Survival assessment of the extended-wear insulin infusion set featuring lantern technology in adults with type 1 diabetes by the glucose clamp technique.

Maintaining good glycaemic control with the same infusion set for longer than 3 days may improve the quality of life of insulin pump users. The aim of the current study was to assess the efficacy and safety of the novel, extended-wear infusion set over 7 days of wear in adults with type 1 diabetes. Sixteen participants completed three identical 8-hour euglycaemic clamp experiments on Days 1, 4 and 7 of infusion set wear. Between the experiments, the participants were discharged home for routine diabetes management while wearing the same extended-wear infusion set throughout the study. Time to reach the maximum glucose infusion rate (TGIRmax ) on Day 7 was reduced by 67% compared with Day 1 (p < .001). The corresponding area under the glucose infusion rate curve (AUCGIR ) was comparable for the first 2 h of the clamp (p = .891) but decreased by 28% over time (p < .008). While the extent of insulin absorption decreased with prolonged wear, it was accompanied by an increase in insulin absorption rate. The infusion set survival rate was 100% without leakages, occlusion alarms, severe hypoglycaemia or ketoacidosis. The extended-wear infusion set proved safe and effective during prolonged wear in real-life conditions.

Characterization of the endolysosomal system in human chordoma cell lines: is there a role of lysosomes in chemoresistance of this rare bone tumor?

Chordoma is a rare tumor of the bone derived from remnants of the notochord with pronounced chemoresistance. A common feature of the notochord and chordoma cells is distinct vacuolization. Recently, the notochord vacuole was described as a lysosome-related organelle. Since lysosomes are considered as mediators of drug resistance in cancer, we were interested whether they may also play a role in chemoresistance of chordoma. We characterized the lysosomal compartment in chordoma cell lines by cytochemistry, electron microscopy (ELMI) and mutational analysis of genes essential for the physiology of lysosomes. Furthermore, we tested for the first time the cytotoxicity of chloroquine, which targets lysosomes, on chordoma. Cytochemical stainings clearly demonstrated a huge mass of lysosomes in chordoma cell lines with perinuclear accumulation. Also vacuoles in chordoma cells were positive for the lysosomal marker LAMP1 but showed no acidic pH. Genetic analysis detected no apparent mutation associated with known lysosomal pathologies suggesting that vacuolization and the huge lysosomal mass of chordoma cell lines is rather a relict of the notochord than a result of transformation. ELMI investigation of chordoma cells confirmed the presence of large vacuoles, lysosomes and autophagosomes with heterogeneous ultrastructure embedded in glycogen. Interestingly, chordoma cells seem to mobilize cellular glycogen stores via autophagy. Our first preclinical data suggested no therapeutically benefit of chloroquine for chordoma. Even though, chordoma cells are crammed with lysosomes which are according to their discoverer de Duve "cellular suicide bags". Destabilizing these "suicide bags" might be a promising strategy for the treatment of chordoma.

Impact of polar body biopsy on embryo morphokinetics-back to the roots in preimplantation genetic testing?

PURPOSE: Polar body biopsy (PBB) is a common technique in preimplantation genetic testing (PGT) to assess the chromosomal status of the oocyte. Numerous studies have been implemented to investigate the impact of biopsies on embryo development; however, information on embryo morphokinetics is still lacking. Hence, we investigated the impact of PBB on morphokinetic parameters in early embryo development. METHODS: Four hundred four embryos (202 PBB, 202 control) were retrospectively analyzed. Patients were stimulated with a gonadotropin-releasing hormone antagonist ovarian hyperstimulation protocol. After fertilization check, embryos were incubated in a time-lapse incubator. The groups were matched for maternal age at time of oocyte retrieval. RESULTS: Mean group times for reaching specific developmental time points showed no significant difference comparing embryos with PBB conducted and without. Likewise, further subdivision of the PBB group in euploid and aneuploid embryos revealed no differences in the early embryo morphokinetic development compared to the control group. Aneuploidy testing revealed a high prevalence of chromosomal aberrations for chromosomes 21, 4, 16, and 19. CONCLUSIONS: In conclusion, PBB does not impact the morphokinetic parameters of the embryo development. PBB can be safely applied without the risk of impairing the reproductive potential of the embryo and can be highly recommended as safe and practicable PGT approach, especially in countries with prevailing restrictions regarding PGT analysis.

