Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial.

BACKGROUND & AIMS: Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD), and only limited treatment options are available. Based on the hypothetical link between low serum tryptophan concentrations and fatigue, we determined the effect of 5-hydroxytryptophan supplementation on fatigue in patients with inactive IBD. METHODS: A multicenter randomized controlled trial was performed at 13 Belgian hospitals, including 166 patients with IBD in remission but experiencing fatigue, defined by a fatigue visual analog scale (fVAS) score of ≥5. Patients were treated in a crossover manner with 100 mg oral 5-hydroxytryptophan or placebo twice daily for 2 consecutive periods of 8 weeks. The primary end point was the proportion of patients reaching a ≥20% reduction in fVAS after 8 weeks of intervention. Secondary outcomes included changes in serum tryptophan metabolites, Functional Assessment of Chronic Illness Therapy Fatigue scale, and scores for depression, anxiety, and stress. The effect of the intervention on the outcomes was evaluated by linear mixed modeling. RESULTS: During 5-hydroxytryptophan treatment, a significant increase in serum 5-hydroxytryptophan (estimated mean difference, 52.66 ng/mL; 95% confidence interval [CI], 39.34-65.98 ng/mL; P < .001) and serotonin (3.0 ng/mL; 95 CI, 1.97-4.03 ng/mL; P < .001) levels was observed compared with placebo. The proportion of patients reaching ≥20% reduction in fVAS was similar in placebo- (37.6%) and 5-hydroxytryptophan (35.6%)-treated patients (P = .830). The fVAS reduction (-0.18; 95% CI, -0.81 to 0.46; P = .581) and Functional Assessment of Chronic Illness Therapy Fatigue scale increase (0.68; 95% CI, -2.37 to 3.73; P = .660) were both comparable between 5-hydroxytryptophan and placebo treatment as well as changes in depression, anxiety, and stress scores. CONCLUSIONS: Despite a significant increase in serum 5-hydroxytryptophan and serotonin levels, oral 5-hydroxytryptophan did not modulate IBD-related fatigue better than placebo. (Trial Registration: Belgian Federal Agency for Medication and Health Products, EudraCT number: 2017-005059-10 and ClinicalTrials.gov: NCT03574948, https://clinicaltrials.gov/ct2/show/NCT03574948.).

An unusual cause of "traumatic" hemothorax: perforation of the lung parenchyma by a bifid rib.

Congenital anomalies of the ribs are relatively common, and they can be divided in numerical (for example cervical ribs) or structural abnormalities (for example bifid ribs). These anomalies are usually asymptomatic. Literature on symptomatic bifid ribs is limited. We present the case of a 36-year old male without any relevant medical history or medication who was referred to our center. After lifting a heavy object, he experienced sudden onset pain on the right anterior chest, with associated shortness of breath. Computed tomography of the chest showed a significant hemothorax on the right side, compression atelectasis of the right lower lobe, and an anomalous fifth right rib - described as a bifid rib. A VATS resection of the bifid rib was performed.The images of this case illustrate the unusual traumatic perforation of the lung caused by a bifid rib. The case illustrates that one might consider resection of an asymptomatic bifid rib when imaging suggests significant compression on the lung parenchyma.

Prognostic value of serum galactomannan in mixed ICU patients: a retrospective observational study.

