Disease control in chronic rhinosinusitis: a qualitative study of patient perspectives.

BACKGROUND: The definition of disease control in chronic rhinosinusitis (CRS) is an active area of study. However, investigations have not engaged CRS patients in how they think about disease control. This study seeks to understand the patient perspective on CRS disease control. METHODS: Qualitative phenomenological study using constant comparative methodology was applied. The research team conducted 10, one-on-one interviews with CRS patients ranging from 22 to 55 minutes in length. The content of the interview protocol was determined through iterative discussion amongst all authors. Two authors served as coders to identify recurrent themes. Themes were analyzed for meaning and conclusions were summarized. RESULTS: Three recurring themes determined from patients were that (1) use of the terminology control adequately represents this phenomenon, (2) components of control could be classified into four main themes relating to CRS symptomatology, exacerbation of comorbid disease, quality of life and acute exacerbations of CRS, and (3) when patients deem their CRS is uncontrolled they are more willing to escalate their treatment to include escalating their daily maintenance regimen, seeking otolaryngology referral, taking rescue medication or undergoing endoscopic sinus surgery. CONCLUSIONS: CRS patients consider their daily symptoms, the severity and frequency of CRS exacerbations, impact on quality of life as well as exacerbation of comorbid disease when thinking about their disease control. Disease control is a goal of treatment for patients and uncontrolled disease motivates patients to seek further treatment. Physicians should explore all components of CRS control when considering disease status and need for further treatment.

[Olfactory and gustatory disorders]. / Riech- und Schmeckstörungen.

This manuscript aims to provide an overview of the etiology and diagnosis of olfactory and gustatory disorders. Not only are they common with about 5% of the population affected, but olfactory and gustatory disorders have recently gained attention in light of the rising SARS-CoV­2 pandemic: sudden loss of smell and/or taste is regarded as one of the cardinal symptoms. Furthermore, in the early diagnostics of neurodegenerative diseases, olfactory disorders are of great importance. Patients with olfactory dysfunction often show signs of depression. The impact of olfactory/gustatory disorders is thus considerable, but therapeutic options are unfortunately still limited. Following a description of the etiology, the diagnostic and therapeutic options are discussed on the basis of current literature. Potential future treatments are also addressed, e.g. autologous mucosal grafts or olfactory implants.

Individual importance of olfaction decreases with duration of smell loss.

BACKGROUND: The personal importance of a lost neurologic - motor or sensory - function in several conditions has been shown to decrease as the afflicted patient becomes accustomed to not having that function. It is unknown how the importance of olfaction changes with duration of olfactory dysfunction (OD). The aim of this study was to evaluate the association between duration of smell loss and individual significance of olfaction, and whether this relationship would be modulated by other factors, such as etiology of smell loss. METHODS: This is a retrospective study including a total 163 subjects with different degrees of olfactory function. Individual significance of olfaction was measured using the Importance of Olfaction Questionnaire (IOQ). Demographics, olfactory function, duration and etiology of OD were evaluated. Group comparisons, bivariate correlations, analyses of variance and multivariate linear regression were applied to detect differences and associations with the outcome measure of IOQ. RESULTS: A significant negative correlation was found between duration of OD and the IOQ. Other important findings include a significantly higher IOQ in patients with posttraumatic- compared to idiopathic OD and in patients with higher aggravation scores compared to the lower aggravation group. Multivariate regression analysis further confirmed that duration of smell loss was independently associated with IOQ. CONCLUSIONS: The duration of smell loss is negatively correlated with the individual importance of olfaction, suggesting that patients develop coping mechanisms for adjusting to OD.

EPOS 4 Patients.

