Development and External Validation of a Model to Predict Overall Survival in Patients With Resected Gallbladder Cancer.

OBJECTIVE: The aim of this study was to develop and validate a clinical prediction model to predict overall survival in patients with nonmetastatic, resected gallbladder cancer (GBC). BACKGROUND: Although several tools are available, no optimal method has been identified to assess survival in patients with resected GBC. METHODS: Data from a Dutch, nation-wide cohort of patients with resected GBC was used to develop a prediction model for overall survival. The model was internally validated and a cohort of Australian GBC patients who underwent resection was used for external validation. The performance of the American Joint Committee on Cancer (AJCC) staging system and the present model were compared. RESULTS: In total, 446 patients were included; 380 patients in the development cohort and 66 patients in the validation cohort. In the development cohort median survival was 22 months (median follow-up 75 months). Age, T/N classification, resection margin, differentiation grade, and vascular invasion were independent predictors of survival. The externally validated C-index was 0.75 (95%CI: 0.69-0.80), implying good discriminatory capacity. The discriminative ability of the present model after internal validation was superior to the ability of the AJCC staging system (Harrell C-index 0.71, [95%CI: 0.69-0.72) vs. 0.59 (95% CI: 0.57-0.60)]. CONCLUSION: The proposed model for the prediction of overall survival in patients with resected GBC demonstrates good discriminatory capacity, reasonable calibration and outperforms the authoritative AJCC staging system. This model can be a useful tool for physicians and patients to obtain information about survival after resection and is available from https:// gallbladderresearch.shinyapps.io/Predict_GBC_survival/.

Association between olfactory function and quality of life in patients with olfactory disorders: a multicenter study in over 760 participants.

BACKGROUND: This cross-sectional, multi-centric study aimed to investigate the differences in quality of life among patients with olfactory dysfunction (OD) of different origin, and to identify factors associated with olfactory-related quality of life (QOL). METHODS: Seven hundred sixty-three adults were recruited from 8 Smell & Taste clinics in Germany, Switzerland, and Austria. Olfactory-related QOL was assessed by the Questionnaire of Olfactory Disorders (QOD). Olfactory function was assessed with the "Sniffin' Sticks" test; self-assessment was performed with visual analog scales. RESULTS: Patients with post-infectious and post-traumatic OD showed poorer olfactory-related QOL than patients with sinonasal and idiopathic OD. The olfactory-related QOL was positively associated with the "Sniffin' Sticks" test score, self-assessed olfactory function, disease duration, and age, with younger olfactory dysfunction patients showing lower QOL. Female patients presented with poorer olfactory-related QOL. In addition, the results showed that self-assessment of olfactory function explained more of the variance in olfactory-related QOL than olfactory function evaluated by the Sniffin’ Sticks test. CONCLUSIONS: In addition to the psychophysical testing results, several factors such as disease cause, disease duration, sex, or self- assessed olfactory dysfunction should be taken into account when assessing the individual severity of the smell loss.

Experimental Measurement of the Static Coefficient of Friction at the Ti-Ti Taper Connection in Total Hip Arthroplasty.

The modular taper junction in total hip replacements has been implicated as a possible source of wear. The finite-element (FE) method can be used to study the wear potential at the taper junction. For such simulations it is important to implement representative contact parameters, in order to achieve accurate results. One of the main parameters in FE simulations is the coefficient of friction. However, in current literature, there is quite a wide spread in coefficient of friction values (0.15 - 0.8), which has a significant effect on the outcome of the FE simulations. Therefore, to obtain more accurate results, one should use a coefficient of friction that is determined for the specific material couple being analyzed. In this study, the static coefficient of friction was determined for two types of titanium-on-titanium stem-adaptor couples, using actual cut-outs of the final implants, to ensure that the coefficient of friction was determined consistently for the actual implant material and surface finish characteristics. Two types of tapers were examined, Biomet type-1 and 12/14, where type-1 has a polished surface finish and the 12/14 is a microgrooved system. We found static coefficients of friction of 0.19 and 0.29 for the 12/14 and type-1 stem-adaptor couples, respectively.

[Chemosensory Evoked Changes of Breathing Pattern During Propofol-induced Sedation]. / Chemosensorisch evozierte Atemänderungen während zweier Propofol-induzierter Sedierungsstadien.

