Expression of inducible nitric oxide synthase, nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3 in patients with gastroesophageal reflux disease, eosinophilic esophagitis, and in healthy controls: a semiquantitative image analysis of 3,3'-diaminobenzidine-stained esophageal biopsies.

Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) share many histopathological features; therefore, markers for differentiation are of diagnostic interest and may add to the understanding of the underlying mechanisms. The nitrergic system is upregulated in GERD and probably also in EoE. Esophageal biopsies of patients with EoE (n = 20), GERD (n = 20), and healthy volunteers (HVs) (n = 15) were exposed to antibodies against inducible nitric oxide synthase (iNOS), nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3. The stained object glasses were randomized, digitized, and blindly analyzed regarding the expression of DAB (3,3'-diaminobenzidine) by a protocol developed in QuPath software. A statistically significant overexpression of iNOS was observed in patients with any of the two inflammatory diseases compared with that in HVs. Eotaxin-3 could differentiate HVs versus inflammatory states. Gastroesophageal reflux patients displayed the highest levels of nitrotyrosine. Neither iNOS nor nitrotyrosine alone were able to differentiate between the two diseases. For that purpose, eosinophil peroxidase was a better candidate, as the mean levels increased stepwise from HVs via GERD to EoE. iNOS and nitrotyrosine are significantly overexpressed in patients with EoE and GERD compared with healthy controls, but only eosinophil peroxidase could differentiate the two types of esophagitis. The implications of the finding of the highest levels of nitrotyrosine among gastroesophageal reflux patients are discussed.

Validation and psychometric evaluation of the Swedish version of the Nasal Obstruction Symptom Evaluation scale.

Objectives: The Nasal Obstruction Symptom Evaluation (NOSE) scale is a symptom-specific quality-of-life questionnaire for patients suffering from nasal obstruction. The instrument is designed specifically for patients with septal deviation and for the evaluation of the outcome of septoplasty. The aim of this study was to validate a Swedish version of the NOSE instrument for use in clinical practice and research. Methods: A Swedish version of the NOSE was tested in a case group consisting of 125 subjects with nasal obstruction (of which 31 underwent septoplasty) and a control group consisting of 65 healthy subjects. Base line data for the case and control groups were used to evaluate face validity, known groups validity, construct validity, internal consistency and factor structure analysis. Fifty participants in both the case groups and control groups were assessed both at baseline and after 2 weeks to evaluate test-retest reliability. The participants who underwent septoplasty were assessed at baseline and after 3-6 months to evaluate responsiveness. Results: The S-NOSE was found to be reliable, valid, and responsive. Both Cronbach's α and McDonald Omega coefficients were >0.7, and the intra class coefficient was 0.942. The S-NOSE scores were significantly correlated with nasal patency VAS in both the case group and the control group (p < .001 and p = .018, respectively). After septoplasty, the mean S-NOSE score were significantly improved (p < .001). Furthermore, the S-NOSE was shown to have excellent and robust psychometric properties. Conclusion: The S-NOSE can be recommended in both clinical practice and research to evaluate the outcome of septoplasty in Swedish-speaking populations. Level of Evidence: NA.

Treatment with head-lift exercise in head and neck cancer patients with dysphagia: results from a randomized, controlled trial with flexible endoscopic evaluation of swallowing (FEES).

BACKGROUND: This randomized study aimed to evaluate the effects of the Shaker head-lift exercise (HLE) to improve dysphagia following oncologic treatment for head and neck cancer (HNC). METHODS: Patients with dysphagia following oncologic treatment for HNC were randomly assigned to intervention (n = 23) or control (standard dysphagia management, n = 24) groups. Swallowing was evaluated at baseline and at 8-week follow-up using flexible endoscopic evaluation of swallowing (FEES) and self-perceived swallowing with the Eating Assessment Tool (EAT-10). Analysis was performed regarding secretion, initiation of swallow, residue after swallowing, and penetration/aspiration. RESULTS: Few statistically significant differences were found in the FEES analysis. Some improvement of self-perceived swallowing function was found in both groups. Adherence to training was high. CONCLUSIONS: This randomized study regarding the effect of the HLE demonstrated that swallowing outcome measures used in assessment of FEES did not improve in patients treated with radiotherapy for patients with dysphagia following HNC.