EPOS2020 is the 4th and most recent version of the European Position Paper on Rhinosinusitis and Nasal Polyps which was first published in 2005. It aims to provide the most up to date scientifically robust information on the topic published in the literature which has been critically analysed by an international group of clinicians drawn from all disciplines dealing with these problems together with patients. The guidelines offer evidence-based recommendations and care pathways for acute and chronic rhinosinusitis in both adults and children. Management of these diseases from the patients' perspective is an important part of EPOS2020. Not only is this included in the main document but, for the first time, we have produced a separate supplement dedicated to and in collaboration with patients, EPOS4Patients, which aims to provide information in an accessible format, to answer frequently asked questions about these diseases and their treatment options as well as including useful patient resources and websites. It has never been more important for patients to be actively involved in their care. Being well informed helps you to make the best decisions together with your doctor.

Validity of systemic antibiotics and systemic corticosteroid usage for chronic rhinosinusitis as metrics of disease burden.

BACKGROUND: The frequencies of systemic antibiotics and oral corticosteroids taken for chronic rhinosinusitis (CRS) indicate poor CRS disease control. We sought to determine the validity and responsiveness of these metrics as reflections of CRS disease burden. METHODOLOGY: One hundred and eighty-seven patients undergoing medical management for CRS were recruited. Participants were assessed at two time points: enrollment and a follow-up appointment three to nine months later. At each time point, CRS related antibiotic and oral corticosteroid usage in the previous three months was measured, while general and disease-specific quality of life (QOL) was measured using the visual analog scale of the 5-dimension EuroQol questionnaire (EQ-5D VAS) and the 22-item Sinonasal Outcome Test (SNOT-22), respectively. RESULTS: The frequency of CRS-related antibiotics and oral corticosteroids use was cross-sectionally correlated with EQ-5D VAS and SNOT-22 at the corresponding time points. For participants reporting usage of these medications at enrollment, there was a decrease of 1 course per 3 months for both CRS-related antibiotics and oral corticosteroids. Change in CRS-related antibiotics from enrollment to follow-up was correlated with change in both EQ-5D and SNOT-22 over the same timeframe. The change in CRSrelated oral corticosteroids was correlated with change in both EQ-5D VAS and SNOT-22). These correlations were stronger in the subset of patients who had a change in these metrics over the study period. CONCLUSIONS: The frequencies of CRS-related antibiotic use and oral corticosteroid use are valid and responsive measures of CRS disease burden.

Responsiveness and minimal clinically important difference for the EQ-5D in chronic rhinosinusitis.

BACKGROUND: The 5-dimensional EuroQol questionnaire (EQ-5D) is validated to measure general health-related quality of life (QOL). Our objective was to determine the responsiveness and minimal clinically important difference (MCID) of the EQ-5D health utility value (EQ-5D HUV) and visual analog scale (EQ-5D VAS) in chronic rhinosinusitis (CRS). METHODS: 203 adults undergoing medical management for CRS were prospectively recruited. General health-related QOL (using EQ-5D HUV and EQ-5D VAS) and CRS-specific QOL (using the 22-item Sinonasal Outcome Test [SNOT-22]) were measured at enrollment and a subsequent follow-up time point 2-12 months later. At follow-up, participants also rated change in general health as Much worse, A little worse, About the same, A little better or Much better compared to enrollment. The EQ-5D HUV and EQ-5D VAS MCIDs were calculated using distribution-based, anchor-based, and receiver operator characteristic (ROC) curve-based methods. RESULTS: Change in SNOT-22 score was correlated with EQ-5D HUV and EQ-5D VAS change. Using the different methods of calculating MCID, we find the EQ-5D HUV MCID to be 0.04 and EQ-5D VAS MCID to be 8.0. The calculated EQ-5D MCIDs had approximately a sensitivity of 40-50% and specificity of 80% in detecting patients experiencing noticeable improvement in general health. CONCLUSIONS: The EQ-5D responds well to changing CRS symptomatology. We propose MCIDs for EQ-5D HUV of 0.04 and EQ-5D VAS of 8 in CRS patients, which although specific, are not sensitive for detecting patients experiencing improvement in general health.

Cardiac markers (BNP, NT-pro-BNP, Troponin I, Troponin T, in female amateur runners before and up until three days after a marathon.