Calcification score evaluation in patients listed for renal transplantation.

Based on native CT scans of the pelvic region using a standardized calcification score, evaluation of iliac vascular calcification was performed between 2008 and 2012 prior to listing for renal transplantation in 205 patients with chronic kidney disease. Vascular calcification showed a decrease from proximal to distal. The difference between the degree of calcification in the common iliac artery and in the external iliac artery was significant (P<.001). Risk factors for total iliac vascular calcification were age, smoking, sex, underlying renal disease, and diabetes. Multivariate analysis revealed age to be the most relevant risk factor (P<.001). The duration of hemodialysis correlated significantly with total iliac vascular calcification. As the introduction of the standardized surgical evaluation protocol, no transplantation has had to be broken off and no early graft loss due to calcification has occurred. Thus, careful scoring of vascular calcification prior to transplantation may be a valuable tool to support surgical decisions and to improve patient safety and outcome in increasingly older transplant recipients.

Neutrophil/Lymphocyte ratio has no predictive or prognostic value in breast cancer patients undergoing preoperative systemic therapy.

BACKGROUND: The primary goal of preoperative systemic treatment (PST) in patients with breast cancer is downsizing of tumors to enhance the rate of breast conserving surgery. Additionally, preoperative systemic treatment offers the possibility to assess for chemosensitivity of early stage disease. In various cancers the prognostic value of neutrophil/lymphocyte ratio (NLR) was demonstrated, indicating that high NLR determines worse prognosis of the patients. The goal of our study was to evaluate the predictive and prognostic value of NLR in early stage breast cancer patients undergoing PST. METHODS: 247 female patients with histologically proven breast cancer were analysed in this retrospective analysis. The NLR before the initiation of PST was documented. Histopathological response in surgically removed specimens was evaluated using a modified Sinn regression score and the pCR defined as no invasive tumor in primary tumor and lymph nodes. NLR was correlated with response to PST and disease free survival. RESULTS: PST was categorized into five groups (anthracycline containing, anthracycline and taxane containing, taxane containing, hormone treatment and other chemotherapies). pCR rate was defined as no invasive rest of tumor either in primary tumor or (ypT0 = Sinn) or in primary tumor and in lymph nodes (ypT0isypN0). Median NLR in patients without any invasive tumor rest was significantly higher than in patients either with some invasive tumor rest or not responding to chemotherapy. Despite this primary difference, the results were not stable across the analysed treatment groups particularly in the group with highest pCR rates (taxane and anthracycline treatment). Further, no association with disease free survival could be observed. CONCLUSIONS: Although there was a reverse trend with the higher NLR prior to systemic treatment in patients who achieved pCR, we could not demonstrate predictive or prognostic value of NLR in the cohort of early stage breast cancer patients treated with PST.

Assessment of vision-related quality of life in patients with central retinal artery occlusion.

BACKGROUND: Central retinal artery occlusion (CRAO) is a major cause for severe visual impairment. Its effect on vision-related quality of life has not yet been determined. The purpose of the present study was thus to assess vision-related quality of life in patients with CRAO using the 39-item National Eye Institute Visual Function Questionnaire. METHODS: The case-control study comprised 26 patients with unilateral CRAO and a control group consisting of 26 control subjects, matched for age and sex. Vision-related quality of life was measured using the 39-item National Eye Institute Visual Function Questionnaire. RESULTS: After Bonferroni correction, the median 39-item National Eye Institute Visual Function Questionnaire composite score was significantly lower in patients with CRAO than in those in the control group (P(corr) < 0.001). Patients with CRAO showed significantly lower median scores in 9 of 12 subscales: general vision (P(corr) < 0.001), peripheral vision (P(corr) < 0.001), difficulties with near-vision activities (P(corr) < 0.001), difficulties with distance-vision activities (P(corr) < 0.001), role difficulties as a result of vision problems (P(corr) < 0.001), dependency on others because of vision problems (P(corr) < 0.001), limitations in social functioning because of vision problems (P(corr) < 0.001), mental health symptoms because of vision problems (P(corr) < 0.001), and general health (P(corr) = 0.008). CONCLUSION: Our data suggest that vision-related quality of life is reduced in patients with CRAO.