Sinonasal Symptoms and Self-Reported Health before and after Endoscopic Pituitary Surgery-A Prospective Study.

Objectives Despite the limited invasiveness of endoscopic transsphenoidal surgery (ETSS), some degree of nasal structure destruction is unavoidable. Our objective was to evaluate sinonasal morbidity and self-reported health before and 6 months after ETSS for pituitary tumors, and to identify possible predictive factors for deterioration in sinonasal health. Design Prospective observational cohort study. Setting University tertiary referral hospital. Participants Totally 109 consecutive adult patients undergoing ETSS for pituitary tumors between 2015 and 2019. Main Outcome Measures Sinonasal symptoms and self-reported health before and 6 months after ETSS, assessed by the Sinonasal Outcome Test (SNOT-22) and the EQ-5D questionnaire. Predictive factors for postoperative deterioration in sinonasal symptoms. Results The overall SNOT-22 score did not change, but the score of the rhinologic domain of SNOT-22 worsened from 6.0 ± 5.9 before to 8.0 ± 7.4 6 months after surgery ( p = 0.011). The EQ-5D visual analog scale improved from 64.0 ± 22.9 before to 71.1 ± 18.7 6 months after surgery ( p = 0.00088). Univariate and multivariable regression analyses showed that prior sinonasal surgery was associated with a significant worsening in rhinologic symptoms 6 months after surgery ( p = 0.046 and p = 0.020, respectively). Conclusions Although self-reported overall health improved, significant deterioration of rhinologic symptoms was seen 6 months after ETSS. This information is important for preoperative patient counselling. Further refinement of the surgical technique and follow-up strategies to reduce postoperative sinonasal morbidity could be of value, especially in patients who have undergone prior sinonasal surgery.

Headache Before and After Endoscopic Transsphenoidal Pituitary Tumor Surgery: A Prospective Study.

Objective Headache is a common symptom among patients with pituitary tumors, as it is in the general population. The aim of the study was to investigate headache as a symptom in patients with pituitary tumors before and 6 months after endoscopic transsphenoidal surgery (TSS). Design This is a prospective observational cohort study. Setting This study was conducted at university tertiary referral hospital. Participants A total of 110 adult patients underwent endoscopic TSS for pituitary tumors. Main Outcome Measures The Migraine Disability Assessment (MIDAS) questionnaire was used before and 6 months after surgery for the assessment of headache. Clinical variables with potential influence on headache were analyzed. Results Sixty-eight (62%) patients experienced headaches at least once during the 3 months before surgery. Thirty (27%) patients reported disabling headache before surgery, with younger age being an independent associated factor ( p < 0.001). In patients with disabling headache before surgery, the median (interquartile range) MIDAS score improved from 78 (27-168) to 16 (2-145; p = 0.049), headache frequency decreased from 45 (20-81) to 14 (4-35) days ( p = 0.009), and headache intensity decreased from 6 (5-8) to 5 (4-7) ( p = 0.011) after surgery. In total, 16 of the 30 (53%) patients reported a clinically relevant improvement and five (17%) a clinically relevant worsening. Four (5%) patients developed new disabling headache. No predictor for postoperative improvement of headache was identified. Conclusion In this prospective study, the results show that disabling headache improves following endoscopic TSS in a subset of patients with pituitary tumors. However, no predictive factors for improvement could be identified.

TTCOV19: timing of tracheotomy in SARS-CoV-2-infected patients: a multicentre, single-blinded, randomized, controlled trial.