PURPOSE: Transient cardiac ventricular dysfunction or sudden cardiac deaths have been reported for male athletes participating in marathon racing. Less is known about the myocardial response in females. We examined natriuretic peptides and cardiac troponins in female athletes after a marathon. METHODS: At the 31st real,- Berlin Marathon plasma levels of NT-pro-BNP, BNP, cTnI and cTnT were measured in 15 women (age 35+/-6 years; finishing times between 3:22 h and 5:21 h) at four different time points (before, immediately after, day one and day three). RESULTS: An increase in [NT-pro-BNP] was observed immediately after the marathon (median [NT-pro-BNP] before: 39.6 pg ml(-1), after: 138.6 pg ml(-1), p=0.003) with a further increase on day one. [BNP] did not increase immediately after the marathon but increased on day one (median [BNP] before: 15 pg ml(-1), day one: 27.35 pg ml(-1), p=0.006). On day three, [NT-pro-BNP] and [BNP] returned to initial values. [cTnI] was under the detection limit prior to the marathon in all runners. [cTnT] was under the detection limit before the marathon except in one runner who presented a concentration of 0.03 ng ml(-1). Cardiac troponins (median [cTnl] after: 0.098 ng ml(-1), p=0.028; median [cTnT] after: 0.032 ng ml(-1), p=0.012) increased immediately after the marathon and returned to initial values on day one [cTnT] and three [cTnI]. DISCUSSION: Parameters representing cardiac stress increased in females after a marathon. Different kinetics of natriuretic peptides BNP and NT-pro-BNP post-marathon could be due to their different half-lives and dependence on renal function. The increase of cTnI and cTnT may result from minor myocardial lesions.

Primary intra-articular epithelioid sarcoma of the knee: Unusual presentation of a rare entity.

We report a case of a 60-year-old female with severe and progressive pain of her right knee. Physical therapy, pain medication, and arthroscopic debridement were unsuccessful. Finally, pathological examination revealed an intra-articular epithelioid sarcoma, a rare tumor in an atypical location. Patient died within 5 months after initial admission. Despite this unusual clinical course and presentation, we would like to share the valuable clinical lessons we learned from this case. Introduction of a coordinating physician in combination with a multidisciplinary treatment regarding optimal pain management should optimize treatment results in future patients.

Bilateral vanishing hips, coincidence or systemic disease? A case report and overview of current literature.

Rapidly progressive hip disease (RDHD) is a rare condition of the hip joint, causing destruction of the femoral head. The pathogenesis is unknown. The disease is self-limiting, there is no treatment to stop the disease. Hip arthroplasty is a successful way to relieve pain and restore function. We present a case where both hips were involved and analysed. A favourable result was obtained by bilateral total hip arthroplasty.

Arabinoxylan consumption decreases postprandial serum glucose, serum insulin and plasma total ghrelin response in subjects with impaired glucose tolerance.

OBJECTIVE: Arabinoxylan (AX) consumption is associated with metabolic improvement during diabetes and with modulation of ghrelin, an orexigenic gut hormone. The effect of AX consumption on ghrelin secretion in disturbed metabolic states is unknown. Therefore, we investigated the postprandial responses to AX consumption of serum glucose, insulin and triglycerides and plasma total and acylated ghrelin in subjects with impaired glucose tolerance (IGT). DESIGN: Randomized, single-blind, controlled, crossover intervention trial. SUBJECTS: Seven female and four male adults with IGT, aged 55.5 years, and body mass index (BMI) 30.1 kg/m(2). INTERVENTION: Subjects received either placebo or 15 g AX supplement for 6 weeks with a 6-week washout period in-between. MAIN OUTCOME MEASUREMENTS: Postprandial responses of serum glucose, insulin and triglycerides, and plasma total and acylated ghrelin after a liquid meal challenge test (LMCT) measured at the beginning and at the end of the dietary intervention at -20, -5, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min. RESULTS: After LMCT, AX consumption resulted in lower postprandial responses in serum glucose, insulin and triglycerides (P<0.05). Compared to placebo, total plasma ghrelin was also reduced by 42+/-8 pg/ml (P<0.001) after AX consumption with no difference in plasma acylated ghrelin. CONCLUSION: AX consumption improved postprandial metabolic responses after an LMCT in subjects with IGT and reduced total ghrelin response. However, acylated ghrelin responses were unchanged, suggesting that the acylated ghrelin-mediated orexigenic regulation is not improved as only total plasma ghrelin decreased.

