Odynophagia and Retrosternal Pain Are Common in Eosinophilic Esophagitis and Associated with an Increased Overall Symptom Severity.

BACKGROUND AND AIMS: Dysphagia is the hallmark symptom in eosinophilic esophagitis (EoE). However, data are limited regarding the overall prevalence and potential implications of atypical symptoms like odynophagia and retrosternal pain. METHODS: Patients enrolled into the Swiss EoE cohort study (SEECS) were analyzed regarding the presence of odynophagia and retrosternal pain. Demographics, other EoE-related symptoms, histologic and endoscopic activity were compared between EoE-patients with vs. without odynophagia and/or retrosternal pain. RESULTS: 474 patients (75.2% male) were analyzed. In their individual course of disease 110 (23.2%) patients stated to have ever experienced odynophagia and 64 (13.5%) retrosternal pain independent of food intake, 24 (5%) patients complained about both symptoms. Patients with odynophagia consistently scored higher in symptom severity (p < 0.001), EREFS score (median 3.0 vs. 2.0, p = 0.006), histologic activity and a lower quality of life (p = 0.001) compared to patients without odynophagia. Sex, age at diagnosis, EoE-specific treatment, complications such as candida or viral esophagitis and disease duration were similar in patients with vs. without odynophagia. Also patients with retrosternal pain scored higher in symptom severity (2.0 vs. 1.0, p = 0.001 and 2.0 vs. 1.0, p < 0.001 in physician and patient questionnaire assessment, respectively). However, there was neither a difference in endoscopic/histologic disease activity nor in quality of life according to presence or absence of retrosternal pain. Due to logistic reasons, a stratification regarding the presence of concomitant dysphagia was not possible. CONCLUSION: Odynophagia and swallowing-independent retrosternal pain are common symptoms in patients with EoE, associate with an overall higher EoE-related symptom severity and for the case of odynophagia lower quality of life. However, the influence of concomitant dysphagia and its severity remains unclear and needs to be included in future analyses.

Evaluation of soluble suppression of tumorigenicity 2 (sST2) as serum marker for liver fibrosis.

BACKGROUND & AIMS: With the increase in patients at risk of advanced liver disease due to the obesity epidemic, there will be a need for simple screening tools for advanced liver fibrosis. Soluble suppression of tumorigenicity 2 (sST2) is a serum biomarker for fibrotic processes. The aim of this study was to evaluate sST2 as marker for liver fibrosis in patients successfully treated for chronic hepatitis C. METHODS: 424 patients from the Swiss Hepatitis C Cohort Study were screened for inclusion in this post-hoc cohort study. Inclusion criteria were sustained virological response (SVR), available elastography (VCTE) and serum samples for biomarker analysis before and after treatment. For the validation of sST2, values were compared to VCTE, FIB-4 and APRI using Spearman's correlation and AUROC analyses. RESULTS: Data of 164 subjects were finally analyzed. Median sST2 values slightly increased with VCTE-derived fibrosis stages and remained stable after reaching SVR within the respective fibrosis stage, suggesting that sST2 is not influenced by liver inflammation. However, correlation of sST2 pre- and post-treatment with VCTE was fair (Spearman's rho = 0.39 and rho = 0.36). The area under the curve (AUROC) for sST2 in detecting VCTE-defined F4 fibrosis (vs. F0-F3) before therapy was 0.74 (95%CI 0.65-0.83), and 0.67(95%CI 0.56-0.78) for the discrimination of F3/F4 fibrosis vs. F0-F2. Adding sST2 to either APRI or FIB-4, respectively, increased diagnostic performance of both tests. CONCLUSIONS: sST2 can potentially identify patients with advanced fibrosis as a single serum marker and in combination with APRI and FIB-4.

Sex-specific clinical characteristics and treatment responses in delirium management: findings from a prospective cohort study in elderly patients.