BACKGROUND: Critically ill COVID-19 patients may develop acute respiratory distress syndrome and the need for respiratory support, including mechanical ventilation in the intensive care unit. Previous observational studies have suggested early tracheotomy to be advantageous. The aim of this parallel, multicentre, single-blinded, randomized controlled trial was to evaluate the optimal timing of tracheotomy. METHODS: SARS-CoV-2-infected patients within the Region Västra Götaland of Sweden who needed intubation and mechanical respiratory support were included and randomly assigned to early tracheotomy (≤ 7 days after intubation) or late tracheotomy (≥ 10 days after intubation). The primary objective was to compare the total number of mechanical ventilation days between the groups. RESULTS: One hundred fifty patients (mean age 65 years, 79% males) were included. Seventy-two patients were assigned to early tracheotomy, and 78 were assigned to late tracheotomy. One hundred two patients (68%) underwent tracheotomy of whom sixty-one underwent tracheotomy according to the protocol. The overall median number of days in mechanical ventilation was 18 (IQR 9; 28), but no significant difference was found between the two treatment regimens in the intention-to-treat analysis (between-group difference: - 1.5 days (95% CI - 5.7 to 2.8); p = 0.5). A significantly reduced number of mechanical ventilation days was found in the early tracheotomy group during the per-protocol analysis (between-group difference: - 8.0 days (95% CI - 13.8 to - 2.27); p = 0.0064). The overall correlation between the timing of tracheotomy and days of mechanical ventilation was significant (Spearman's correlation: 0.39, p < 0.0001). The total death rate during intensive care was 32.7%, but no significant differences were found between the groups regarding survival, complications or adverse events. CONCLUSIONS: The potential superiority of early tracheotomy when compared to late tracheotomy in critically ill patients with COVID-19 was not confirmed by the present randomized controlled trial but is a strategy that should be considered in selected cases where the need for MV for more than 14 days cannot be ruled out. Trial registration NCT04412356 , registered 05/24/2020.

The effect of the Shaker head-lift exercise on swallowing function following treatment for head and neck cancer: Results from a randomized, controlled trial with videofluoroscopic evaluation.

BACKGROUND: Dysphagia is common following treatment for head and neck cancer (HNC) and intervention to improve swallowing function is warranted. This study aimed to evaluate the efficacy of the Shaker head-lift exercise (HLE) to improve dysphagia in HNC patients. METHODS: Patients treated for HNC with radiochemotherapy and with subsequent dysphagia were randomly assigned to intervention (HLE, n = 25) and control (standard dysphagia management, n = 27) groups. Videofluoroscopic evaluation of penetration-aspiration, initiation, residue, movement of selected structures, and self-perceived swallowing function, before and after 8 weeks of treatment, were compared. RESULTS: Although adherence to training was high, no statistically significant differences in objectively measured swallowing function between the groups or within-group changes were found. Self-perceived swallowing function improved in the intervention group. CONCLUSIONS: In this HNC population, neither HLE nor standard dysphagia management improved objectively measured swallowing function as evaluated after 8 weeks. Future research focusing on finding effective interventions for dysphagia is warranted.

Tracheotomy in COVID-19 patients: A retrospective study on complications and timing.

OBJECTIVES: The aim of this study was to analyze the timing of tracheotomy and the duration of mechanical ventilation and stay in the intensive care unit (ICU) in patients with COVID-19 infection. Furthermore, we aimed to investigate tracheotomy complications and mortality. METHODS: Consecutive patients with COVID-19 infection admitted to the Department of Infectious Diseases in Gothenburg, Sweden were identified. Medical records were retrieved and retrospectively assessed. RESULTS: One hundred eighty-eight patients with COVID-19 infection requiring hospital care were identified. Of these, 116 patients were critically ill and intubated, and 55 patients underwent tracheotomy. The mean time from endotracheal intubation to tracheotomy was 12 days (range 5-28 days). There was a correlation between the timing of tracheotomy and the duration of mechanical ventilation, where a shorter time between intubation and tracheotomy was correlated with a shorter duration of mechanical ventilation (r .58, P < .001), and a correlation was identified between the timing of tracheotomy and the duration of ICU stay (r .52, P < .001). Perioperative hypoxemia was registered in 9% of tracheotomies performed, whereas postoperative bleeding was observed in 27% of cases, the majority of which were minor. CONCLUSIONS: This retrospective cohort study indicates that early tracheotomy is related to a reduced need for mechanical ventilation and a shorter duration of stay in the ICU in severe cases of COVID-19 disease. Complications during and after tracheotomy in this specific cohort included risk perioperative hypoxia and postoperative bleeding. Prospective randomized controlled trials would be of value to confirm these findings. LEVEL OF EVIDENCE: 4, Case series.