BACKGROUND: The affective valence of an olfactory stimulus will be encoded in its respiratory response. Unpleasant odors shorten the inhalation of the first stimulated breaths in wakefulness and sleep. The aim of the present study was to assess the effekt of intravenous anesthetic propofol on the chemosensory evoked changes of breathing pattern. MATERIAL AND METHODS: 13 ASA 1/2 patients got intranasal chemosensory stimuli (H2S and CO2) by flow-olfactometer during "deep" (EEG-based bispectral analysis, BIS:≤60) and "moderate" (BIS>60) propofol-induced sedation with preserved spontaneous breathing. The duration of the in- and exhalation was analyzed for 5 breaths before and for 2 breaths after the onset of stimulation. RESULTS: During deep sedation respiratory reactions were observed only by CO2 irritation. During moderate sedation respiratory responses were evoked by H2S stimuli, too. In moderate sedation extensions of the inhalations of the first breath after both the unpleasant pure olfactory H2S stimuli and the trigeminal stimuli were more frequent than reductions. CONCLUSION: Olfactory stimuli change the breathing only during moderate sedation, trigeminal stimuli during deep and moderate propofol-induced sedation. In opposite to both wakefulness and sleep the duration of inhalation is often extended by H2S-stimuli during moderate sedation.

Population-based analysis of tonsil surgery and postoperative hemorrhage.

Although tonsil surgery is one of the most frequent otorhinolaryngological procedures, not many population-based regional or country-wide studies are published on the incidence of postoperative bleeding and its risk factors. 2,216 patients underwent tonsil surgery in 2012 in Thuringia, a federal state in Germany. Most frequent indications were recurrent tonsillitis (44 % of all cases), tonsillar abscess (27 %), and tonsillar hyperplasia (20 %). 29 % of the patients were <10 years of age. Most frequent methods of surgery were tonsillectomy (73 %) and tonsillotomy (19 %). 215 patients (10 %) had 221 events of a postoperative hemorrhage. Re-surgery for hemostasis was necessary in 137 patients (6 %). The interval to re-surgery was 4.4 ± 4.6 days. The re-surgery rate was 8, 0.2, and 15 % after tonsillectomy, tonsillotomy, and radical tonsillectomy, respectively. In cases of recurrent tonsillitis, male gender (p < 0.001), age >24.78 years (median; (p = 0.018), and waiving of perioperative antibiotics (p = 0.029) were independent factors associated with hemorrhage. In cases of tonsillar hyperplasia tonsillectomy instead of tonsillotomy, the only significant risk factor was postoperative hemorrhage (p = 0.005). The overall incidence of tonsillar surgery was 87.6/100,000. The highest incidence was seen for patients 3-4 years of age with 862.7/100,000. In children <10 years, the incidence was always higher for boys than for girls. Throughout all age groups, a reverse gender relation was only seen, if surgery was indicated for recurrent tonsillitis. We recommend establishing national guidelines for indication of tonsil surgery, especially of tonsillectomy, including recommendations for perioperative care to decrease variations in tonsil surgery rates and minimize postoperative complications.

[Global and Spatial Gustatory Function after Proven Unilateral Transsection of the Chorda Tympani]. / Globales und regionales Schmeckvermögen nach einseitiger Durchtrennung der Chorda tympani.

BACKGROUND: A transection of the chorda tympani results in loss of spatial gustatory function on the ipsilateral tongue. Most patients do not notice anymore this alteration. The cause is unclear. Do adjacent gustatory areas become more sensitive or is the gustatory perception rather independent of the size of stimulated area? METHODS: 51 patients with proven unilateral transection of the chorda tympani and 51 healthy subjects were tested for gustatory recognition thresholds. The methods used were the "three-drops-choice-technique" by Henkin to evaluate the whole mouth taste (global taste examination) and the "spatial taste test" to evaluate the local gustatory function on 4 areas of the tongue. The taste solutions were sweet, sour, salty and bitter with increasing concentrations. RESULTS: The global gustatory function of the patients and of the control group did not differ in either the 4 taste qualities but the composite score was increased within the group of patients. Most patients did not realize that. The spatial taste examination showed reduction of taste perception on 3 of the 4 gustatory areas of the tongue in the patients. The decreased gustatory function on the area of the transected chorda remained unchanged over time. The taste attenuation on the ipsilateral back area and the contralateral front area improved over time. CONCLUSION: Transection of chorda tympani also leads to an attenuation of spatial gustatory function in adjacent areas. Therefore, adjacent areas cannot be taken as reference. Instead, taste function has to be compared to the results of healthy probands.