Modulation of the activity of hepatic glucose-6-phosphatase by methylthioadenosine sulfoxide.

Methylthioadenosine sulfoxide (MTAS), an oxidized derivative of the cell toxic metabolite methylthioadenosine has been used in elucidating the relevance of an interrelationship between the catalytic behavior and the conformational state of hepatic glucose-6-phosphatase and in characterizing the transmembrane orientation of the integral unit in the microsomal membrane. The following results were obtained: (1) Glucose 6-phosphate hydrolysis at 37 degrees C is progressively inhibited when native microsomes are treated with MTAS at 37 degrees C. In contrast, glucose 6-phosphate hydrolysis of the same MTAS-treated microsomes assayed at 0 degrees C is not inhibited. (2) Subsequent modification of the MTAS-treated microsomes with Triton X-114 reveals that glucose-6-phosphatase assayed at 37 degrees C as well as at 0 degrees C is inhibited. (3) Although excess reagent is separated by centrifugation and the MTAS-treated microsomes diluted with buffer before being modified with Triton the temperature-dependent effect of MTAS on microsomal glucose-6-phosphatase is not reversed at all. (4) In native microsomes MTAS is shown to inhibit glucose-6-phosphatase noncompetitively. The subsequent Triton-modification of the MTAS-treated microsomes, however, generates an uncompetitive type of inhibition. (5) Preincubation of native microsomes with MTAS completely prevents the inhibitory effect of 4,4'-diisothiocyanostilbene 2,2'-disulfonate (DIDS) as well as 4,4'-diazidostilbene 2,2'-disulfonate (DASS) on glucose-6-phosphatase. (6) Low molecular weight thiols and tocopherol protect the microsomal glucose-6-phosphatase against MTAS-induced inhibition. (7) Glucose-6-phosphatase solubilized and partially purified from rat liver microsomes is also affected by MTAS in demonstrating the same temperature-dependent behavior as the enzyme of MTAS-treated and Triton-modified microsomes. From these results we conclude that MTAS modulates the enzyme catalytic properties of hepatic glucose-6-phosphatase by covalent modification of reactive groups of the integral protein accessible from the cytoplasmic surface of the microsomal membrane. The temperature-dependent kinetic behavior of MTAS-modulated glucose-6-phosphatase is interpreted by the existence of distinct catalytically active enzyme conformation forms. Detergent-induced modification of the adjacent hydrophobic microenvironment additionally generates alterations of the conformational state leading to changes of the kinetic characteristics of the integral enzyme.

Is thermostability of glucose-6-phosphatase indeed dependent on a stabilizing protein?

Partial purification of glucose-6-phosphatase from rat liver microsomes by solubilization of the membranes with the non-ionic detergent Triton X-114 at pH 6.5 and the removal of inactivating detergent by hydrophobic chromatography results in a thermostable enzyme protein which is not dependent on stabilizing phospholipids or proteins. The readdition of low amounts of detergent immediately causes a conversion into a thermo-unstable phosphohydrolase protein. Thus these findings present evidence that heat instability of partially purified glucose-6-phosphatase derives from traces of inactivating detergent changing the structural properties of the phosphohydrolase rather than from the absence of the postulated specific stabilizing protein.

Stabilisation of strawberry (Fragaria x ananassa Duch.) anthocyanins by different pectins.