Delirium incidence and phenotype differ between sexes. Sex differences in the selection of treatment strategies remain elusive. We evaluated sex-specific responses to non- and pharmacological management. In this observational prospective cohort study conducted at the University Hospital Zurich, Switzerland, 602 patients managed for delirium were analyzed. Remission and benefit ratios of treatments were calculated using Cox regression models. Baseline characteristics were similar in both sexes. Overall, 89% of all patients (540/602) received pharmacological management for delirium, most (77%) with one or two different medications. An equal number of male and female patients had either no medication ( P  = 0.321) or three and more medications ( P  = 0.797). Men had two different medications more often ( P  = 0.009), while women more frequently received one medication ( P  = 0.037). Remission rates within 20 days were higher in non-pharmacological treatment and similar between sexes, with odds of 1.36 in females, and 2.3 in males. Non-pharmacological treatment was equally efficacious in both sexes. Women who received supportive treatment and monotherapy had equal odds of remission. Men fared better with supportive care compared to pharmacologic therapies. Remission rates with different management strategies were similar between sexes. No sex differences were found regarding phenotypes, clinical course, and response to therapy.

Predisposing and precipitating risk factors for delirium in gastroenterology and hepatology: Subgroup analysis of 718 patients from a hospital-wide prospective cohort study.

Background and Aims: Delirium is the most common acute neuropsychiatric syndrome in hospitalized patients. Higher age and cognitive impairment are known predisposing risk factors in general hospital populations. However, the interrelation with precipitating gastrointestinal (GI) and hepato-pancreato-biliary (HPB) diseases remains to be determined. Patients and methods: Prospective 1-year hospital-wide cohort study in 29'278 adults, subgroup analysis in 718 patients hospitalized with GI/HPB disease. Delirium based on routine admission screening and a DSM-5 based construct. Regression analyses used to evaluate clinical characteristics of delirious patients. Results: Delirium was detected in 24.8% (178/718). Age in delirious patients (median 62 years [IQR 21]) was not different to non-delirious (median 60 years [IQR 22]), p = 0.45). Dementia was the strongest predisposing factor for delirium (OR 66.16 [6.31-693.83], p < 0.001). Functional impairment, and at most, immobility increased odds for delirium (OR 7.78 [3.84-15.77], p < 0.001). Patients with delirium had higher in-hospital mortality rates (18%; OR 39.23 [11.85-129.93], p < 0.001). From GI and HPB conditions, cirrhosis predisposed to delirium (OR 2.11 [1.11-4.03], p = 0.023), while acute renal failure (OR 4.45 [1.61-12.26], p = 0.004) and liver disease (OR 2.22 [1.12-4.42], p = 0.023) were precipitators. Total costs were higher in patients with delirium (USD 30003 vs. 10977; p < 0.001). Conclusion: Delirium in GI- and HPB-disease was not associated with higher age per se, but with cognitive and functional impairment. Delirium needs to be considered in younger adults with acute renal failure and/or liver disease. Clinicians should be aware about individual risk profiles, apply preventive and supportive strategies early, which may improve outcomes and lower costs.

Corrigendum: Risk Factors for Delirium Are Different in the Very Old: A Comparative One-Year Prospective Cohort Study of 5,831 Patients.

[This corrects the article DOI: 10.3389/fpsyt.2021.655087.].

Clinical parameters associated with gastric portal hypertensive polyps.

OBJECTIVES: Portal hypertensive polyps (PHPs) are incompletely characterized lesions that can be found in the distal stomach of patients with portal hypertension. We aimed to delineate clinical factors associated with the appearance of these rare polyps. MATERIAL AND METHODS: We conducted a cross-sectional study of a cohort with 513 cirrhotic patients comparing patients with and without PHP using descriptive analyses and multivariable logistic regression. To address the problem of missing values, in particular for HVPG and liver stiffness, we used multiple imputation of missing values. RESULTS: The prevalence of macroscopically diagnosed PHP was 3.3% (95% confidence interval 2.0 - 5.4%). In 53% of cases, the correct classification was missed on index gastroscopy. Patients with PHP were older at gastroscopy (65 years vs. 59), had higher hepatic venous pressure gradients (HVPG, 28 mmHg vs. 19 mmHg), higher transient elastography (TE) measurements (50.7 kPa vs. 21.8 kPa) and more often had previous rubber band ligations (RBL, 64.7% vs. 25.8%). The multivariable logistic regression on the outcome macroscopically diagnosed PHP estimated an odds ratio (OR) for HPVG of 1.13 (CI 0.95-1.34), increased liver stiffness of 1.03 (1.00 - 1.07) and previous RBL of 3.84 (1.24 - 11.88), respectively. CONCLUSION: The prevalence of PHPs in the stomach was higher than assumed in previous studies and misclassification was commonly observed. The appearance of these rare polyps is associated with previous RBL and may correlate with severity of PH. Thus, PHPs may be regarded as marker for relevant PH, but clinical significance of these polyps is still uncertain.