Vocal fold fibroblasts and exposure to vibration in vitro: Does sex matter?

Studies have shown that certain vocal fold pathologies are more common in one sex than the other. This is often explained by differences in the composition of the lamina propria and anatomical differences between female and male vocal folds, resulting in e.g. different fundamental frequencies. Here, we investigated a potential sex-specific voice frequency effect in an in vitro setting using vocal fold fibroblasts from one male and one female donor with and without cigarette smoke extract (CSE) addition. After exposure to either male or female vibration frequency with or without CSE, cells and supernatants were harvested. Gene and protein analysis were performed by means of qPCR, western blot, ELISA and Luminex. We found that exposure of cells to both male and female vibration pattern did not elicit significant changes in the expression of extracellular matrix-, inflammation-, and fibrosis-related genes, compared to control cells. The addition of CSE to vibration downregulated the gene expression of COL1A1 in cells exposed to the female vibration pattern, as well as induced MMP1 and PTGS2 in cells exposed to both female and male vibration pattern. The protein expression of MMP1 and COX2 was found to be significantly upregulated only in cells exposed to CSE and female vibration pattern. To conclude, different vibration patterns alone did not cause different responses of the cells. However, the female vibration pattern in combination with CSE had a tendency to elicit/maintain more pro-inflammatory responses in cells than the male vibration pattern.

Bilateral Functional Electrical Stimulation for the Treatment of Presbyphonia in a Sheep Model.

OBJECTIVES: The aim of the study was to increase muscle volume and improve phonation characteristics of the aged ovine larynx by functional electrical stimulation (FES) using a minimally invasive surgical procedure. METHODS: Stimulation electrodes were placed bilaterally near the terminal adduction branch of the recurrent laryngeal nerves (RLN). The electrodes were connected to battery powered pulse generators implanted subcutaneously at the neck region. Training patterns were programmed by an external programmer using a bidirectional radio frequency link. Training sessions were repeated automatically by the implant every other day for 1 week followed by every day for 8 weeks in the awake animal. Another group of animals were used as sham, with electrodes positioned but not connected to an implant. Outcome parameters included gene expression analysis, histological assessment of muscle fiber size, functional analysis, and volumetric measurements based on three-dimensional reconstructions of the entire thyroarytenoid muscle (TAM). RESULTS: Increase in minimal muscle fiber diameter and an improvement in vocal efficiency were observed following FES, compared with sham animals. CONCLUSION: This is the first study to demonstrate beneficial effects in the TAM of FES at molecular, histological, and functional levels. FES of the terminal branches of the RLN reversed the effects of age-related changes and improved vocal efficiency. LEVEL OF EVIDENCE: NA Laryngoscope, 134:848-854, 2024.

Homocysteine contributes to atherogenic transformation of the aorta in rabbits in the absence of hypercholesterolemia.

Atherosclerosis, the leading cause of cardiovascular disease, cannot be sufficiently explained by established risk factors, including cholesterol. Elevated plasma homocysteine (Hcy) is an independent risk factor for atherosclerosis and is closely linked to cardiovascular mortality. However, its role in atherosclerosis has not been fully clarified yet. We have previously shown that rabbits fed a diet deficient in B vitamins and choline (VCDD), which are required for Hcy degradation, exhibit an accumulation of macrophages and lipids in the aorta, aortic stiffening and disorganization of aortic collagen in the absence of hypercholesterolemia, and an aggravation of atherosclerosis in its presence. In the current study, plasma Hcy levels were increased by intravenous injections of Hcy into balloon-injured rabbits fed VCDD (VCDD+Hcy) in the absence of hypercholesterolemia. While this treatment did not lead to thickening of aortic wall, intravenous injections of Hcy into rabbits fed VCDD led to massive accumulation of VLDL-triglycerides as well as significant impairment of vascular reactivity of the aorta compared to VCDD alone. In the aorta intravenous Hcy injections into VCDD-fed rabbits led to fragmentation of aortic elastin, accumulation of elastin-specific electron-dense inclusions, collagen disorganization, lipid degradation, and autophagolysosome formation. Furthermore, rabbits from the VCDD+Hcy group exhibited a massive decrease of total protein methylated arginine in blood cells and decreased creatine in blood cells, serum and liver compared to rabbits from the VCDD group. Altogether, we conclude that Hcy contributes to atherogenic transformation of the aorta not only in the presence but also in the absence of hypercholesterolemia.

