Screening olfaction under dupilumab in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently leads to olfactory dysfunction. This study aimed to assess the impact of dupilumab on CRSwNP patients, focusing on olfactory outcomes and potential correlations with other clinical factors. METHODS: CRSwNP patients eligible for dupilumab therapy received subcutaneous Dupixent® injections every two weeks (300mg/2ml dupilumab). The 12-item Sniffin' Sticks Test (SST-12), fractional exhaled nitric oxide (FeNO) and Nasal Polyp Score (NPS) were assessed at baseline and after one, three, and six months. Patients also completed the Sino-Nasal Outcome Test (SNOT-22) weekly. RESULTS: 26 CRSwNP patients were included. After one month, dupilumab led to substantial reductions in FeNO, SNOT scores, andNPS, whereas SST-12 scores improved significantly only after three months. A shift toward normosmia occurred, with 81% achieving normosmia after six months, and a drop in anosmia prevalence to 9.5%. Significant negative correlations between olfaction (SST-12) and polyp severity (NPS) at baseline and after six months were found, while no significant correlations were observed between SST-12 and FeNO or SNOT scores. Age did not correlate with olfaction. CONCLUSIONS: Dupilumab demonstrated efficacy in restoring olfaction in CRSwNP patients. Reaching normosmia in over 80% ofpatients after six months of treatment underscores the drug's effectiveness in managing this challenging symptom.

Overall and disease-specific survival of sinonasal adenoid cystic carcinoma: a systematic review and meta-analysis.

This meta-analysis aims to investigate the outcome of sinonasal adenoid cystic carcinoma (snAdCC). We followed PRISMA guidelines and included studies reporting 5-year overall survival (OS) rates for snAdCC. Eligible studies were identified through a literature search and assessed using JBI critical appraisal checklist. A total of 17 studies were included comprising 2259 patients (mean age: 58.1 years, 52.7% female, 47.3% male). The meta-analysis demonstrated that the 5-year OS, 10-year OS, and 5-year disease-free survival (DFS) were 68%, 40%, and 47.2%, respectively. Descriptive statistics on study level showed high rates of locally advanced tumor stages at diagnosis: 23% cT3, 53% cT4, 3.4% N+, and 4.2% M+. 29.7% of the tumors were in the nasal cavity, 67.6% in the paranasal sinuses. The maxillary, ethmoid, sphenoid, and frontal sinus were affected in 50.9%, 7.2%, 4%, and 0.5%, of cases. A combination of surgery and radiotherapy was used in 45.4% of the patients and 19.3% of patients received surgery only. In conclusion, these findings emphasize the significance of thorough surveillance for individuals with snAdCC to identify any potential recurrence or progression of the disease.

Open rhinoplasty using a columellar strut: effects of the graft on nasal tip projection and rotation.

BACKGROUND: Despite the discordance in the literature concerning the effect of columellar strut grafts on nasal tip rotation, this method is often used when an increase in nasolabial angle or nasal tip projection is desired. OBJECTIVES: We aimed to elucidate the change in nasolabial angles and nasal tip projections after exclusive columellar strut graft implantations and in addition to other surgical steps. Furthermore, differences in these parameters between patients with conchal and septal columellar strut grafts were investigated. METHODS: A monocentric retrospective cohort study of 173 open septorhinoplasties with columellar strut graft technique, between 2006 and 2016, was conducted. The pre- and postoperative nasal tip projection, nasolabial and nasofrontal angle and interalar distance were determined and the Goode-ratio was calculated. RESULTS: In cases where uprotation was not specifically desired, neither nasolabial angles nor tip projections changed significantly, irrespective of whether a columellar strut graft was used alone or with additional surgical steps. If an uprotation through surgery was desired, a significant mean increase in nasolabial angle of 4.4° was achieved. Furthermore, conchal instead of septal columellar strut grafts showed significantly better results. CONCLUSION: In our study, a columellar strut graft-without any additional surgical step-does only have an improving impact on nasal tip rotations and projections, if specifically intended to by the surgeon. In other words, if the strut graft was not chosen for an uprotational intention, it did not relevantly impact on the nasolabial angle or nasal tip projection. However, in patients where an uprotation is desired, the columellar strut graft still represents a meaningful tool. Since conchal instead of septal columellar strut grafts showed better results, we suggest using them for these patients. LEVEL OF EVIDENCE: 2b.