Circulating brain injury biomarkers increase after endoscopic surgery for pituitary tumors.

Pituitary tumors and subsequent treatment with endoscopic transsphenoidal surgery (ETSS) may cause injury to suprasellar structures, causing long-term fatigue and neurocognitive impairment. A method to quantify brain injury after ETSS is not available. In this prospective, exploratory study of patients undergoing ETSS for pituitary tumors, a novel approach to detect possible neuronal damage is presented. Plasma concentrations of brain injury biomarkers (glial fibrillary acidic protein [GFAP], tau, and neurofilament light [NFL]) were measured the day before surgery, immediately after surgery, at day 1 and 5, and at 6 and 12 months after surgery, using enzyme-linked immunosorbent assays. The association between the increase of biomarkers with preoperative tumor extension and postoperative patient-perceived fatigue was evaluated. Suprasellar tumor extension was assessed from MRI scans, and self-perceived fatigue was assessed using the Multidimensional Fatigue Inventory before and 6 months after surgery. Thirty-five patients were included in the analysis. Compared to baseline, GFAP showed a maximal increase at day 1 after surgery (p = 0.0005), tau peaked postoperatively on the day of surgery (p = 0.019), and NFL reached its maximum at day 5 after surgery (p < 0.0001). The increase in GFAP correlated with preoperative chiasmal compression (p = 0.020). The increase in tau was correlated with preoperative chiasmal (p = 0.011) and hypothalamus compression (p = 0.016), and fatigue score 6 months after surgery (p = 0.016). In conclusion, the concentrations of brain injury biomarkers in blood increased after ETSS for pituitary tumors. The results indicate that postoperative plasma GFAP and tau might reflect astroglial and neuronal damage after ETSS.

Topically applied mometasone furoate improves dysphagia in adult eosinophilic esophagitis - results from a double-blind, randomized, placebo-controlled trial.

OBJECTIVES: Topical corticosteroids are considered a cornerstone in the treatment of patients with eosinophilic esophagitis. The aim of this study was to evaluate the benefit of using mometasone furoate spray versus placebo on dysphagia and health-related quality of life in these patients. MATERIAL AND METHODS: Consecutive, newly diagnosed adult patients with eosinophilic esophagitis were randomized and treated with either 200 micrograms of orally administered topical mometasone furoate or placebo 4 times daily for 8 weeks. Symptoms and quality of life were evaluated using questionnaires including the Watson Dysphagia Scale, the European Organization for Research and Treatment of Cancer Quality of Life-Oesophageal Module 18 and the Short Form-36 before and after treatment. RESULTS: In the intention-to-treat analysis (n = 36) the Watson Dysphagia Scale score after mometasone treatment was reduced by 6.5 (median, p < .01) compared with 0 (median, ns) in the placebo group. The benefit of mometasone over placebo was significant (p < .05). In the per-protocol analysis (n = 33) the Watson Dysphagia Scale score was reduced by 5 (median, p = .01) after mometasone treatment compared with 0 (median, ns) in the placebo group. The advantage of mometasone over the placebo was significant (p < .05). The benefit of using mometasoneas evaluated by the two quality of life questionnaires was, however, insignificant. CONCLUSIONS: Our finding suggests that in adult patients with eosinophilic esophagitis, topical mometasone furoate exerts a beneficial effect compared with placebo regarding the main symptom, i.e., dysphagia. A corresponding benefit could not be verified regarding the various quality of life measurements. CLINICAL TRIAL REGISTRATION: Mometasone-furoate for Treatment of Eosinophilic Esophagitis - a Randomized Placebo Controlled Study ClinicalTrials.gov Identifier (NCT02113267).

Retrospective chart review: seasonal variation in incidence of bolus impaction is maintained and statistically significant in subgroups with atopy and eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition with eosinophilic infiltration of the esophageal mucosa. The most prominent symptom is dysphagia, which may result in esophageal bolus impaction in need of surgical extraction. To investigate whether an earlier reported seasonal variation in esophageal bolus impaction present only in a subgroup of patients with EoE and atopic disorders could be confirmed in this larger study. A single center retrospective chart review of patients who were diagnosed with esophageal bolus impaction between January 2004 and December 2017 was performed. Clinical, epidemiological and histologic data were collected. A total of 755 cases with esophageal bolus impaction were reviewed. A significantly higher occurrence of soft bolus impaction in summer and fall was shown in cases with confirmed EoE and in cases with atopy but not in the nonatopic group or in the group with a negative biopsy result. EoE was found in 48% of biopsied patients. A significant seasonal variation in cases with esophageal bolus impaction and concomitant atopy and EoE is confirmed, but the study design does not allow a causative role of allergens to be established.