Discharge Destinations of Delirious Patients: Findings From a Prospective Cohort Study of 27,026 Patients From a Large Health Care System.

OBJECTIVES: Delirium is known to contribute to increased rates of institutionalization and mortality. The full extent of adverse outcomes, however, remains understudied. We aimed to systematically assess the discharge destinations and mortality risk in delirious patients in a large sample across all hospital services. DESIGN: Pragmatic prospective cohort study of consecutive admissions to a large health care system. SETTING AND PARTICIPANTS: A total of 27,026 consecutive adults (>18 years old) with length of stay of at least 24 hours in a tertiary care center from January 1 to December 31, 2014. METHODS: Presence of delirium determined by routine delirium screening. Clinical characteristics, discharge destination, and mortality were collected. Calculation of odds ratios (ORs) with logistic regression with adjustment for age, sex, and Charlson comorbidity index (CCI). RESULTS: Delirium was detected in 19.7% of patients (5313 of 27,026), median age of delirious patients was 56 years (25-75 interquartile range = 37-70). The electronic health record (DSM-5-based) delirium algorithm correctly identified 93.3% of delirium diagnoses made by consultation-liaison psychiatrists. Across services, the odds of delirious patients returning home was significantly reduced [OR 0.12; confidence interval (CI) 0.10-0.13; P < .001]. Rather, these patients were transferred to acute rehabilitation (OR 4.15; CI 3.78-4.55; P < .001) or nursing homes (OR 4.12; CI 3.45-4.93; P < .001). Delirious patients had a significantly increased adjusted mortality risk (OR 30.0; CI 23.2-39.4; P < .001). CONCLUSIONS AND IMPLICATIONS: This study advances our understanding of the discharge destination across all services in adults admitted to a large hospital system. Delirium was associated with reduced odds of returning home, increased odds of discharge to a setting of higher dependency, and excess mortality independent of comorbidity, age, and sex. These findings emphasize the potentially devastating outcomes associated with delirium and highlight the need for timely diagnosis and hospital-wide management.

Delirium in trauma patients: a 1-year prospective cohort study of 2026 patients.

BACKGROUND: Delirium in trauma surgery is common, especially post-operatively, but medical characteristics, risk factors and residence post-discharge have not comprehensively been investigated in all trauma patients. METHODS: Over 1 year, 2026 trauma patients were prospectively screened for delirium with the following tools: Delirium Observation screening scale (DOS), Intensive Care Delirium Screening Checklist (ICDSC) and a DSM (Diagnostic and Statistical Manual)-5, nursing tool (ePA-AC) construct. Risk factors-predisposing und precipitating-for delirium were assessed via multiple regression analysis. RESULTS: Of 2026 trauma patients, 440 (21.7%) developed delirium, which was associated with an increased risk of assisted living (OR 6.42, CI 3.92-10.49), transfer to nursing home (OR 4.66, CI 3.29-6.6), rehabilitation (OR 3.96, CI 3.1-5.1), or death (OR 70.72, CI 22-227.64). Intensive care management (OR 18.62, CI 14.04-24.68), requirement of ventilation (OR 32.21, CI 21.27-48.78), or its duration (OR 67.22, CI 33.8-133.71) all increased the risk for developing delirium. Relevant predisposing risk factors were dementia (OR 50.92, CI 15.12-171.45), cardiac insufficiency (OR 11.76, CI 3.6-38.36), and polypharmacy (OR 5.9, CI 4.01-8.68).Relevant precipitating risk factors were brain edema (OR 40.53, CI 4.81-341.31), pneumonia (OR 39.66, CI 8.89-176.93) and cerebral inflammation (OR 21.74, CI 2.34-202.07). CONCLUSION: Delirium in trauma patients is associated with poor outcome as well as with intensive care management and various predisposing and/or precipitating factors. Three quarters of patients who had undergone delirium were not able to live independently at home any more.