Longstanding diplopia after ethmoidal artery ligation for epistaxis.

PURPOSE: In the rare case of intractable, posterior, non-sphenopalatine artery epistaxis, ligation of ethmoidal arteries using an external approach like a Lynch-type incision is required. Orbital complications, especially extra-ocular motility disorders with diplopia, are known, but in the literature rarely described. Our aim was to analyse the complication type, rate, and outcome of ethmoidal artery ligation for epistaxis. MATERIALS AND METHODS: Data between 2012 and 2017 of patients treated with ethmoidal artery ligation were analysed retrospectively and through a telephone interview using a non-standardized questionnaire. RESULTS: Data of 18 patients (m/f = 3/15) aged 53-83 years were reviewed. Epistaxis recurred in only one patient after 1 month. Five patients (28%) suffered from diplopia shortly after surgery. Motility analysis revealed full recovery with free motility in four out of five reported cases after 4-8 months, one patient still reports intermittent mild diplopia more than 1 year postoperatively. CONCLUSION: In patients with intractable, non-sphenopalatine artery epistaxis, anterior ethmoidal artery ligation was highly effective. Diplopia, however, occurred in one-third of our patient group. Information about motility restriction with longer standing diplopia are mandatory when consenting patients for ligation of ethmoidal arteries. Special care needs to be taken during dissection in the region of the trochlea and superior oblique muscle. LEVEL OF EVIDENCE: Case Series, level 4.

Trigeminal endonasal perception - an outcome predictor for septoplasty.

BACKGROUND: No adequate test exists to predict outcome after septoplasty. Despite adequate surgery, patients still might experience nasal breathing impairment. The aim of this study was to determine if pre-operative trigeminal sensitivity can predict satisfaction after septoplasty. METHODS: Single centre prospective cohort study in tertiary referral centre with follow-up time of 6 weeks postoperatively. Patients scheduled for septoplasty or septorhinoplasty with turbinoplasty were consecutively selected the day before surgery. Standard preoperative examinations (acoustic rhinometry and Sniffin’ Sticks 12 test), the evaluation of nasal obstruction on a visual analogue scale (VAS) and the trigeminal lateralisation task were performed before and 6 weeks after surgery. Biopsies were taken during surgery and TRPV1 mRNA expression was measured by PCR. RESULTS: Thirty patients were included with a median age of 29 years and equal gender distribution. Trigeminal perception and sensation of nasal obstruction showed a significant correlation: preoperative lateralisation test scores, representing endonasal trigeminal sensitivity, correlated significantly with the mean VAS change scores, which demonstrate subjective improvement. A lateralisation test score of 31.5 and more had a sensitivity of 88% to predict an improvement of more than 3 VAS points. Additionally, high TRPV1 mRNA expression was linked with good postoperative VAS scores. CONCLUSION: The preoperative evaluation of the trigeminal sensitivity could improve patients’ selection for septoplasty with a higher rate of satisfaction. Endonasal trigeminal sensitivity is directly linked with subjective outcome. Therefore, patients with low trigeminal sensitivity should undergo septoplasty only after thorough counselling.