BACKGROUND: Little is known about serum galactomannan (GM) testing in (mostly non-neutropenic) mixed intensive care unit (ICU) patients. The aim of this study was to look for the incidence of invasive aspergillosis (IA) in critically ill patients, to validate previously reported GM thresholds, and to evaluate the prognostic value of GM. METHODS: This was a retrospective study of 474 GM samples in 160 patients from the start of January 2003 until the start of February 2004. GM tests were ordered because of a clinical suspicion of IA or on a regular basis in immune compromised patients. The number of samples per patient was 3 ± 2.6. We used the criteria of the European Organisation for Research and Treatment of Cancer (EORTC) to define proven IA, probable IA, and possible IA. The number of positive samples, with GM optical density (OD) > 0.5 was 230 (48.5%). RESULTS: In our study population, five (3%) patients had proven IA, 11 (7%) had probable, 27 (17.5%) had possible, and 116 (72.5%) had no IA. We could not identify a GM threshold for IA with analysis of receiver operating characteristics (ROC) curves: with a sensitivity of (56.3%, 50%, 50%, 37.5%), specificity (38.2%, 67.5%, 68.8%, 72.9%), NPV (88.7%, 91.8%, 92.5%, 91.3%) and PPV (9.2%, 12.9%, 15.1%, 13.3%) for a cut-off of OD > 0.5, > 0.8, > 1.1 and > 1.5 respectively. IA was associated with high mortality of 87.5% and 100% in patients with probable and proven IA respectively. Patients with IA had a significant increase of GM during their stay (GMdelta 0.7 ± 1.5 vs -0.2 ± 1.5, P = 0.027). The overall ICU mortality was 41.9% and the hospital mortality was 58.1%. Patients who died in the ICU and in the hospital had higher APACHE- -II, SAPS-II and SOFA scores (P < 0.0001) and also a significant increase in GM during their stay with 0.27 ± 1.26 (ICU non-survivors) and 0.11 ± 1.55 (hospital non-survivors) compared to a decrease in GM -0.43 ± 1.7 (P = 0.004) and -0.48 ± 1.51 (P = 0.017) in ICU and hospital survivors respectively. Non-survivors also had higher mean GM values but this was not statistically significant. There was a trend towards higher GM values in patients treated with piperacillin/tazobactam (n = 34), but this did not reach statistical significance. Neutropenic patients (n = 31) showed an increase in GM during their stay 0.32 ± 1.3 vs a decrease with -0.43 ± 1.7 in non-neutropenic patients (P = 0.07). Patients on total parenteral nutrition (n = 125) had higher maximal GM levels (1.55 ± 1.94 vs 0.88 ± 1.25, P = 0.058). Patients who were mechanically ventilated had significantly higher mean (P = 0.038) and maximal (P = 0.007) GM levels. CONCLUSIONS: We found a high incidence of proven and probable IA in a group of mixed ICU patients (10%) and the presence of IA was associated with a high mortality. The serum GM antigen detection test may not be useful in the diagnosis of IA in mixed ICU patients, according to the results of the ROC analysis. We could not define a useful threshold.

Computer quantification of airway collapse on forced expiration to predict the presence of emphysema.

BACKGROUND: Spirometric parameters are the mainstay for diagnosis of COPD, but cannot distinguish airway obstruction from emphysema. We aimed to develop a computer model that quantifies airway collapse on forced expiratory flow-volume loops. We then explored and validated the relationship of airway collapse with computed tomography (CT) diagnosed emphysema in two large independent cohorts. METHODS: A computer model was developed in 513 Caucasian individuals with ≥15 pack-years who performed spirometry, diffusion capacity and CT scans to quantify emphysema presence. The model computed the two best fitting regression lines on the expiratory phase of the flow-volume loop and calculated the angle between them. The collapse was expressed as an Angle of collapse (AC) which was then correlated with the presence of emphysema. Findings were validated in an independent group of 340 individuals. RESULTS: AC in emphysema subjects (N = 251) was significantly lower (131° ± 14°) compared to AC in subjects without emphysema (N = 223), (152° ± 10°) (p < 0.0001). Multivariate regression analysis revealed AC as best indicator of visually scored emphysema (R2 = 0.505, p < 0.0001) with little significant contribution of KCO, %predicted and FEV1, %predicted to the total model (total R2 = 0.626, p < 0.0001). Similar associations were obtained when using CT-automated density scores for emphysema assessment. Receiver operating characteristic (ROC) curves pointed to 131° as the best cut-off for emphysema (95.5% positive predictive value, 97% specificity and 51% sensitivity). Validation in a second group confirmed the significant difference in mean AC between emphysema and non-emphysema subjects. When applying the 131° cut-off, a positive predictive value of 95.6%, a specificity of 96% and a sensitivity of 59% were demonstrated. CONCLUSIONS: Airway collapse on forced expiration quantified by a computer model correlates with emphysema. An AC below 131° can be considered as a specific cut-off for predicting the presence of emphysema in heavy smokers.