Predisposing and Precipitating Risk Factors for Delirium in Elderly Patients Admitted to a Cardiology Ward: An Observational Cohort Study in 1,042 Patients.

Aim: Although the risk factors for delirium in general medicine are well-established, their significance in cardiac diseases remains to be determined. Therefore, we evaluated the predisposing and precipitating risk factors in patients hospitalized with acute and chronic heart disease. Methods and Results: In this observational cohort study, 1,042 elderly patients (≥65 years) admitted to cardiology wards, 167 with and 875 without delirium, were included. The relevant sociodemographic and cardiac- and medical-related clusters were assessed by simple and multiple regression analyses and prediction models evaluating their association with delirium. The prevalence of delirium was 16.0%. The delirious patients were older (mean 80 vs. 76 years; p < 0.001) and more often institutionalized prior to admission (3.6 vs. 1.4%, p = 0.05), hospitalized twice as long (12 ± 10 days vs. 7 ± 7 days; p < 0.001), and discharged more often to nursing homes (4.8 vs. 0.6%, p < 0.001) or deceased (OR, 2.99; 95% CI, 1.53-5.85; p = 0.003). The most relevant risk factor was dementia (OR, 18.11; 95% CI, 5.77-56.83; p < 0.001), followed by history of stroke (OR, 6.61; 95% CI 1.35-32.44; p = 0.020), and pressure ulcers (OR, 3.62; 95% CI, 1.06-12.35; p = 0.040). The predicted probability for developing delirium was highest in patients with reduced mobility and institutionalization prior to admission (PP = 31.2%, p = 0.001). Of the cardiac diseases, only valvular heart disease (OR, 1.57; 95% CI, 1.01-2.44; p = 0.044) significantly predicted delirium. The patients undergoing cardiac interventions did not have higher rates of delirium (OR, 1.39; 95% CI 0.91-2.12; p = 0.124). Conclusion: In patients admitted to a cardiology ward, age-related functional and cognitive impairment, history of stroke, and pressure ulcers were the most relevant risk factors for delirium. With regards to specific cardiological factors, only valvular heart disease was associated with risk for delirium. Knowing these factors can help cardiologists to facilitate the early detection and management of delirium.

Risk Factors for Delirium Are Different in the Very Old: A Comparative One-Year Prospective Cohort Study of 5,831 Patients.

Background: In an ever-aging society, health care systems will be confronted with an increasing number of patients over 80 years ("the very old"). Currently, knowledge about and recommendations for delirium management are often based on studies in patients aged 60 to 65 years. It is not clear whether these findings apply to patients ≥80 years. Aim: Comparison of younger and older patients with delirium, especially regarding risk factors. Methods: In this prospective cohort study, within 1-year, 5,831 patients (18-80 years: n = 4,730; ≥80: n = 1,101) with delirium were enrolled. The diagnosis of delirium was based on the Delirium Observation screening scale (DOS), Intensive Care Delirium Screening Checklist (ICDSC) and a DSM (Diagnostic and Statistical Manual)-5 construct of nursing instrument. Sociodemographic trajectories, as well as the relevant predisposing and precipitating factors for delirium, were assessed via a multiple regression analysis. Results: The very old were more commonly admitted as emergencies (OR 1.42), had a greater mortality risk (OR 1.56) and displayed fewer precipitating risk factors for the development of a delirium, although the number of diagnoses were not different (p = 0.325). Predisposing factors were sufficient almost alone for the development of delirium in patients ≥ 80 years of age; in 18-80 years of age, additional precipitating factors had to occur to make a delirium possible. Conclusion: When relevant predisposing factors for delirium are apparent, patients over 80 years of age require comparatively few or no precipitating factors to develop delirium. This finding should be taken into account at hospitalization and may allow better treatment of delirium in the future.