Endotypes of chronic rhinosinusitis with nasal polyps with and without NSAID â€" intolerance.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2-dominated inflammatory disease of the upper air- ways. A subgroup of patients with CRSwNP suffer from intolerance to nonsteroidal anti-inflammatory drugs (NSAID) and develop NSAID-exacerbated respiratory disease (NERD). The aim of the study was to compare the cytokine based inflammatory endotype of nasal secretions of CRSwNP patients with and without NSAID intolerance. METHODS: Nasal secretions were collected from twenty-six patients suffering from CRSwNP, thirteen with NERD and thirteen without NSAID intolerance. As control, nasal secretions were collected from fifteen healthy donors. Tryptase and ten human cyto- kines were analyzed: interleukin (IL)-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, IL-17A, IL-23, IFN-g, and TNF-a by a cytokine multiple array on a Luminex 200 platform. RESULTS: Grade of polyposis and frequency of polyp surgery was more severe in NERD- compared to non-NERD patients. IL-6 and IL-5 in CRSwNP was significantly increased compared to healthy participants. IL-5 and IL-13 were significantly increased in subjects suffering from NERD compared to CRSwNP patients without NERD. CONCLUSION: We identified IL-13 as a possible specific biomarker in nasal secretions of patients with NERD, which allows us to differentiate between CRSwNP with vs. without NERD. The characterization of inflammatory endotypes in CRSwNP enables the introduction of the best available therapy in the context of precision medicine.

Prospective evaluation of a nonsurgical device for rhinoplasty.

BACKGROUND: Rhinoplasty represents one of the most challenging and frequently performed procedures in plastic surgery and non-surgical rhinoplasty is rarely considered. The aim of this study was to investigate whether the Nasella Nose Former (NNF), a newly developed non-surgical rhinoplasty device, could improve objective and subjective results following surgical rhinoplasty and even correct the shape of the nose without any surgery at all. METHODOLOGY: In this prospective, monocentric, two-armed, non-blinded randomized, controlled clinical trial, a total of 43 participants were included. In the Surgical group, 22 patients undergoing open or closed rhinoplasty with osteotomies were randomised based on their birth year; 15 of them got to wear the NNF over 8 weeks postoperatively and 7 patients getting surgery without the NNF formed the control group. In the Cosmetic group, 21 participants wore the NNF without surgery over 14 months. At every follow-up exam, angles for crookedness, nasal hump and width were measured, the investigator assessed the patients nose and asked for patient satisfaction using a Likert-scale. RESULTS: Patients in the Surgical group wearing the NNF did not show any significant difference concerning objective measurements, investigator assessments and patient satisfaction compared to those not wearing the NNF. In the Cosmetic group, participants did not show objective improvements in measurements and investigator assessment. However, participants were significantly more satisfied after 14 months with their nasal back, nasal axis and outer nose in general. CONCLUSIONS: Considering the results of this study, we conclude that this perfectly customised external device to enhance surgical rhinoplasty outcomes or correct the shape of the nose without surgery does not seem to be effective and that further investigations in this field are not meaningful.

Occurrence of occult CSF leaks during standard FESS procedures.

OBJECTIVE: To determine the incidence of occult cerebrospinal fluid leaks (CSF) after functional endoscopic sinus surgery (FESS) and to evaluate the diagnostic performance of beta2-transferrin in blood-contaminated conditions. STUDY DESIGN: Prospective cohort study. METHODS: An analysis of 57 intraoperative samples using hydrogel 6 beta2-transferrin assay after FESS was undertaken. In case of CSF positive samples and continuing rhinorrhea, reanalysis after more than 1 year was conducted. In-vivo analysis of a primary spontaneous CSF leak sample took place to verify difficulties in detecting beta2-transferrin in blood-contaminated settings. Own titrations were performed to evaluate detection limits of CSF by beta2-transferrin and beta-trace protein assays in these settings. RESULTS: An incidence of 13% for occult CSF leaks after FESS was found. In blood-contaminated conditions, routine beta2-transferrin assays showed low sensitivity. In over 1 year follow-up, all samples were negative for CSF and none of them developed clinical relevant CSF leaks or meningitis. CONCLUSION: Occult and clinically irrelevant CSF leaks do occur in a significant proportion of patients during and shortly after FESS. Intra- and postoperatively, routine beta2-transferrin assays show low sensitivity. They should not be used in these settings. The clinical course of patients with occult CSF leaks indicated possibility of an uneventful follow-up.

What is the influence of tonsillectomy on the level of periodontal pathogens on the tongue dorsum and in periodontal pockets.