[Sleep-related breathing disorders and (resulting) cardiovascular diseases]. / Schlafbezogene Atmungsstörungen und kardiovaskuläre (Folge-)Erkrankungen.

Sleep-related breathing disorders occur in cardiology patients mostly as obstructive or central sleep apnea with Cheyne-Stokes respiration. The prevalence and incidence are clearly increased in comparison to the general population. Depending on the underlying cardiac disease up to 75% of patients can have obstructive or central sleep apnea and up to 50% have indications for therapy according to the current guidelines. Obstructive sleep apnea is considered to be an independent and well treatable risk factor for the development and deterioration of many cardiovascular diseases. This review briefly describes examples of prevalence, pathophysiology and current study situation with respect to the association between sleep-related breathing disorders and arterial hypertension, atrial fibrillation, arteriosclerosis with coronary heart disease, myocardial infarction and heart failure. Although the role of obstructive sleep apnea as a risk factor for the development of these diseases is well documented, central sleep apnea is less of a risk factor per se but is considered to mirror an underlying cardiac disease with then further negative consequences for this disease. It is not the sleep apnea per se but the subsequent cardiovascular diseases which limit the prognosis of these patients and therefore bring them into the focus of cardiology. Obstructive and central sleep apnea can be successfully and sustainably treated by various forms of nocturnal positive airway pressure therapy. Furthermore, there are several therapeutic procedures which are currently being tested and the significance will be investigated in the coming years.

Olfactory training for patients with olfactory loss after upper respiratory tract infections.

Olfactory training consisting of daily suprathreshold odor exposure over 12 weeks seems to improve olfactory function. It is unknown if a longer period of training might be more effective. A prospective non-randomized clinical study was performed including 39 patients with olfactory loss after an upper respiratory tract infection (URTI) of less than 24 months duration. Patients exposed themselves with suprathreshold concentrations of four odors (rose, eucalyptus, lemon, cloves) applied in ''Sniffin' Sticks'' felt-tip pens over 32 weeks. Olfactory function was performed before (T1), after 16 weeks (T2), and 32 weeks of training (T3) using the 'the Sniffin' Sticks test kit calculating the TDI score (Threshold, Discrimination, Identification). The mean TDI score showed a non-significant trend of improvement at T2, and was significantly increased at T3 (p = 0.021). Overall, 31 patients (79%) showed an increased TDI score at T3. The increase of TDI from T1 to T3 was 4.6 ± 5.1. Age, gender, duration and initial severity of olfactory loss had no influence on the improvement (all p > 0.05). Only patients with a D score lower than the median value of 8 showed a significantly higher increase of the D score at T3 (p = 0.004). The present study confirmed that olfactory training improves olfactory function in patients with olfactory loss after URTI. A longer duration of training over 32 weeks seems to increase the effectiveness in comparison to a 12-week period. This was tested in a completed German multicenter trial to be published soon containing a control group to include the effect of a spontaneous recovery after URTI.

[The regularity of the breathing pattern of both sitting and reclining adults is not different]. / Die Regelmäßigkeit der Ruheatmung sitzender und liegender Erwachsener unterscheidet sich nicht.

BACKGROUND: A prestimulatory regular breathing is required for the respiration-olfactometry. In a sitting position, just about every second prestimulatory breathing sequence fulfilled this requirement checking off -line. It should be examined whether breathing in reclining position is more regular. METHODS: The coefficients of variation of the time parameters of breathing in reclining and sitting position during 30 min were determined and compared. RESULTS: Breathing regularity did not increase in reclining position with 48 healthy persons (age group 1: 18 to 30 years, n = 24, 18 women; age group 2: > 55 years, n = 24, 13 women). The age and gender had no eff ect on the proportion of regular breathing. With 7 persons, the yield of 5 on each other following regular breaths was inadequate. Additionally one person excluded from our study was not able to breathe regularly without interruptions. CONCLUSION: The respiration-olfactometry cannot be performed in each person. It is not more successful in reclining than in sitting position.

Parotidectomy and submandibulectomy for benign diseases in Thuringia, Germany: a population-based study on epidemiology and outcome.