The diagnostic value of GerdQ in subjects with atypical symptoms of gastro-esophageal reflux disease.

BACKGROUND: Symptoms are essential in the clinical diagnosis of gastro-esophageal reflux disease (GERD). Questionnaires such as GerdQ have been developed as diagnostic aids. GerdQ has been thoroughly validated in well-characterized GERD patients, but has not yet been fully evaluated in a population that includes subjects with atypical symptoms. AIM: To evaluate GerdQ in a population with typical and/or atypical symptoms of GERD, defined by 24-h pH monitoring. The secondary aim was to investigate the outcome of GerdQ depending on the response to proton pump inhibitor (PPI) treatment. METHODS: The study included 646 subjects referred for 24-h pH monitoring due to a clinical suspicion of GERD. All subjects completed GerdQ before performing a 24-h pH monitoring. RESULTS: In total, 377 (58%) subjects were diagnosed with GERD based on symptoms and 24-h pH monitoring (GERDpH). Of these, 46% had atypical main symptoms. Overall, GerdQ (at cut-off 8) predicted GERDpH with a sensitivity and specificity of 62% and 74%, respectively. A high specificity but poor sensitivity for diagnosis of GERDpH was found for atypical main symptoms such as cough, dysphagia and globus. GerdQ had a relatively high sensitivity and specificity in predicting PPI response and a PPV of 99% at cut-off 8. CONCLUSIONS: GerdQ has a diagnostic value in an unselected population presenting with typical and/or atypical symptoms of GERD, but a low sensitivity for diagnosis of GERDpH was found in subjects with predominant symptoms such as cough, dysphagia and globus.

The cultivable bacterial flora of the esophagus in subjects with esophagitis.

BACKGROUND: The healthy human esophagus is colonized by bacteria similar to that of the oral mucosa. However, little is known about the microbiome of the esophagus in esophagitis or the possible role of bacteria in the inflammatory response. AIM: To survey bacterial diversity and compare the microbiome of the esophagus in subjects with gastro-esophageal reflux disease (GERD) and eosinophilic esophagitis (EoE). MATERIAL AND METHODS: Seventeen subjects diagnosed with GERD and 10 with EoE underwent endoscopic examination with brush sampling and biopsies from the oral cavity, upper and lower esophagus. The samples were cultivated on agar plates, and bacterial growth was identified to the genus or species level and semi-quantified. RESULTS: Significantly higher numbers of bacterial groups or species were found in specimens from the lower esophagus in subjects with EoE compared to subjects with GERD (median 4 (range 1-7) vs. 2 (range 0-6), p < .0014). Sixteen vs. 14 different bacterial groups or species were found in subjects with GERD and EoE, respectively, mostly in sparse or very sparse amounts. Alfa-streptococci (viridans streptococci) were the most common bacteria in both groups. Streptococci were present in all of the EoE-subjects but only in approximately 75% in lower esophagus of the GERD-subjects, regardless of the sampling method. CONCLUSION: Subjects with GERD had significantly less bacterial diversity in both oral and esophageal samples than EoE-subjects. Whether this discrepancy might be explained by an effect on the protective mucosal biofilm by the acidic content of the reflux in subjects with GERD remains unclear.

Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging.

OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas, little is known about objective indices that may reveal risk of visual impairment caused by tumor growth that leads to compression of the anterior visual pathways. This study aimed to explore diffusion tensor imaging (DTI) as a means for objective assessment of injury to the anterior visual pathways caused by pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas, scheduled for transsphenoidal tumor resection, and 20 healthy control subjects were included in the study. A minimum suprasellar tumor extension of Grade 2-4, according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and posterior) scale, was required for inclusion. Neuroophthalmological examinations, conventional MRI, and DTI were completed in all subjects and were repeated 6 months after surgery. Quantitative assessment of chiasmal lift, visual field defect (VFD), and DTI parameters from the optic tracts was performed. Linear correlations, group comparisons, and prediction models were done in controls and patients. RESULTS Both the degree of VFD and chiasmal lift were significantly correlated with the radial diffusivity (r = 0.55, p < 0.05 and r = 0.48, p < 0.05, respectively) and the fractional anisotropy (r = -0.58, p < 0.05 and r = -0.47, p < 0.05, respectively) but not with the axial diffusivity. The axial diffusivity differed significantly between controls and patients with VFD, both before and after surgery (p < 0.05); however, no difference was found between patients with and without VFD. Based on the axial diffusivity and fractional anisotropy, a prediction model classified all patients with VFD correctly (sensitivity 1.0), 9 of 12 patients without VFD correctly (sensitivity 0.75), and 17 of 20 controls as controls (specificity 0.85). CONCLUSIONS DTI could detect pathology and degree of injury in the anterior visual pathways that were compressed by pituitary adenomas. The correlation between radial diffusivity and visual impairment may reflect a gradual demyelination in the visual pathways caused by an increased tumor effect. The low level of axial diffusivity found in the patient group may represent early atrophy in the visual pathways, detectable on DTI but not by conventional methods. DTI may provide objective data, detect early signs of injury, and be an additional diagnostic tool for determining indication for surgery in cases of pituitary adenomas.

Dysphagia and health-related quality of life in patients with eosinophilic esophagitis: a long-term follow-up.

Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated disease, with dysphagia as the main symptom. The aim of this study was to survey symptoms and health-related quality of life in adult patients with EoE at least 1 year after diagnosis and a 2-month course of topical corticosteroids. Forty-seven consecutive patients [79 % males, mean age 49 years (range 18-90 years)] were evaluated using three different questionnaires at three different occasions: the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Oesophageal Module 18 (EORTC QLQ-OES18) and the Short Form-36 (SF-36). The median time from diagnosis to the long-term follow-up was 23 months (range 12-34 months). The WDS scores and the EORTC QLQ-OES18 Dysphagia and Eating scale scores were improved after 2 months of treatment (p = 0.00007, p = 0.01, p = 0.004, respectively), as were the long-term follow-up scores (p = 0.01, p = 0.03, p = 0.005, respectively), relative to the scores at diagnosis. In addition, the EORTC QLQ-OES18 Choking scores were improved after the steroid course (p = 0.003) but not after the long-term follow-up. No significant differences were detected with respect to the SF-36 scores. In summary, EoE seems to be associated with a substantial burden of symptoms that improve significantly after treatment. A partial remission persists more than 1 year after diagnosis and the discontinuation of medication. The WDS and the EORTC QLQ-OES18 appear to be sensitive instruments appropriate for surveillance in these patients.

Topical corticosteroids do not revert the activated phenotype of eosinophils in eosinophilic esophagitis but decrease surface levels of CD18 resulting in diminished adherence to ICAM-1, ICAM-2, and endothelial cells.

Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.

Structured diagnostic and treatment approach versus the usual primary care approach in patients with gastroesophageal reflux disease: a cluster-randomized multicenter study.

GOALS: To compare the clinical outcomes of gastroesophageal reflux disease (GERD) patients treated with an implemented new structured pathway (NSP) or according to existing local clinical practices [old clinical pathway (OCP)]. BACKGROUND: GERD is a major challenge at the primary care level. STUDY: Primary care centers (n=24) were cluster randomized to handle patients suffering from symptoms suggestive of GERD according to the NSP (n=97) or the OCP (n=134). In the NSP, the GerdQ questionnaire score was used both for diagnosis and management including treatment. We used validated questionnaires to evaluate disease symptoms, quality of life, and costs at inclusion and at follow-up 2 to 6 months later. RESULTS: On the basis of the Reflux Disease Questionnaire, 56% of the patients treated with the NSP reported total symptom relief at the follow-up compared with 33% in the OCP group (P=0.0013). The reflux symptoms after treatment affected daily activities to a lesser extent in the patients in the NSP group compared with the OCP group (10% vs. 13%, respectively, P=0.01). The utility score of the EuroQoL-5D questionnaire improved more in the NSP group than in the OCP group (0.05 vs. 0.02, respectively, P<0.001). The patients in the NSP group had an approximately 50% lower average total cost for GERD-related health care resources compared with the OCP group [301 Swedish Kronor (SEK) vs. 588 SEK, respectively, NS]. CONCLUSIONS: The management of GERD patients in primary care centers using a structured clinical pathway and the results of the GerdQ improves the clinical outcome compared with prevailing local routines (NCT00842387).