The objective of the present study was to evaluate the effects of different pectins on strawberry anthocyanins in viscous model solutions at pH 3.0. For this purpose, low esterified amidated, low and high methyl esterified citrus and apple pectins, and a sugar beet pectin (SBP), respectively, were added to strawberry extracts. The latter were predominantly composed of pelargonidin-glycosides, containing either reduced (E-1) or original amounts of non-anthocyanin phenolics (E-2). Model systems were stored for 18 weeks at 20±0.5 °C protected from light, and anthocyanins were quantitated in regular intervals by HPLC-DAD analyses. Half-life (t1/2) and destruction (D) values were calculated based on first-order kinetics. Generally, significant differences in pigment retention could be ascribed to differing pectin sources, while variation in the degree of esterification and amidation, respectively, had negligible effects. Compared to systems without added pectin, apple pectins and SPB enhanced anthocyanin stability moderately, while stabilising effects of citrus pectins were poor or even imperceptible. Generally, the amount of non-anthocyanin phenolics and the addition of citrate did not markedly affect anthocyanin stability. However, pectins had no influence on total phenolic contents (Folin-Ciocalteu assay) and antioxidant capacities (FRAP and TEAC assay) of strawberry phenolics over time. For pelargonidin-3-glucoside and -rutinoside largely consistent stabilities were found in all model systems. In contrast, pelargonidin-3-malonylglucoside was less stable in the blank, and stabilisation by pectins was always negligible. The findings of the present study are contrary to results reported previously for the stabilisation of cyanidin- and delphinidin-glycosides in similar model systems prepared with black currant extracts, indicating a high impact of the number of hydroxyl groups in the anthocyanin B-ring.

Impact of pectin type on the storage stability of black currant (Ribes nigrum L.) anthocyanins in pectic model solutions.

The effects of different pectins on the stabilisation of black currant anthocyanins in viscous model solutions at pH 3.0 were investigated. For this purpose, low esterified amidated (AM), low (LM) and high (HM) methoxylated citrus and apple pectins and a sugar beet pectin were added to a purified anthocyanin extract (ACN-E) and to an extract containing anthocyanins and non-anthocyanin phenolics (PP-E). Model systems were stored at 20±0.5°C in the dark. Anthocyanin contents were monitored by HPLC analysis over a period of 18 weeks, and half-life and destruction values were calculated. In all pectic model solutions anthocyanin stability was significantly improved compared to stability of the extracts without added pectins (blank). Best stabilisation was obtained with AM pectin, followed by LM and HM pectins. In model systems containing citrus pectins, anthocyanin stabilisation was better compared to that of apple pectins having similar degrees of esterification and amidation, respectively. This was primarily due to the strong interaction of delphinidin glycosides with the citrus pectins, whereas stabilisation of cyanidin derivatives was less important. Sugar beet pectin improved anthocyanin stability only to a limited extent. In the presence of non-anthocyanin phenolics (PP-E) the impact of the pectin source was even more pronounced than the effect of the pectin type. Addition of citrate to pectic systems accelerated anthocyanin decay. Stabilising effects of pectins were hardly noticeable when evaluating total phenolic content (TPC, Folin-Ciocalteu) and antioxidant capacity during storage. Highest TPC, TEAC- and FRAP values were observed in systems containing citrus pectin, which was in contrast to sugar beet pectin, where values fell below those of the blank after storage.

Arabinoxylan fibre consumption improved glucose metabolism, but did not affect serum adipokines in subjects with impaired glucose tolerance.

The consumption of arabinoxylan, a soluble fibre fraction, has been shown to improve glycemic control in type 2 diabetic subjects. Soluble dietary fibre may modulate gastrointestinal or adipose tissue hormones regulating food intake. The present study investigated the effects of arabinoxylan consumption on serum glucose, insulin, lipids, leptin, adiponectin and resistin in subjects with impaired glucose tolerance. In a randomized, single-blind, controlled, crossover intervention trial, 11 adults consumed white bread rolls as either placebo or supplemented with 15 g arabinoxylan for 6 weeks with a 6-week washout period. Fasting serum glucose, insulin, triglycerides, unesterified fatty acids, apolipoprotein A1 and B, adiponectin, resistin and leptin were assessed before and after intervention. Fasting serum glucose, serum triglycerides and apolipoprotein A-1 were significantly lower during arabinoxylan consumption compared to placebo (p=0.029, p=0.047; p=0.029, respectively). No effects of arabinoxylan were observed for insulin, adiponectin, leptin and resistin as well as for apolipoprotein B, and unesterified fatty acids. In conclusion, the consumption of AX in subjects with impaired glucose tolerance improved fasting serum glucose, and triglycerides. However, this beneficial effect was not accompanied by changes in fasting adipokine concentrations.