Although salivary gland surgery for benign diseases is an integral part of clinical routine of head and neck surgeons, there is not many population-based data published on incidence and efficiency of this surgery. Parotidectomy was performed in 180 patients and submandibulectomy in 97 patients for benign diseases in eight otorhinolaryngology and two maxillofacial surgery departments in Thuringia, Germany, in 2005. All patients were analysed regarding patients' characteristics, therapy, complications and further course of disease. Predominant indications were epithelial tumours for parotidectomy (79 %) and sialolithiasis for submandibulectomy (50 %). The most frequent tumour types were pleomorphic adenoma (46 %) and Warthin tumours (29 %). Pleomorphic adenoma was significantly more frequent in female patients and Warthin tumours in male patients and smokers. The incidence of parotidectomy, i.e. the surgical rate, was 7.8/100,000 habitants and of submandibulectomy 4.1/100,000 habitants. One hundred and seventy-eight tumours including 154 epithelial tumours resulted in an incidence of 7.6/100,000 habitants for all treated tumours and of 6.6/100,000 for epithelial tumours, respectively. The majority of parotid cases were treated by lateral parotidectomy (79 %). Relevant complications were observed in 22 % of patients. After parotidectomy and submandibulectomy a postoperative facial palsy was observed in 28 and 2 % of cases, respectively. Only 1 % was permanent. During a mean follow-up time of 9.6 months, 3 % of parotidectomy patients developed a Frey's syndrome needing treatment and 0.8 % developed a tumour recurrence. This population-based analysis shows that salivary gland surgery is performed in higher incidence than expected, effectively and with low-risk in daily routine of head and neck surgeons.

[Ability of smelling is reduced reversibly by acute smoking and permanently by chronic smoking]. / Riechsinn wird durch akutes Rauchen reversibel und durch chronisches Rauchen dauerhaft geschädigt.

BACKGROUND: Whether smoking affects the sense of smell is in debate. To exclude a bias by presbyosmia, we analyzed the influence of acute and chronic smoking on the ability to smell in young adults. MATERIAL AND METHODS: 40 smokers (23 women, 17 men) aged between 18-34 years were included. They smoked in average 19.6 cigarettes per day and had an average of 7.96 pack years (minimum: 2.5; maximum: 25). The sense of smell was evaluated using the Sniffin' sticks© olfactory test-battery in 215 min 5 times. The impact of a 2 h controlled abstinence time and subsequent smoking of a cigarette were measured. 43 never smokers were tested as control group. RESULTS: Smoking had a 2-fold impact on the sense of smell: there was a reversible impairment after acute smoking and a permanent reduction of olfaction in relation to the pack years. In summary, the young smokers remained normosmic, although they showed significantly worse test results compared to the group of never smokers. The olfactory capacity of different groups of smokers differed up to maximum of 4.5 TDI points (sum of olfactory threshold-, discrimination- and identification-score). CONCLUSIONS: The damage caused by smoking seems to be settled in the border area between norm- and hyposmia. In case of an expert opinion the patient should be asked for the pack years and should keep 2 h controlled smoking abstinence prior to olfactory testing.

[Health services research on paranasal sinus surgery in Thuringia: epidemiologic key data and outcome]. / Versorgungsforschung zu Nasennebenhöhlenoperationen in Thüringen: Epidemiologie und Ergebnisse.

BACKGROUND: Although modern minimal-invasive paranasal sinus surgery is an integral part of clinical routine of otorhinolaryngologic surgeons, there are no population-based data on incidence and efficiency of this surgery published. MATERIAL AND METHODS: 1,582 patients underwent paranasal sinus surgery in the 8 Thuringian departments of otorhinolaryngology in 2005. All patients were analysed regarding patients' characteristics, therapy, complications and further course of disease. RESULTS: The incidence of paranasal sinus surgery was 46/100,000 for women and higher for men with 72/100,000. Median age was 48 years. Chronic sinusitis was the main reason for surgery (94%; including 33% with nasal polyps) and was performed dominantly as endoscopic sinus surgery (96%). Surgery was performed bilaterally in 75% of the cases and as primary surgery. In most cases at least 2 paranasal sinuses per side were approached. Relevant complications were observed in 4% of patients. During the follow-up time of 45-51 months a recurrence was observed in 9% of cases. Using a multivariate regression analysis, revision surgery, allergic subject and diagnosis of a malignant tumor were significant independent risk factors to predict a recurrence. Older age and longer time of surgery were significant independent risk factors for a complication. CONCLUSION: This population based analysis is showing that modern paranasal sinus surgery is performed in high incidence, effectively and with low-risk on a large scale in daily routine of rhinologic surgeons.