Comparison of the 2002 and 2010 TNM classification systems regarding outcome prediction in clear cell and papillary renal cell carcinoma.

AIMS: A novel version of the tumour-node-metastasis (TNM) classification system for renal cell carcinoma (RCC) was introduced in 2010, although the prognostic significance with regard to different histological subtypes has not been explored. Therefore, the aim of our study was to compare the predictive ability of the 2002 and 2010 versions of the TNM classification system for clear cell and papillary RCC. METHODS AND RESULTS: Data from 2263 consecutive clear cell and 309 papillary RCC patients, operated at a single tertiary academic centre, were evaluated. According to TNM 2010, statistically significant differences for cancer-specific survival (CSS) were observed for pT1a versus pT1b (P < 0.001) and pT3a versus pT3b (P < 0.004) in clear cell RCC; and pT1b versus pT2a (P = 0.002) and pT3b versus pT3c (P = 0.046) in papillary RCC. The c-index for CSS in clear cell RCC was 0.74 and 0.73, and in papillary RCC 0.79 and 0.78, for the 2002 and 2010 versions of the TNM classification system, respectively. CONCLUSIONS: According to our data, the predictive ability of the 2010 version of the TNM classification system regarding CSS is not superior to the 2002 version, either in clear cell or in papillary RCC.

Predictive ability of the 2002 and 2010 versions of the Tumour-Node-Metastasis classification system regarding metastasis-free, cancer-specific and overall survival in a European renal cell carcinoma single-centre series.

OBJECTIVE: To compare the predictive ability of the Tumour-Node-Metastasis (TNM) classification systems for renal cell carcinoma (RCC) using three different endpoints: metastasis-free (MFS); overall (OS); and cancer-specific survival (CSS). PATIENTS AND METHODS: Data from 2739 consecutive patients with RCC, who underwent surgery at a single academic centre, were evaluated using multivariate Cox proportional models, Harrell's concordance (c)-index and by applying decision curve analysis (DCA) with regard to MFS, OS and CSS. RESULTS: According to TNM 2010, significant differences for MFS were observed for pT1a vs pT1b, pT1b vs pT2a, pT3a vs pT3b and pT3b vs pT3c stages, respectively (all P < 0.05). With regard to OS, significant differences could be observed in pT1a vs pT1b and pT3a vs pT3b stages, respectively (all P < 0.05). The c-index for CSS, OS and MFS was slightly higher for the 2002 than for the 2010 version of the TNM classification system. Non-inferiority of the 2002 TNM system is supported by the results of the DCA. CONCLUSION: According to our data, the predictive ability of the 2010 version of the TNM classification system regarding three different clinical endpoints is not superior to the 2002 version of this staging system.

Phototherapeutic hardening modulates systemic cytokine levels in patients with polymorphic light eruption.

The etiopathogenesis of polymorphic light eruption (PLE) has been linked to impaired UV-immunosuppression, Langerhans cell (LC) retention, and an absence of neutrophil infiltration into UV-exposed PLE skin. We have previously shown that photohardening restores the impaired neutrophil responsiveness to the chemoattractants leucotriene B4 and formyl-methionyl-leucyl-phenylalanin in PLE patients. The aim of this study was to investigate whether photohardening modulates baseline chemokine and cytokine levels which would alter chemoresponsiveness and hence immune function in PLE patients. Sixteen PLE patients received photohardening therapy for 4-9 weeks by 311 nm UVB. Plasma samples were taken both before and within 48 h of the penultimate phototherapeutic exposure. Plasma from these 16 patients, 8 non-irradiated PLE patients, and 14 control subjects was analyzed for IL-1ß, CXCL8 (IL-8), IL-10, IL-17, TNF, CCL2 (MCP-1), CCL5 (RANTES), CCL11 (eotaxin), and CCL22 (MDC). These cytokines and chemokines were measured in early spring (March to April) and again in late spring (April to June). PLE patients had a significantly elevated level of CCL11 (p = 0.003) and IL-1ß (p = 0.002) in early spring (before phototherapy). In late spring, after phototherapy, PLE patients had significantly elevated CCL2 (p = 0.002) and TNF (p = 0.002) but a trend for lowered plasma levels of CXCL8 (p = 0.021). When comparing the cytokine shifts from early to late spring, while healthy controls and non-UV-irradiated PLE patients showed an increase, PLE patients undergoing photohardening exhibited a trend for decrease in IL-1ß (p = 0.012). Taken together, our results indicate that photohardening may alter the complex cytokine milieu in PLE, in particular via IL-1ß, helping to normalise the pathophysiologic response to subsequent UV exposure.