BACKGROUND: For periodontal treatment, the full mouth disinfection approach suggests disinfection of oral soft tissues, such as tongue and tonsils concomitant to scaling and root planning since patients might benefit from treatment of these oral niches either. Periodontopathogenes in tonsillar tissue support this hypothesis. This prospective controlled clinical study investigated the change in the oral flora of patients who underwent tonsillectomy. Pockets were tested for eleven bacterial species before and six weeks after the surgical intervention. METHODS: Fifty generally healthy adults were included in this study. The test group consisted of 25 patients with tonsillectomy. The control group included 25 patients with otorhinolarynologic surgery without involvement of the oral cavity. Clinical parameters such as probing pocket depth, bleeding-on-probing index and plaque index were registered the evening before surgery. Also bacterial samples from the gingival sulcus and dorsum linguae were taken, and an additional sample from the removed tonsils in the test group. Six weeks after the intervention microbial samples of pockets and tongue were taken again. Data were tested for significant differences using Wilcoxon rank and Whitney-u-test. RESULTS: No relevant intra- or intergroup differences were found for the change of the eleven investigated species. CONCLUSION: Based on the results of the present study, tonsillectomy does not seem to have an immediate relevant effect on the bacterial flora of tongue or periodontium. This study design was approved by the ethical committee of Zurich (KEK-ZH-Nr.2013-0419). TRIAL REGISTRATION: The trial was retrospectively registered in the German Clinical Trials Register ( DRK00014077 ) on February 20, 2018.

[Cannabis-induced disorders]. / Cannabisinduzierte Störungen.

Use and misuse of cannabis and marihuana are frequent. About 5% of the adult population are current users but only 1.2% are dependent. The medical use of cannabis is controversial but there is some evidence for improvement of chronic pain and spasticity. The somatic toxicity of cannabis is well proven but limited and psychiatric disorders induced by cannabis are of more relevance, e.g. cognitive disorders, amotivational syndrome, psychoses and delusional disorders as well as physical and psychological dependence. The withdrawal symptoms are usually mild and do not require pharmacological interventions. To date there is no established pharmacotherapy for relapse prevention. Psychosocial interventions include psychoeducation, behavioral therapy and motivational enhancement. The CANDIS protocol is the best established German intervention among abstinence-oriented therapies.

Comparing Nalmefene and Naltrexone in Alcohol Dependence: Are there any Differences? Results from an Indirect Meta-Analysis.

BACKGROUND: The mu-opioid antagonist naltrexone is one of the few approved pharmacotherapies for the treatment of alcohol dependence. Recently, the mu-opioid antagonist and partial kappa agonist nalmefene was approved by the European Medicines Agency for the reduction of alcohol consumption in adult patients with alcohol dependence. To date, no head-to-head studies have compared the efficacy and safety of naltrexone and nalmefene in reducing alcohol consumption. METHODS: An indirect meta-analysis of randomized controlled studies on these 2 medications was conducted. A random effects model was used to measure effects and compare the 2 medications. 4 placebo-controlled studies with nalmefene and 13 with naltrexone were included. RESULTS: A statistically significant advantage of nalmefene towards naltrexone in the 2 patient-relevant outcome efficacy criteria, quantity and frequency of drinking, was found. Both drugs had a benign safety profile. CONCLUSIONS: This indirect meta-analysis indicates an advantage of nalmefene over naltrexone. Nalmefene is an effective and well-tolerated medication for the reduction of alcohol consumption. Additional data are necessary to demonstrate possible advantages of nalmefene over naltrexone in the treatment of alcohol dependence.

Current Findings and Mechanisms of Action of Disulfiram in the Treatment of Alcohol Dependence.