Increase in serum resistin during weight loss in overweight subjects is related to lipid metabolism.

OBJECTIVE: Human resistin has been stated to influence preadipocyte cell numbers and to stimulate adipocyte triglyceride lipolysis in vivo and in vitro. However, its role in human obesity remains unclear. DESIGN: Cross-sectional study for comparisons of lean and obese subjects, and subsequent longitudinal 4-month weight loss intervention study in obese subjects. SUBJECTS: Healthy subjects, lean (n=20, BMI<25) and overweight (n=43, BMI>or=25). MEASUREMENTS: Serum resistin, body weight, body fat, waist-to-hip ratio, as well as markers of insulin resistance and lipid metabolism at baseline and after 4 months of intervention. RESULTS: Serum resistin was positively correlated to HOMA-IR (partial r=0.288; P=0.055), serum fructosamines (partial r=0.280; P=0.062), serum NEFA (partial r=0.276; P=0.066) and negatively to age (partial r=-0.349; P=0.019) and serum apolipoprotein A-1 (partial r=-0.363; P=0.014). During the intervention, serum resistin increased significantly (P<0.001). The increase was inversely related to changes in waist-to-hip ratio (P=0.025) and positively to serum apolipoprotein B (P=0.011). In males only, the increase in resistin during weight loss was predicted by total serum cholesterol at baseline (r=0.703, P=0.007). No relation was observed between changes in resistin and changes in HOMA-IR. CONCLUSION: The present study indicates an association between serum resistin and markers of abdominal fat distribution as well as the regulation of lipid metabolism. However, human resistin is unlikely to play an independent role in the regulation of glucose metabolism.

On the nature of the interaction between 4,4'-diisothiocyanostilbene 2,2'-disulfonic acid and microsomal glucose-6-phosphatase. Evidence for the involvement of sulfhydryl groups of the phosphohydrolase.

The effect of 4,4'-diisothiocyanostilbene 2,2'-disulfonic acid (DIDS) on microsomal glucose 6-phosphate hydrolysis has been reinvestigated and characterized in order to elucidate the topological and functional properties of the interacting sites of the glucose-6-phosphatase. The studies were performed on microsomal membranes, partially purified and reconstituted glucose-6-phosphatase preparations and show the following. (a) DIDS inhibits activity of the glucose-6-phosphatase of native microsomes as well as the partially purified glucose-6-phosphatase. (b) Inhibition is reversed when the microsomes and the partially purified phosphohydrolase, incorporated into asolectin liposomes, are modified with Triton X-114. (c) Treatment of native microsomes with DIDS and the following purification of glucose-6-phosphatase from these labeled membranes leads to an enzyme preparation which is labeled and inhibited by DIDS. (d) Preincubation of native microsomes or partially purified glucose-6-phosphatase with a 3000-fold excess of glucose 6-phosphate cannot prevent the DIDS-induced inhibition. (e) Inhibition of glucose-6-phosphatase by DIDS is completely prevented when reactive sulfhydryl groups of the phosphohydrolase are blocked by p-mecuribenzoate. (f) Reactivation of enzyme activity is obtained when DIDS-labeled microsomes are incubated with 2-mercaptoethanol or dithiothreitol. Therefore, we conclude that inhibition of microsomal glucose 6-phosphate hydrolysis by DIDS cannot result from binding of this agent to a putative glucose-6-phosphate-carrier protein. Our results rather suggest that inhibition is caused by chemical modification of sulfhydryl groups of the integral phosphohydrolase accessible to DIDS attack itself. An easy interpretation of these results can be obtained on the basis of a modified conformational model representing the glucose-6-phosphatase as an integral channel-protein located within the hydrophobic interior of the microsomal membrane [Schulze et al. (1986) J. Biol. Chem. 261, 16,571-16,578].