Comparing Effects of Short- and Long-Term Exposure of Cigarette Smoke Extract on Human Vocal Fold Fibroblasts.

OBJECTIVES: To explore the effects of short- and long-term cigarette smoke extract (CSE) stimulation on the expression of extracellular matrix (ECM) components and inflammatory cytokines in an in vitro model for studying Reinke's edema using human vocal fold fibroblasts (hVFF). STUDY DESIGN: Experimental pilot study using intervention with CSE in vitro. METHODS: Immortalized hVFF were pretreated with 5% CSE or control medium over a period of 2 or 8 weeks, followed by a final 3-day incubation time. We evaluated cell proliferation and examined gene and protein expression of control- and CSE-treated cells using quantitative polymerase chain reaction, Western Blot and enzyme linked immunosorbent assay. RESULTS: Cell numbers of CSE-treated hVFF strongly decreased after 8 weeks and limited the overall duration of the experiment. We observed significant upregulations in gene expression and protein levels of inflammatory markers (cyclooxygenase COX1, COX2) and ECM components (decorin, matrix metalloproteinase 1, transglutaminase 2, gremlin 2) induced by CSE after 2 and 8 weeks. Interleukin 1 receptor 1, prostaglandin I2 synthase, collagen- and hyaluronan-related gene expression showed minor upregulations. The majority of the observed genes were similarly regulated at both time points. However, the CSE-induced mRNA level of COX1 was ablated after 8 weeks. CONCLUSION: Long-term treatment did not yield results significantly different from the short-term protocol. Therefore, we propose that prolonged CSE exposure is not superior to short-term settings, which save both time and materials.

Human Milk Oligosaccharides in Maternal Serum Respond to Oral Glucose Load and Are Associated with Insulin Sensitivity.

(1) Background: Pregnancy presents a challenge to maternal glucose homeostasis; suboptimal adaptations can lead to gestational diabetes mellitus (GDM). Human milk oligosaccharides (HMOs) circulate in maternal blood in pregnancy and are altered with GDM, suggesting influence of glucose homeostasis on HMOs. We thus assessed the HMO response to glucose load during an oral glucose tolerance test (OGTT) and investigated HMO associations with glucose tolerance/insulin sensitivity in healthy pregnant women. (2) Methods: Serum of 99 women, collected at 0 h, 1 h and 2 h during a 75 g OGTT at 24-28 gestational weeks was analyzed for HMOs (2'FL, 3'SLN, LDFT, 3'SL) by HPLC; plasma glucose, insulin and C-peptide were analyzed by standard biochemistry methods. (3) Results: Serum 3'SL concentrations significantly increased from fasting to 1 h after glucose load, while concentrations of the other HMOs were unaltered. Higher 3'SL at all OGTT time points was associated with a generally more diabetogenic profile, with higher hepatic insulin resistance (HOMA-IR), lower insulin sensitivity (Matsuda index) and higher insulin secretion (C-peptide index 1). (4) Conclusions: Rapid increase in serum 3'SL post-oral glucose load (fasted-fed transition) indicates utilization of plasma glucose, potentially for sialylation of lactose. Associations of sialylated HMOs with a more diabetogenic profile suggest sustained adaptations to impaired glucose homeostasis in pregnancy. Underlying mechanisms or potential consequences of observed HMO changes remain to be elucidated.

Distinct maternal amino acids and oxylipins predict infant fat mass and fat-free mass indices.