Pyloric dilation with the esophageal functional lumen imaging probe in gastroparesis improves gastric emptying, pyloric distensibility, and symptoms.

BACKGROUND AND AIMS: The role of decreased pyloric distensibility in gastroparesis as measured by the endolumenal functional luminal imaging probe (EndoFLIP) has been receiving increasing attention. In this study, we present clinical outcomes to pyloric dilation with the esophageal FLIP (EsoFLIP) in regard to gastric emptying, symptom evolution, and FLIP metrics. METHODS: Patients evaluated for gastroparesis (gastric emptying studies of t1/2 ≥180 minutes during 13C-octanoic acid breath test and/or gastric remnants during gastroscopy after a sufficient fasting period) were scheduled for EsoFLIP controlled pyloric dilation. Pre- and postprocedural gastric emptying studies, questionnaires (Patient Assessment of Upper GI Symptoms Severity Index [PAGI-SYM; including the Gastroparesis Cardinal Symptom Index] and Patient Assessment of Quality of Life Index [PAGI-QOL]), and FLIP metrics were documented. Dilation was conducted according to a self-developed algorithm. RESULTS: Forty-six patients were analyzed (72% women; median age, 39 years [range, 18-88]). Etiologies of gastroparesis were diabetic in 10 patients (22%), idiopathic in 33 (72%), and postoperative in 3 (6%). Postprocedural gastric emptying time decreased from a median of 211 minutes to 179 minutes (P = .001). In accordance, pyloric distensibility, PAGI-SYM, PAGI-QOL, and Gastroparesis Cardinal Symptom Index values improved significantly. After a median follow-up of 3.9 months, 57% of all treated patients with returned questionnaires reported improved symptoms. CONCLUSIONS: Pyloric EsoFLIP controlled dilation shows value in the treatment of gastroparesis, both subjectively and objectively. Long-term follow-up to assess efficacy and comparative trials are warranted.

Heart rate elevations during early sepsis predict death in fluid-resuscitated rats with fecal peritonitis.

BACKGROUND: In sepsis, early outcome prediction would allow investigation of both adaptive mechanisms underlying survival and maladaptive mechanisms resulting in death. The aim of this study was to test whether early changes in heart rate monitored by telemetry could predict outcome in a long-term rat model of fecal peritonitis. METHODS: Male Wistar rats (n = 24) were instrumented with a central venous line for administration of fluids, antibiotics and analgesics. A telemetry transmitter continuously collected electrocardiogram signals. Sepsis was induced by intraperitoneal injection of fecal slurry, and the animals were observed for 48 h. Additional animals underwent arterial cannulation at baseline (n = 9), 4 h (n = 16), or 24 h (n = 6) for physiology and laboratory measurements. RESULTS: 48-h mortality was 33% (8/24), with all deaths occurring between 4 and 22 h. Septic animals were characterized by lethargy, fever, tachycardia, positive blood cultures, and elevated cytokine (IL-1, IL-6, TNF alpha) levels. An increase in heart rate ≥ 50 bpm during the first 4 h of sepsis predicted death with sensitivity and specificity of 88% (p = 0.001). CONCLUSIONS: In this long-term rat sepsis model, prognostication could be made early by telemetry-monitored changes in heart rate. This model enables the study of underlying mechanisms and the assessment of any differential effects of novel therapies in predicted survivors or non-survivors.

Improving animal welfare using continuous nalbuphine infusion in a long-term rat model of sepsis.