Differences in anosmic and normosmic group in bimodal odorant perception: a functional- MRI study.

So-called bimodal odorants are able to stimulate the intranasal trigeminal system at relatively low concentrations. Using them as stimuli, the current study focused on the interaction between the olfactory and trigeminal systems at a cerebral level. In the experiment, menthol was used at two concentrations, low and high, and these were delivered to two groups of subjects, a healthy control group and an anosmic group who were unable to perceive smells. A computer-controlled olfactometer based on principles of air-dilution was used to deliver the stimuli, while the brain functions were assessed by a functional magnetic resonance imaging (fMRI) technique. SPM5 was used for data analysis. The results showed that normosmic subjects exhibited activation in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), prefrontal cortex (PFC), and cerebellum. Whilst anosmic subjects activated the same area inside the anterior cingulate; moreover a cluster of activation was found in the left parahippocampal gyrus. In controls, an effect of stimulus intensity was localized between the anterior cingulated, the medial frontal gyrus and the cerebellum; such areas could not be found in anosmic subjects. These results suggest that the olfactory system modifies trigeminally mediated information causing an evident effect in the differentiation between stimulus intensities.

[Volume alterations in the gray matter of anosmic subjects. Lessons we can learn from voxel-based morphometry]. / Volumenänderungen der grauen Hirnsubstanz bei Anosmikern. Erkenntnisse durch voxelbasierte Morphometrie.

Alterations in the central nervous system in patients with a loss of sense of smell are well documented for the olfactory bulb (OB). Here we present a voxel-based morphometry (VBM) study on cerebral alterations in the gray matter of patients with anosmia above the OB. 3-Tesla MRI datasets were obtained from 17 patients with anosmia as well as from 17 normosmic controls. Data processing and evaluation was performed using the SPM5 software package (Wellcome Department of Imaging Neuroscience Group, London, UK) and the implemented VBM5 toolbox. Patients with anosmia showed a significant volume decrease in the gray matter in the primary olfactory cortex as well as in secondary olfactory areas (insular cortex, orbitofrontal cortex, cingulate cortex and hippocampus). Furthermore, volume decreases in areas like the nucleus accumbens with adjacent subcallosal gyrus and the dorsolateral prefrontal cortex were found. Longer disease duration was associated with more profound alterations in the gray matter. VBM is appropriate to document brain alterations in patients with olfactory disorders.

[Progressive hoarseness]. / Progressive Heiserkeit.

A 31-year-old female teacher presented with a 6-month history of progressive hoarseness. The rigid laryngeal endoscopy showed corresponding transversal cream-yellow nodular lesions in the submucosal space of the middle third of both vocal folds. These are characteristic for bamboo nodes which are rare and strongly associated with autoimmune disease. In the present case a hitherto undiscovered Sjögren syndrome was diagnosed. After surgical excision, local steroid therapy and voice training a considerable voice improvement could be achieved.

[Detection of olfactory areas in functional MRI--how many repetitions are necessary?]. / Darstellung olfaktorischer Areale mittels funktionellem MRT--wieviele Reize sind notwendig?

BACKGROUND AND PURPOSE: A useful tool for the investigation of the human olfactory system is functional magnetic resonance tomography (fMRI). Since the length of the fMRI examination is a limiting factor for its usefulness in clinical routine in this study a fast, reliable paradigm should be found in order to reduce the overall examination time and the olfactory habituation. METHODS: A MRI-compatible constant flow olfactometer was developed. 9 healthy normosmic subjects were stimulated 16 times with the odorant phenyl-ethyl-alcohol (PEA) using an event-related design. The statistical evaluation of the data was performed by the MATLAB based SPM5 software package. RESULTS: The group analysis showed cerebral activations within the insula, the adjacent operculum and orbitofrontal cortex bilaterally. Furthermore, bilateral activations were measured in the cingulum, piriform cortex and the cerebellum. All mentioned areas could be already identified after 8 repetitions of odorant condition. Bilateral insular activations and activations in the left piriform cortex were even shown after 4 repetitions. In the single subject analysis, all 9 subjects exhibited insular activity and in 3 subjects showed activation of the piriform cortex after 4 repetitions. CONCLUSION: In olfactory fMRI, stimulus repetition more than 8 did not improve the quality and reliability of the results. Therefore, 4-8 stimuli are expected to be sufficient.