age, frequency and tinnitus bilaterality as possible confounding factors. The population consisted of 78 normal hearing patients with chronic tinnitus, 28 normal hearing controls, 19 presbycousic tinnitus patients and 13 presbycousic controls (n = 276 ears). Mean suppression amplitudes of transient evoked otoacoustic emissions (TEOAEs) and distortion product OAEs (DPOAEs) by contralateral white noise (50 dB SPL) were computed. Mean suppression values < 1 dB SPL or < 2 dB SPL were validated as positive test results. Overall suppression (OS) values < 1 dB SPL were qualified as a diagnostic test of moderate positive predictive value for both DPOAEs and TEOAEs, while OS values < 2 dB SPL were found to be of large negative predictive value for DPOAEs and moderate for TEOAEs. Mean suppression values (for all frequencies, OS) are of higher diagnostic value than suppression values corresponding to either lower (1-2 kHz) or higher frequencies (2.8-4 kHz for TEOAEs and 2.8-6 kHz for DPOAEs). After excluding patients with unilateral tinnitus from the analysis, correlations were found to be stronger. Useful correlations were also attributed for all age groups < 61 years. In females, OAE suppression seems to have a stronger positive predictive value, while in males it seems to have a stronger negative predictive value. OAE-based assays of MOCB function as an objective diagnostic tool for subjective tinnitus might deserve further investigation. Tinnitus uni- or bi-laterality is a confounding factor, which probably confirms the observation that defective function of the MOCB usually applies to the contralateral ear as well. Gender is an additional confounding factor, while correlations can be verified for all age groups < 61 years old.

Effects of Hallucinogens on Neuronal Activity.

Hallucinogens evoke sensory, perceptual, affective, and cognitive effects that may be useful to understand the neurobiological basis of mood and psychotic disorders. The present chapter reviews preclinical research carried out in recent years in order to better understand the action of psychotomimetic agents such as the noncompetitive NMDA receptor (NMDA-R) antagonists and serotonergic hallucinogens. Our studies have focused on the mechanisms through which these agents alter cortical activity. Noncompetitive NMDA-R antagonists, such as phencyclidine (PCP) and MK-801 (dizocilpine), as well as the serotonergic hallucinogens DOI and 5-MeO-DMT, produce similar effects on cellular and population activity in prefrontal cortex (PFC); these effects include alterations of pyramidal neuron discharge (with an overall increase in firing), as well as a marked attenuation of the low frequency oscillations (0.2-4 Hz) to which neuronal discharge is coupled in anesthetized rodents. PCP increases c-fos expression in excitatory neurons from various cortical and subcortical areas, particularly the thalamus. This effect of PCP involves the preferential blockade of NMDA-R on GABAergic neurons of the reticular nucleus of the thalamus, which provides feedforward inhibition to the rest of thalamic nuclei. It is still unknown whether serotonergic hallucinogens also affect thalamocortical networks. However, when examined, similar alterations in other cortical areas, such as the primary visual cortex (V1), have been observed, suggesting that these agents affect cortical activity in sensory and associative areas. Interestingly, the disruption of PFC activity induced by PCP, DOI and 5-MeO-DMT is reversed by classical and atypical antipsychotic drugs. This effect suggests a possible link between the mechanisms underlying the disruption of perception by multiple classes of hallucinogenic agents and the therapeutic efficacy of antipsychotic agents.

Hydatid cyst in the duct of the submandibular gland.

The case of a hydatid cyst located in the duct of Wharton of a 56-year-old farmer is reported not only because of the unusual location of the disease, but also because the clinical manifestations and surgical findings of the hydatid cyst strongly resembled those of a salivary calculus in the duct of Wharton. The patient presented with a non-painful swelling of the right submandibular region. The mass, which appeared 5 years before seeking medical advice, augmented progressively during the first year after its onset and remained stable during the next 4 years. The subsequent surgical excision of the mass was uneventful and a round mass, which was palpated intraoperatively in the duct of Wharton was assumed to be a sialolith. The diagnosis for a hydatid cyst of the duct of Wharton was made by histological examination. Although salivary calculus is the most common finding in cases of obliteration of the duct of Wharton, histological examination of the surgically excised submandibular gland may reveal benign tumours. In extremely rare cases where hydatid cysts are located in the cervicofacial area, a detailed further diagnostic procedure is required in order to diagnose possible involvement of other organs.