BACKGROUND: Sepsis research relies on animal models to investigate the mechanisms of the dysregulated host response to infection. Animal welfare concerns request the use of potent analgesics for the Refinement of existing sepsis models, according to the 3Rs principle. Nevertheless, adequate analgesia is often missing, partly because the effects of analgesics in this particular condition are unknown. We evaluated the use of nalbuphine, an opioid with kappa agonistic and mu antagonistic effects, in rats with and without experimental sepsis. METHODS: Male Wistar rats were anesthetized with isoflurane and instrumented with a venous line for drug administration. Arterial cannulation allowed for blood pressure measurements and blood sampling in short-term experiments of non-septic animals. Nalbuphine (or placebo) was administered intravenously at a dose of 1 mg/kg/h. Long-term (48 h) experiments in awake septic animals included repetitive clinical scoring with the Rat Grimace Scale and continuous heart rate monitoring by telemetry. Sepsis was induced by intraperitoneal injection of faecal slurry. Nalbuphine plasma levels were measured by liquid chromatography-high resolution mass spectrometry. RESULTS: In anesthetized healthy animals, nalbuphine led to a significant reduction of respiratory rate, heart rate, and mean arterial pressure during short-term experiments. In awake septic animals, a continuous nalbuphine infusion did not affect heart rate but significantly improved the values of the Rat Grimace Scale. Nalbuphine plasma concentrations remained stable between 4 and 24 h of continuous infusion in septic rats. CONCLUSIONS: In anaesthetised rats, nalbuphine depresses respiratory rate, heart rate, and blood pressure. In awake animals, nalbuphine analgesia improves animal welfare during sepsis.

The multimorbidity interaction severity index (MISI): A proof of concept study.

Therapeutic decision-making for patients with multimorbidity (MM) is challenging. Clinical practice guidelines inadequately address harmful interactions and resulting therapeutic conflicts within and among diseases. A patient-specific measure of MM severity that takes account of this conflict is needed.As a proof of concept, we evaluated whether the new Multimorbidity Interaction Severity Index (MISI) could be used to reliably differentiate patients in terms of lower versus higher potential for harmful interactions.Two hypothetical patient cases were generated, each with 6 concurrent morbidities. One case had a low (i.e., low conflict case) and the other a high (i.e., high conflict case) potential for harmful interactions. All possible interactions between conditions and treatments were extracted from each case's record into a multimorbidity interaction matrix. Experienced general internists (N = 18) judged each interaction in the matrix in terms of likely resource utilization needed to manage the interaction. Based on these judgements, a composite index of MM interaction severity, that is, the MISI, was generated for each physician and case.The difference between each physician's MISI score for the 2 cases (MISIdiff) was computed. Based on MISIdiff, the high conflict case was judged to be of significantly greater MM severity than was the low conflict case. The positive values of the inter-quartile range, a measure of variation (or disagreement) between the 2 cases, indicated general consistency of individual physicians in judging MM severity.The data indicate that the MISI can be used to reliably differentiate hypothetical multimorbid patients in terms of lesser versus greater severity of potentially harmful interactive effects. On this basis, the MISI will be further developed for use in patient-specific assessment and management of MM. The clinical relevance of the MISI as an alternative approach to defining MM severity is discussed.

Disease-Targeted Treatment Improves Cognitive Function in Patients with Precapillary Pulmonary Hypertension.

BACKGROUND: Patients with pulmonary hypertension (PH) may suffer from cognitive deficits that potentially relate to reduced oxygen delivery and cerebral tissue oxygenation (CTO). OBJECTIVE: To evaluate the hypothesis that cognitive function improves with therapy, along with improved CTO. METHODS: Twenty incident patients with arterial or chronic thromboembolic PH had CTO monitoring by near-infrared spectroscopy during diagnostic right heart catheterization. Cognitive tests [Trail Making Tests (TMTs), Victoria Stroop tests and the Five-Point Test (5PT)], the 6-min walk distance (6MWD) test, New York Heart Association (NYHA) class and health-related quality of life (HRQoL) were assessed and repeated after 3 months of disease-targeted medication. RESULTS: At baseline, 45% of PH patients had cognitive deficits. At 3 months, the patients had improved on the TMT A and the Stroop 2 test [37 s (27; 55) versus 30 s (24; 42), p < 0.05, and 18 s (16; 22) versus 16 s (15; 20), p < 0.01], whereas CTO remained unchanged. Arterial oxygen saturation, NYHA class, 6MWD and HRQoL had also improved. Baseline CTO was the strongest predictor of cognitive function, even in multivariate analysis including age, 6MWD and HRQoL. Improvements in cognitive function were not associated with changes in CTO. CONCLUSIONS: In patients with PH, 3 months of disease-targeted medication resulted in better cognitive function. Although CTO was the strongest predictor of cognitive function at baseline, it did not change during target therapy. The results of this pilot study should be confirmed in an adequately powered controlled trial.