Validation of the Swedish M. D. Anderson Dysphagia Inventory (MDADI) in patients with head and neck cancer and neurologic swallowing disturbances.

The aim of this study was to validate the Swedish version of the dysphagia-specific quality-of-life questionnaire, the M. D. Anderson Dysphagia Inventory (MDADI). Patients with oropharyngeal dysphagia due to neurologic disease (n = 30) and head and neck (H&N) cancer patients with post-treatment subjective dysphagia (n = 85) were compared to an age- and gender-matched nondysphagic control group (n = 115). A formal forward-backward translation was performed and followed international guidelines. Validity and reliability were tested against the Short-Form 36 (SF-36) and Hospital Anxiety and Depression Scale (HADS). Internal-consistency reliability was calculated by means of Cronbach's α coefficient. Test-retest reliability was assessed by intraclass correlation (ICC). Convergent and discriminant validity were assessed by correlations between MDADI, SF-36, and HADS. Known-group validity was examined and statistically tested. Of 126 eligible patients, 115 agreed to participate (response rate = 91.3%). The age of the participants ranged between 37 and 92 years. Most of the MDADI items showed good variability and only minor floor or ceiling effects in solitary items were found. The internal-consistency reliability (Cronbach's α) of the MDADI total score was 0.88 (after correction for systematic errors in the subjects' responses to two reversed questions). All estimates reached over the satisfactory >0.70 reliability standard for group-level comparison. ICC ranged between 0.83 and 0.97 in the test-retest. The mean MDADI total score was 66.9 (SD = 14.7) for the H&N cancer patients, 65.0 (16.9) for the neurologic patients, and 97.5 (4.4) for the control group (P < 0.001; study patients vs. controls). The MDADI was also sensitive to disease severity as measured by different food textures. The Swedish version of the MDADI showed good psychometric properties and is a valid instrument to assess dysphagia-related quality of life. It was also shown to be a reliable instrument after correction for systematic errors in the subjects' responses to two reversed questions. Its known-group validity enables the differentiation between dysphagic and nondysphagic patients for group-level research.

Distinctive blood eosinophilic phenotypes and cytokine patterns in eosinophilic esophagitis, inflammatory bowel disease and airway allergy.

Blood eosinophil numbers may be elevated in allergy, inflammatory bowel disease and eosinophilic esophagitis. The aim of this study was to examine whether circulating eosinophils display distinct phenotypes in these disorders and if different patterns of eosinophilic chemoattractants exist. Blood eosinophils from patients with symptomatic eosinophilic esophagitis (EoE; n = 12), ulcerative colitis (n = 8), airway allergy (n = 10) and healthy controls (n = 10) were enumerated and their surface markers analyzed by flow cytometry. Plasma levels of pro-eosinophilic cytokines were quantified in parallel. Data were processed by multivariate pattern recognition methods to reveal disease-specific patterns of eosinophil phenotypes and cytokines. EoE patients had higher numbers of eosinophils with enhanced expression of CD23, CD54, CRTH2 and CD11c and diminished CCR3 and CD44 expression. Plasma CCL5 was also increased in EoE. Although allergic patients had increased interleukin (IL)-2, IL-3, IL-5 and granulocyte macrophage colony-stimulating factor plasma concentrations, their blood eosinophil phenotypes were indistinguishable from those of healthy controls. Decreased eosinophilic expression of CD11b, CD18, CD44 and CCR3, but no distinctive pattern of eosinophil chemoattractants, characterized ulcerative colitis. We propose that eosinophils acquire varying functional properties as a consequence of distinct patterns of activation signals released from the inflamed tissues in different diseases.