Neurotoxicity of vincristine on the medial olivocochlear bundle.

OBJECTIVE: Vincristine is a well known neurotoxic chemotherapeutic agent. Dose dependent and cumulative peripheral neuropathy is the main dose limiting side effect of chemotherapy with vincristine. The mechanisms responsible for the neurotoxic effects of vincristine have not yet been fully understood. This prospective study was directed at determining whether vincristine treatment interferes with the function of the medial olivocochlear bundle. DESIGN: Fifteen children suffering from leukemia were subjected to tympanogram, stapedial muscle reflex, pure tone audiometry and transient evoked otoacoustic emissions (TEOAEs) in the absence and presence of contralateral white noise on day 1 and on day 22 of treatment with vincristine. The function of the medial olivocochlear bundle was assessed by the phenomenon of suppression of otoacoustic emissions by contralateral application of white noise. RESULTS: The study revealed a statistically significant decrease of contralateral suppression amplitudes in all cases after three sessions of chemotherapy with vincristine. On the contrary no alterations were observed in pure tone audiometry thresholds. A non-significant decrease of the mean TEOAEs' amplitudes was also noted. When analyzed by frequency, however, this decrease reached the level of statistical significance at two frequencies. CONCLUSION: Vincristine treatment seems to exert a neurotoxic effect on the efferent olivocochlear system, which takes place early in the course of chemotherapy. This is a new aspect to be added to the possible mechanisms underlying the toxicity of vincristine in the auditory periphery. Whether changes in efferent function might contribute to understanding the mechanisms of neurotoxicity caused by vincristine, or find any clinical application as a predictor or early detector of neurological side effects of vincristine still remains to be seen.

Long-term effects of chemotherapy for acute lymphoblastic leukemia on the medial olivocochlear bundle: effects of different cumulative doses of gentamicin.

OBJECTIVE: The treatment of acute lymphoblastic leukemia (ALL) often combines a neurotoxic chemotherapeutic protocol such as Berlin-Frankfurt-Munster-95 (BFM-95) with gentamicin, an antibiotic known to have an early and quickly reversed impact on olivocochlear reflex in animal studies. This study investigates whether this combination has any long-term side effects on the medial olivocochlear bundle (MOCB). METHODS: In all 47 children of the study suppression of distortion product otoacoustic emissions (DPOAEs) by contralateral application of white noise (WN) was used to assess the function of the MOCB. The population was divided into three groups depending on the time interval between the end of therapy and examination. The group examined shortly after chemotherapy included 12 children who had received low gentamicin doses (less than 13 days). The group evaluated 2 years after therapy involved another 12 children who had required medium gentamicin doses (more than 13, less than 23 days). The group examined 3 years after therapy included a subgroup of 12 children to whom low gentamicin doses were infused and another 11 children with high gentamicin doses (more than 23 days). RESULTS: Three years after therapy the olivocochlear reflex was efficiently produced in both subgroups of low and high gentamicin doses. Two years after therapy, contralateral WN induced increase of DPOAEs at 4 of the 12 examined frequencies. Shortly after therapy, WN increased, instead of suppressing, DPOAEs at five frequencies. CONCLUSION: This abnormal result of contralateral noise application perceived as impaired cochlear efferent innervation may indicate that ALL-BFM-95 exerts a toxic effect on the MOCB, which is slowly reversed within the first 3 years after chemotherapy and does not seem to be affected in the long term by different cumulative doses of gentamicin.

Prevention of 5-fluorouracil-related stomatitis by oral cryotherapy: a randomized controlled study.