Interested in maternal determinants of infant fat mass index (FMI) and fat-free mass index (FFMI), considered as predictors for later development of obesity, we analysed amino acids (AA) and oxylipins in maternal serum and breast milk (BM). FMI and FFMI were calculated in 47 term infants aged 4 months (T4). Serum AA were analysed in pregnancy (T1, T2) and 6-8 weeks postpartum (T3). At T3, AA and oxylipins were analysed in BM. Biomarker-index-associations were identified by regression analysis. Infant FMI (4.1 ± 1.31 kg/m2; MW ± SD) was predicted by T2 proline (R2 adj.: 7.6%, p = .036) and T3 BM 11-hydroxy-eicosatetraenoic-acid (11-HETE) and 13-hydroxy-docosahexaenoic-acid (13-HDHA; together:35.5% R2 adj., p < .001). Maternal peripartum antibiotics (AB) emerged as confounders (+AB: 23.5% higher FMI; p = .025). Infant FFMI (12.1 ± 1.19 kg/m2; MW ± SD) was predicted by histidine (R2 adj.: 14.5%, p < .001) and 17-HDHA (BM, R2 adj.:19.3%, p < .001), determined at T3. Confirmed in a larger cohort, the parameters could elucidate connections between maternal metabolic status, nutrition, and infant body development.

Prognostic value of the Leibovich prognosis score supplemented by vascular invasion for clear cell renal cell carcinoma.

PURPOSE: We assessed whether supplementing the Leibovich prognosis score with vascular invasion would improve prognostic value to predict metastatic disease in patients with nonmetastatic clear cell renal cell carcinoma. MATERIALS AND METHODS: We retrospectively evaluated the pathology records of 1,754 patients with nonmetastatic clear cell renal cell carcinoma treated with surgery between 1984 and 2006 at a single tertiary academic center. The Leibovich prognosis score was supplemented by additional scoring for vascular invasion. Metastasis-free survival was assessed using the Kaplan-Meier method for each score category. A Cox regression model was used for multivariate testing. Predictive accuracy was determined by the Harrell concordance index and decision curve analysis. RESULTS: Median followup was 84 months. Ten-year metastasis-free survival probability for a score of 0 to 1 and 2 to 8 or greater was 95%, 83%, 78%, 81%, 69%, 51%, 15% and 13%, respectively. The concordance index was 0.792 compared to 0.778 from our external validation of the Leibovich prognosis score using routine pathological findings (p <0.05). Decision curve analysis also favored the predictive ability of the novel model. CONCLUSIONS: Adding vascular invasion improved the predictive accuracy of our validation data by 1.4% over that of the Leibovich prognosis score. Patients with a score of 7 or greater had a more than 85% probability of metastatic disease at 10 years. Thus, they could be considered candidates for adjuvant treatment trials.

Deficiency of B vitamins leads to cholesterol-independent atherogenic transformation of the aorta.

Atherosclerosis, the leading cause of cardiovascular disease responsible for the majority of deaths worldwide, cannot be sufficiently explained by established risk factors, including hypercholesterolemia. Elevated plasma homocysteine is an independent risk factor for atherosclerosis and is strongly linked to cardiovascular mortality. However, the role of homocysteine in atherosclerosis is still insufficiently understood. Previous research in this area has been also hampered by the lack of reproducible in vivo models of atherosclerosis that resemble the human situation. Here, we have developed and applied an automated system for vessel wall injury that leads to more homogenous damage and more pronounced atherosclerotic plaque development, even at low balloon pressure. Our automated system helped to glean vital details of cholesterol-independent changes in the aortic wall of balloon-injured rabbits. We show that deficiency of B vitamins, which are required for homocysteine degradation, leads to atherogenic transformation of the aorta resulting in accumulation of macrophages and lipids, impairment of its biomechanical properties and disorganization of aortic collagen/elastin in the absence of hypercholesterolemia. A combination of B vitamin deficiency and hypercholesterolemia leads to thickening of the aorta, decreased aortic water diffusion, increased LDL-cholesterol and impaired vascular reactivity compared to any single condition. Our findings suggest that deficiency of B vitamins leads to atherogenic transformation of the aorta even in the absence of hypercholesterolemia and aggravates atherosclerosis development in its presence.

