Lower respiratory tract amyloidosis: Presentation, survival and prognostic factors. A multicenter consecutive case series.

Lower-respiratory-tract (LRT) amyloidosis has rarely been investigated. Our study presents characteristics, outcomes and survival of LRT amyloidosis. This multicenter retrospective study, from 1995 to 2017, included 73 patients with amyloidosis and LRT involvement. Respiratory patterns were: tracheobronchial (n = 17), nodular (n = 10), interstitial (n = 14) or composite (several respiratory involvements, n = 32). Interstitial and composite patterns were associated with multi-organ amyloidosis (n = 37, 80%) while tracheobronchial and nodular patterns were associated with organ-limited amyloidosis (n = 21, 78%). Amyloid light chain (AL) amyloidosis was diagnosed in 43 patients (59%), mainly of lambda type (n = 33, 77%). Smokers' proportion was higher in tracheobronchial (71%) and nodular (90%) patterns than in interstitial (14%) and composite (34%) patterns. The B-cell neoplasms involved 15 patients (21%), solid neoplasms 8 (11%), connective tissue diseases 8 (11%) and multiple myeloma 6 (8%). The B-cell and solid neoplasms were most prevalent in nodular pattern. Median follow-up was 4.4 years (2.2-8.9). Twenty-four patients died, mostly from respiratory infection. Survival at 1, 5, 10 years was respectively 88%, 70% and 54% for multi-organ amyloidosis, 96%, 89% and 69% for organ-limited amyloidosis (P = .125). Tracheobronchial and nodular patterns survival was better than in other respiratory patterns (P = .039). Death risk factors (multivariate analysis) were: cardiac localization (hazard-ratio [HR] 4.3 [95% confidence interval 1.6-11.5]; P = .004), age (HR 2.1 [1.2-3.7]; P = .008) and dyspnea at diagnosis (HR 4.0 [1.3-12.3]; P = .014). Various LRT amyloidosis patterns depend on smoking habits, organ-limited or multi-organ extension and comorbidities. They are associated with a different survival, which is also predicted by age, cardiac localization and dyspnea at presentation.

Psychosocial risk factors for increased emergency hospital utilization by sickle cell disease patients: a systematic review protocol.

OBJECTIVE: To assess psychosocial risk factors for increased emergency hospital utilization by sickle cell patients. INTRODUCTION: Emergency hospital utilization by sickle cell disease patients is high but heterogeneous between patients and in a given patient over time. Psychosocial factors affect emergency hospital utilization and are a possible target to improve the management of sickle cell disease. INCLUSION CRITERIA: This review will include all original quantitative studies evaluating the impact of psychosocial risk factors on emergency hospital utilization by sickle cell disease patients. There will be no language restriction. METHODS: PubMed, Embase, CINAHL, PubPsych, LiSSa, and Web of Science will be searched using a peer-reviewed search strategy. Study selection and extraction of data will be performed independently by two authors. Discrepancies will be solved by consensus or, if needed, by a third author. The authors will assess study quality, as well as perform a narrative synthesis of included studies, and where possible, meta-analyses with evaluation of heterogeneity and publication bias. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019140435.

Prognostic Value of Hyponatremia During Acute Painful Episodes in Sickle Cell Disease.

BACKGROUND: Low plasma sodium concentration has been recognized as a prognostic factor in several disorders but never evaluated in sickle cell disease. The present study evaluates its value at admission to predict a complication in adult patients with sickle cell disease hospitalized for an initially uncomplicated acute painful episode. METHODS: The primary outcome of this retrospective study, performed between 2010 and 2015 in a French referral center for sickle cell disease, was a composite criterion including acute chest syndrome, intensive care unit transfer, red blood cell transfusion or inpatient death. Analyses were adjusted for age, sex, hemoglobin genotype and concentration, lactate dehydrogenase (LDH) concentration, and white blood cell count. RESULTS: We included 1218 stays (406 patients). No inpatient death occurred during the study period. Hyponatremia (plasma sodium ≤135 mmol/L) at admission in the center was associated with the primary outcome (adjusted odds ratio [OR] 1.95, 95% confidence interval [CI] 1.3-2.91, P = 0.001), with acute chest syndrome (OR 1.95 [95% CI 1.2-3.17, P = 0.008]), and red blood cell transfusion (OR 2.71 [95% CI 1.58-4.65, P <0.001]) but not significantly with intensive care unit transfer (OR 1.83 [95% CI 0.94-3.79, P = 0.074]). Adjusted mean length of stay was longer by 1.1 days (95% CI 0.5-1.6, P <0.001) in patients with hyponatremia at admission. CONCLUSIONS: Hyponatremia at admission in the medical department for an acute painful episode is a strong and independent prognostic factor of unfavorable outcome and, notably, acute chest syndrome. It could help targeting patients who may benefit from closer monitoring.

Role of endothelial AADC in cardiac synthesis of serotonin and nitrates accumulation.

Serotonin (5-HT) regulates different cardiac functions by acting directly on cardiomyocytes, fibroblasts and endothelial cells. Today, it is widely accepted that activated platelets represent a major source of 5-HT. In contrast, a supposed production of 5-HT in the heart is still controversial. To address this issue, we investigated the expression and localization of 5-HT synthesizing enzyme tryptophan hydroxylase (TPH) and L-aromatic amino acid decarboxylase (AADC) in the heart. We also evaluated their involvement in cardiac production of 5-HT. TPH1 was weakly expressed in mouse and rat heart and appeared restricted to mast cells. Degranulation of mast cells by compound 48/80 did not modify 5-HT cardiac content in mice. Western blots and immunolabelling experiments showed an abundant expression of AADC in the mouse and rat heart and its co-localization with endothelial cells. Incubation of cardiac homogenate with the AADC substrate (5-hydroxy-L-tryptophan) 5-HTP or intraperitoneal injection of 5-HTP in mice significantly increased cardiac 5-HT. These effects were prevented by the AADC inhibitor benserazide. Finally, 5-HTP administration in mice increased phosphorylation of aortic nitric oxide synthase 3 at Ser (1177) as well as accumulation of nitrates in cardiac tissue. This suggests that the increase in 5-HT production by AADC leads to activation of endothelial and cardiac nitric oxide pathway. These data show that endothelial AADC plays an important role in cardiac synthesis of 5-HT and possibly in 5-HT-dependent regulation of nitric oxide generation.