Effect of nocturnal oxygen and acetazolamide on exercise performance in patients with pre-capillary pulmonary hypertension and sleep-disturbed breathing: randomized, double-blind, cross-over trial.

AIM: Sleep-disturbed breathing (SDB) is common in pre-capillary pulmonary hypertension (PH) and impairs daytime performance. In lack of proven effective treatments, we tested whether nocturnal oxygen therapy (NOT) or acetazolamide improve exercise performance and quality of life in patients with pre-capillary PH and SDB. METHODS: This was a randomized, placebo-controlled, double-blind, three period cross-over trial. Participants received NOT (3 L/min), acetazolamide tablets (2 × 250 mg), and sham-NOT/placebo tablets each during 1 week with 1-week washout between treatment periods. Twenty-three patients, 16 with pulmonary arterial PH, 7 with chronic thromboembolic PH, and with SDB defined as mean nocturnal oxygen saturation <90% or oxygen saturation dips >10 h(-1) with daytime PaO2 ≥7.3 kPa participated. Assessments at the end of the treatment periods included a 6 min walk distance (MWD), SF-36 quality of life, polysomnography, and echocardiography. RESULTS: Medians (quartiles) of the 6 MWD after NOT, acetazolamide, and placebo were 480 m (390;528), 440 m (368;468), and 454 m (367;510), respectively, mean differences: NOT vs. placebo +25 m (95% CI 3-46, P= 0.027), acetazolamide vs. placebo -9 m (-34-17, P = 0.223), and NOT vs. acetazolamide +33 (12-45, P < 0.001). SF-36 quality of life was similar with all treatments. Nocturnal oxygen saturation significantly improved with both NOT and acetazolamide. Right ventricular fractional area change was greater on NOT compared with placebo (P = 0.042) and acetazolamide (P = 0.027). CONCLUSIONS: In patients with pre-capillary PH and SDB on optimized pharmacological therapy, NOT improved the 6 MWD compared with placebo already after 1 week along with improvements in SDB and haemodynamics. CLINICALTRIALSGOV: NTC01427192.

Effects of exercise and vasodilators on cerebral tissue oxygenation in pulmonary hypertension.

BACKGROUND: Arterial and thromboembolic pulmonary hypertension (PH) lead to arterial hypoxaemia. OBJECTIVE: To investigate whether cerebral tissue oxygenation (CTO) in patients with PH is reduced and whether this is associated with reduced exercise tolerance. METHODS: 16 patients with PH (mean pulmonary arterial pressure ≥25 mmHg, 14 arterial, 2 chronic thromboembolic) and 15 controls underwent right heart catheterisation with monitoring of CTO at rest, during maximal bicycle exercise and during inhalation of oxygen and NO. The 6 min walk distance (6MWD) was measured. RESULTS: Median CTO in PH-patients at rest was 62 % (quartiles 53; 71), during exercise 60 % (53; 65); corresponding values in controls were 65 % (73; 73) (P = NS) and 68 % (66; 70) (p = .013 vs. PH). Inhalation of NO and oxygen improved CTO in PH. In multivariate regression analysis CTO at maximal exercise predicted the work load achieved when controlled for age, pulmonary vascular resistance and mixed venous oxygen saturation (R (2) = .419, p < .000); in addition, the 6MWD was predicted by CTO (adjusted R (2) = .511, p < .000). CONCLUSION: In PH-patients but not in controls CTO decreased during exercise. Since CTO was an independent predictor of the work load achieved and the 6MWD cerebral hypoxia may contribute to exercise limitation in PH. Clinicaltrials.gov: NCT01463514.