Stomatitis is a common adverse effect of intravenously infused 5-fluorouracil (5FU). Although there are encouraging studies about the preventive role of oral cryotherapy in stomatitis induced by intravenous administration of 5FU, this simple and cost-effective method is not part of clinical practice. This prospective randomized study investigates whether oral cryotherapy alleviates 5FU-induced stomatitis. Thirty six patients, included in the cryotherapy group, were instructed to hold ice cubes in their oral cavity, shortly before, during and shortly after the infusion of 5FU. Both mean physician and patient-graded stomatitis of our cryotherapy group were compared with those of a control group (40 patients) and were found significantly reduced for all three chemotherapy cycles. The percentage of patients who were free from oral toxicity was significantly higher in the cryotherapy group in all three chemotherapy cycles, as judged both by patients and physicians. The results of this study encourage the use of cryotherapy in patients receiving 5FU in alleviating stomatitis by using a side-effect-free, easy to perform and inexpensive measure, which does not interfere with the efficacy of antineoplastic agents.

Effect of sugammadex versus neostigmine/atropine combination on postoperative cognitive dysfunction after elective surgery.

This study aimed to assess the effects of sugammadex and neostigmine/atropine on postoperative cognitive dysfunction (POCD) in adult patients after elective surgery. A randomised, double-blind controlled trial was carried out on 160 American Society of Anesthesiologists physical status I to III patients who were >40 years. The Mini-Mental State Evaluation, clock-drawing test and the Isaacs Set test were used to assess cognitive function at three timepoints: 1) preoperatively, 2) one hour postoperatively, and 3) at discharge. The anaesthetic protocol was the same for all patients, except for the neuromuscular block reversal, which was administered by random allocation using either sugammadex or neostigmine/atropine after the reappearance of T2 in the train-of-four sequence. POCD was defined as a decline ≥1 standard deviation in ≥2 cognitive tests. The incidence of POCD was similar in both groups at one hour postoperatively and at discharge (28% and 10%, in the neostigmine group, 23% and 5.4% in the sugammadex group, P=0.55 and 0.27 respectively). In relation to individual tests, a significant decline of clock-drawing test in the neostigmine group was observed at one hour postoperatively and at discharge. For the Isaacs Set test, a greater decline was found in the sugammadex group. These findings suggest that there are no clinically important differences in the incidence of POCD after neostigmine or sugammadex administration.

Systematic review on T3 laryngeal squamous cell carcinoma; still far from a consensus on the optimal organ preserving treatment.

OBJECTIVE: The optimal treatment of patients with T3 laryngeal carcinoma is controversially challenged by open partial laryngectomies (OPL), transoral laser microsurgery (TLM) and radiation therapy alone (RT) or combined with chemotherapy (ChRT). Treatment guidelines, experts' opinions and clinical studies are highly contradictory. The aim of this study is to compare the primary outcomes of the available treatment methods and identify the sources of variance among studies. METHODS: A review of the literature published in the time period 2003-2015 was conducted via the PubMed database (www.pubmed.org) and Scopus database (www.scopus.com) with the search terms "T3 laryngeal squamous cell cancer treatment". Data from clinical studies involving patients with T3 laryngeal cancer (n > 10) subjected to TLM, OPL, ChRT or RT, were pooled. In the absence of controlled studies, prospective and retrospective clinical trials with minimum 5-year follow-up were acceptable, provided that they included a description of patient eligibility criteria, so as to exclude studies with serious selection bias. RESULTS: Literature lacks studies with homogenous populations regarding TNM staging, preoperative/postoperative treatment or anatomical subsite. This raises substantial controversies and prohibits the conduction of a meta-analysis. Data for qualitative analysis were pooled from 8 studies (n = 1226). OPL and TLM both offer patients high survival and organ preservation rates. Preoperative induction chemotherapy seems to significantly compromise overall survival. CONCLUSIONS: Multicenter studies referring to homogenous populations, at least regarding staging and anatomical subsite, are needed. No safe conclusions can be drawn given the heterogeneity in patient cohorts, study design and evaluation of results in the existing literature.