Vitamin D status is associated with disease-free survival and overall survival time in patients with squamous cell carcinoma of the upper aerodigestive tract.

UNLABELLED: Considerable clinical and experimental data suggest that vitamin D plays a role in pathogenesis and progression of cancer; nevertheless clinical data for head and neck squamous cell carcinoma (HNSCC) are not available. The aim of our study was to associate tumor and clinical characteristics with status of vitamin D [25-hydroxyvitamin D (25(OH)D)]. 88 patients with newly diagnosed squamous cell carcinoma of the head and neck were included in the study. A blood draw was taken at the time of diagnosis. The observation period lasted from 2006 until 2010. RESULTS: When compared to a cohort from an epidemiological study, serum levels of 25(OH)D were significantly reduced in patients with HNSCC. We furthermore found disease-free survival, as well as overall survival times to be significantly associated with 25(OH)D levels. In conclusion, results from our study suggest an influence of vitamin D status on cancer incidence, as well as on mortality of HNSCC.

Functional Electrical Stimulation for Presbyphonia: A Prospective Randomized Trial.

OBJECTIVES: The aim of this prospective study was to examine the effects of transcutaneous functional electrical stimulation (FES) in a group of elderly women with presbyphonia. STUDY DESIGN: Prospective randomized study. METHODS: Fourteen participants were enrolled prospectively and attributed randomly to two different treatment groups, where one group (n = 7) received 8 weeks of training (5 days a week), whereas the other group (n = 7) received 4 weeks of ineffective stimulation, followed by 4 weeks of effective training. Stimulation protocols were established during baseline examination and confirmed with endoscopy to ensure a glottal reaction. Numerous acoustical, vocal, patient-centered, and respiratory parameters were obtained at several time points. RESULTS: Neither 4 weeks nor 8 weeks of functional electrical transcutaneous stimulation led to changes of vocal, acoustical, or respiratory parameters, apart from patient-centered items (Voice Handicap Index 12, Voice-Related Quality of Life), which improved over time. However, there were no differences between the two arms for both items. CONCLUSIONS: Transcutaneous FES over 4 weeks and 8 weeks did not lead to significantly improved objective voice and acoustical parameters, which could be caused by the fact that the muscles of interest cannot be targeted specifically enough. However, we found a significant improvement of subjective voice perception and voice-related quality of life in both groups. We explain this finding with an observer-expectancy effect secondary to the very time-consuming and elaborate study procedures. LEVEL OF EVIDENCE: 1b Laryngoscope, 130:E662-E666, 2020.

Asymptomatic sensitization to hymenoptera venom is related to total immunoglobulin E levels.

BACKGROUND: The detection of specific serum immunoglobulin E (sIgE) to Hymenoptera venoms is an established diagnostic tool to diagnose insect venom hypersensitivity. However, the specificity of sIgE detection is a debated issue. METHODS: In 145 subjects, total IgE (tIgE) and sIgE to Hymenoptera venoms as well as sIgE to rapeseed as a marker of cross-reactive carbohydrate determinants were measured. In addition, an atopy score was determined for each patient. We looked for a possible association between tIgE and the presence of sIgE in subjects with a negative history of large local or systemic reactions to insect stings. RESULTS: Fifteen of 65 subjects (23.1%) with low levels of tIgE (<50 kU/l) had sIgE for bee or wasp venom, and 23 of 47 subjects (48.9%) with a tIgE from 50 to 250 kU/l showed sIgE. The highest rate of asymptomatic sensitization (22 of 33; 66.7%) was found in patients with tIgE levels higher than 250 kU/l. Median sIgE was approximately 4.8 times higher in subjects with tIgE levels above 250 kU/l than in those with tIgE levels <50 kU/l. Interestingly, a significant difference in median tIgE was recorded between individuals with and without sIgE to rapeseed [776.5 kU/l (25, 75% percentiles: 252.5, 2,000.0) vs. 50.5 kU/l (20.1, 172.0), respectively; p < 0001]. CONCLUSION: Specific antibodies are frequently seen in individuals with high tIgE, but appear to be largely irrelevant in clinical terms. This might lead to misdiagnosis in persons with an inconclusive sting history.