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.

Identifying Biomarkers in Lymph Node Metastases of Esophageal Adenocarcinoma for Tumor-Targeted Imaging.

INTRODUCTION: Tumor-targeted imaging is a promising technique for the detection of lymph node metastases (LNM) and primary tumors. It remains unclear which biomarker is the most suitable target to distinguish malignant from healthy tissue in esophageal adenocarcinoma (EAC). OBJECTIVE: We performed an immunohistochemistry study to identify viable tumor markers for tumor-targeted imaging of EAC. METHODS: We used samples from 72 patients with EAC to determine the immunohistochemical expression of ten potential tumor biomarkers for EAC (carbonic anhydrase IX [CA-IX], carcinoembryonic antigen [CEA], hepatic growth factor receptor, epidermal growth factor receptor, epithelial membrane antigen [EMA], epithelial cell adhesion molecule [EpCAM], human epidermal growth factor receptor 2 [HER-2], urokinase plasminogen activator receptor, vascular endothelial growth factor-A [VEGF-A], and VEGF receptor 2). Immunohistochemistry was performed on tissue microarrays of LNM (n = 48), primary EACs (n = 62), fibrotic tissues (n = 11), nonmalignant lymph nodes (n = 24), and normal esophageal and gastric tissues (n = 40). Tumor marker staining was scored on intensity and percentage of positive cells. RESULTS: EMA and EpCAM showed strong expression in LNM (> 95%) and primary EACs (> 95%). Significant expression was also observed for LNM and EAC using VEGF-A (85 and 92%), CEA (68 and 54%), and CA-IX (4 and 34%). The other tumor biomarkers showed expression of 0-15% for LNM and primary EAC. Except for VEGF-A, nonmalignant lymph node staining was scored as slight or absent. CONCLUSIONS: High expression rates and correlation between LNM in EAC combined with low expression rates in healthy lymph nodes and esophagus tissues were observed for EpCAM and CEA, meaning these are promising targets for tumor-targeted imaging approaches for lymph nodes in patients with EAC.

The diagnostic accuracy of CT and MRI for the detection of lymph node metastases in gallbladder cancer: A systematic review and meta-analysis.

BACKGROUND: Lymph node metastases (LNM) are an ominous prognostic factor in gallbladder cancer (GBC) and, when present, should preclude surgery. However, uncertainty remains regarding the optimal imaging modality for pre-operative detection of LNM and international guidelines vary in their recommendations. The purpose of this study was to systematically review the diagnostic accuracy of computed tomography (CT) versus magnetic resonance imaging (MRI) in the detection of LNM of GBC. METHODS: A literature search of studies published until November 2017 concerning the diagnostic accuracy of CT or MRI regarding the detection of LNM in GBC was performed. Data extraction and risk of bias assessment was performed independently by two reviewers. The sensitivity of CT and MRI in the detection of LNM was reviewed. Additionally, estimated summary sensitivity, specificity and diagnostic accuracy of MRI were calculated in a patient based meta-analysis. RESULTS: Nine studies including 292 patients were included for narrative synthesis and 5 studies including 158 patients were selected for meta-analysis. Sensitivity of CT ranged from 0.25 to 0.93. Estimated summary diagnostic accuracy parameters of MRI were as follows: sensitivity 0.75 (95% CI 0.6 - 0.85), specificity 0.83 (95% CI 0.74 - 0.90), LR + 4.52 (95% CI 2.55-6.48) and LR- 0.3 (95% CI 0.15 - 0.45). Small (<10 mm) LNM were most frequently undetected on pre-operative imaging. Due to a lack of data, no subgroup analysis comparing the diagnostic accuracy of CT versus MRI could be performed. CONCLUSION: The value of current imaging strategies for the pre-operative assessment of nodal status in GBC remains unclear, especially regarding the detection of small LNM. Additional research is warranted in order to establish uniformity in international guidelines, improve pre-operative nodal staging and to prevent futile surgery.

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.

[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.

Neuralgic amyotrophy associated with temporary vocal fold paralysis: successful treatment by vocal fold augmentation with hyaluronic acid.

BACKGROUND: Neuralgic amyotrophy is a polyneuropathy that classically involves the brachial plexus. This paper reports an unusual clinical manifestation associated with vocal fold paralysis. CASE REPORT: A 36-year-old male presented with hoarseness and progressive weakness of the right shoulder and upper arm muscles. Laryngoscopy revealed a limited adduction of the right vocal fold. RESULTS: Subsequent speech therapy did not improve the symptoms. Therefore, vocal fold augmentation by application of hyaluronic acid in the right vocal fold was performed. CONCLUSION: Vocal fold augmentation with resorbable material seems to be a more effective transient treatment than speech therapy alone for patients with neuralgic amyotrophy and laryngeal involvement.

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.

Delayed recovery from Cheyne-Stokes respiration in heart failure after successful cardiac transplantation: a case report.

BACKGROUND: Sleep-disordered breathing (SDB), especially central sleep apnea with Cheyne-Stokes respiration (CSA-CSR), is highly prevalent in patients with severe heart failure (HF). SDB, and predominantly CSR, may improve after recovery of cardiac function, but available data are limited and inconclusive, particularly in patients who have undergone heart transplantation (HTX). CASE REPORT: The case of a 59-year-old man with dilated cardiomyopathy and advanced chronic HF, plus CSA-CSR, is reported. The patient showed normalization of cardiac function after successful HTX, with delayed but gradual stepwise improvements in CSA-CSR over time. CONCLUSIONS: Although there is a close relationship between cardiac function and manifestations of SDB and CSA-CSR, stabilization of nocturnal respiration after improvement in cardiac function may be delayed rather than immediate.

[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.

[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.