As an alcohol-aversive agent, disulfiram occupies an exceptional position in the pharmacological relapse prevention of alcohol dependence. In contrast to anti-craving drugs, disulfiram does not modulate neurobiological mechanisms of addiction, but rather works by producing an aversive reaction when combined with alcohol. Therapeutic and adverse effects are therefore closely related: On the one hand, the aversiveness of the disulfiram ethanol reaction has the potential to support abstinence in a subgroup of alcohol-dependent patients, while on the other hand it becomes a health threat if the patient fails to maintain complete abstinence. The exceptional position of disulfiram is also related to the role that expectations play in the mediation of therapeutic effects. These are not determined by the pharmacological effects or the actual occurrence of a disulfiram-ethanol reaction, but are attributable to patient awareness that the drug was consumed and the corresponding anticipation of an aversive reaction if combined with alcohol. This is in line with the findings of a recent meta-analysis that only showed significant effects for disulfiram in open-label trials. The authors of the meta-analysis conclude that due to expectations induced in both the treatment and placebo groups, blinded studies are incapable of distinguishing a difference between groups. The mediation of therapeutic effects through expectation has a number of consequences for clinical practice and future research on disulfiram.

[Emotion regulation and quality of life in consumption of cocaine and amphetamines : Results of an online survey]. / Emotionsregulation und Lebensqualität bei Amphetamin- und Kokainkonsum : Ergebnisse einer Online-Studie.

BACKGROUND: The online study presented surveyed occasional users, high-risk users and non-consumers of psychotropic substances for relationships between consumer type and emotion regulation (ER), health-related quality of life (HRQOL) and coping strategies. METHODS: A total of 199 people participated in the survey. The sample was split into three groups depending on a substance list and a detailed questionnaire regarding the consumption habits: 28 individuals had no illicit drug experience, 127 were occasional users and 44 frequent (high-risk) users. The sample set was tested using the (1) emotion regulation inventory, (2) the coping inventory for stressful situations and (3) the medical outcomes study (MOS) 36-item short-form health survey. RESULTS: Regarding ER the occasional users showed no significant differences to the two reference groups, except for the scale of re-evaluation where the high-risk consumers scored higher than the occasional users. Regarding HRQOL no significant differences were observed between the three groups; however, significant differences were observed between persons with strong and weak physical and mental HRQOL scores and satisfaction with own emotion regulation. The search for predictors showed a significant predictive value for gender, the number of inhabitants at the place of residence and the ER strategy of re-evaluation in negative emotions for the allocation to a consumer type. Neither substance consumption as an ER strategy nor a relationship between consumer type and coping strategy and/or HRQOL could be observed. DISCUSSION: With respect to ER the only significant difference observed was that of high-risk users employing the strategy of re-evaluation more often than occasional users. A possible explanation is reality embellishment and a down-playing function of this strategy associated with drug consumption. Therefore, the assumed relationship between affective dysfunction and drug addiction could not be observed.

[Guideline-oriented treatment of alcohol-related disorders]. / Leitlinienorientierte Behandlung alkoholbezogener Störungen.

Alcohol use disorders (e.g. abuse and dependence) account for a plethora of consequences for affected individuals and for a substantial proportion of the overall burden of disease for the community. To date, existing treatment options are either poorly known by doctors or they are not fully applied and only approximately 15% of potential patients are treated with a mean latent period of 10 years between early symptoms and the first intervention. So-called S3 treatment guidelines were recently developed to close this gap. Representatives of more than 50 learned societies, families and patients were involved. A systematic literature search from 2005 to 2012 was performed and more than 120 recommendations were made. Financing came exclusively from those societies and the academic and treatment institutes involved.This article summarizes the recommendations pertinent for psychiatrists and include early detection and intervention, acute withdrawal and long-term psychotherapy and pharmacotherapy. Classical and new treatment goals are discussed. If the new guidelines were properly applied an increase in patients receiving treatment to 30-40% could be expected, which would improve the quality of lives of affected persons and their families and in Germany would save several thousand lives per year.

No evidence for development of tolerance after repeated use of propofol for electroconvulsive therapy.

INTRODUCTION: The short-acting narcotic propofol is used for sedation during electroconvulsive therapy (ECT). It remains unclear whether patients develop tolerance to propofol after repeated administration. Therefore, we studied whether propofol dosage had to be increased during a course of ECT. METHODS: This retrospective study evaluated records of 39 in- and outpatients at a Swiss psychiatric hospital who underwent 10-21 ECT sessions for affective disorder over 4-28 weeks in 2011-2013. We examined the dose of propofol required to achieve deep sedation at the first and last ECT sessions. RESULTS: 13/39 patients (33.3%) needed a slightly higher propofol dose at the last ECT session than at the first (Group 1), 12 patients (30.8%) needed the same dose at the first and last sessions (Group 2) and 14 patients (35.9%) needed a lower final dose (Group 3). CONCLUSIONS: In our study patients did not appear to develop tolerance to propofol after repeated administration. Although the lack of a systematic dosing scheme in our study limits the conclusions that can be drawn, recent studies in animal models indicate that tolerance development is rather unlikely with propofol. Further studies are required to clarify the question of whether repeated use of propofol leads to tolerance.

Recent Developments in Pharmacotherapy of Alcoholism.

INTRODUCTION: Alcohol use disorders are common, but only a small minority of patients receive adequate treatment. Cognitive-behavioural therapies, motivational enhancement interviewing and brief interventions are established treatments, but few pharmacotherapies are available. AREAS COVERED: This narrative focuses on the neurobiological basis of alcohol use disorders and on emerging drugs that either have recently been approved or look likely to find their way into clinical practice. To date, acamprosate and the opioid antagonist naltrexone have been approved for treatment of alcohol dependence. Recently, the mu-opioid antagonist and partial kappa agonist nalmefene was approved by the European Medicines Agency for reduction of alcohol consumption. Novel clinical approaches include drugs established for other indications such as the GABA-B receptor agonist baclofen, anticonvulsants such as topiramate and gabapentin, the partial nicotine receptor agonist varenicline, and other drugs. Developments in pharmacogenetics are discussed. CONCLUSIONS: The development of pharmaceutical agents to treat alcohol use disorders has lagged behind that of depression and schizophrenic psychosis and is hampered by an incomplete understanding of the neurobiological background. Pharmacogenetics may improve treatment in the future.

Multilocular sinonasal malignant melanoma: a poor prognostic subgroup?

Clinical observations show that two subtypes of sinonasal malignant melanoma exist: uni- and multilocular melanoma. The aim of this retrospective study was to determine the prevalence and outcome of multilocular sinonasal malignant melanoma. All patients with sinonasal malignant melanoma treated at our institution between 1992 and 2011 were included. Survival and recurrence data were analyzed related to the distribution pattern of the tumors and other factors. Twenty-five patients were identified and included in the analysis. Seven patients (28 %) suffered from multilocular, the remaining 18 patients (72 %) from unilocular sinonasal malignant melanoma. The first group showed a significantly worse disease-free survival, whereas disease-specific and overall survival did not differ between the two subtypes. Multilocular sinonasal malignant melanoma is associated with an unfavorable disease-free survival compared to its unilocular counterpart.

[Pharmacological cognitive enhancement from a perspective of misuse and addiction]. / Pharmakologisches Neuroenhancement aus Sicht der Suchtmedizin.

Pharmacological "cognitive enhancement" (CE) and "pharmacological neuroenhancement" (PN) are different terms to describe the use of diverse substances by healthy individuals aiming at an increase of individual cognitive skills. Targets of CE are an increase of vigilance, attention, concentration, memory and motivation. Substances used for pharmacological CE can be divided into two categories: stimulants and non-stimulants. The sub-group of methylxanthines like caffeine as well as the sub-group of amphetamines like prescription and illicit amphetamine as well as methylphenidate and modafinil belongs to the group of stimulants; antidementives, antidepressants, phytopharmaceutical products like Ginkgo biloba etc. belong to the group of non-stimulants. Prevalence rates depend on the (type of) study and (group of) substances used for CE. And they range from a 1 % lifetime prevalence rate up to 20 % one-year prevalence rate. This review presents stimulant and non-stimulant substances, their limited clinical effects on cognitive skills as well as their prevalence rates and the aspect of misuse and addiction of the above-mentioned substances which belongs to their respective category.