Adrenal involvement in the antiphospholipid syndrome: clinical and immunologic characteristics of 86 patients

To describe the clinical and immunologic characteristics of patients with adrenal involvement and antiphospholipid syndrome (APS), we conducted a computer-assisted (PubMed) search of the literature to identify all cases of primary adrenal insufficiency associated with antiphospholipid antibodies published in English, French, and Spanish from 1983 (when APS was first defined) through March 2002. We reviewed 86 patients (80 from the literature plus 6 from our cohort); 55% were male, and the mean age at presentation was 43 +/- 16 years. Sixty-one (71%) patients had primary APS, and 14 (16%) had systemic lupus erythematosus. In 31 (36%) patients, adrenal insufficiency was the first clinical manifestation of APS. Abdominal pain was present in 55% of patients, followed by hypotension (54%), fever (40%), nausea or vomiting (31%), weakness or fatigue (31%), and lethargy or altered mental status (19%). The main finding in imaging techniques was compatible with adrenal hemorrhage (59%) and in histopathologic study was a hemorrhagic infarction with vessel thrombosis (55%). Lupus anticoagulant was detected in 97% of patients and the anticardiolipin antibodies titer was positive in 93% of patients. Most patients (95%) were positive for the IgG isotype of anticardiolipin antibodies, whereas 40% were positive for the IgM isotype. Baseline cortisol levels were decreased in 98% of patients, ACTH hormone levels were increased in 96% of patients, and the cosyntropin stimulation test was positive in 100% of patients tested. Steroid replacement therapy was the most frequent treatment (84%), followed by anticoagulation (52%) and aspirin (6%). Thirty-two of 35 (91%) patients with prolonged anticoagulant therapy were in good health with a mean follow-up of 25 months, whereas 25 of the 69 (36%) patients with outcome data available had died. The results of the present review stress the clinical importance of systematic screening for lupus anticoagulant and anticardiolipin antibodies in all cases of adrenal hemorrhage or infarction. An initial screening for hypoadrenalism is mandatory in any antiphospholipid antibody-positive patient who complains of abdominal pain and undue weakness or asthenia.     

Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data

Purpose

The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury.

Methods

We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume.

Results

Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P?=?0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P?=?0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P?=?0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher V_T.

Conclusions

Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241).

     

Cardioversion by external electric shock for atrial fibrillation: does patient age affect immediate results?

The restoration of sinus rhythm by external electric shock in patients with persistent atrial fibrillation is a well established treatment. However, in current practice this treatment is generally indicated less in the elderly subject although this attitude is not factual. The objective of this work was to evaluate the immediate results of cardioversion by external electric shock, comparing the success rates in four age groups: under 60 years, between 60 and 69 years, between 70 and 79 years, and over 80 years. This study was performed on 182 consecutive patients aged from 25 to 89 years: 35 patients aged less than 60 years, 52 patients aged from 60 to 69 years, 65 patients aged from 70 to 79 years, and 30 patients aged 80 years or over. The success rates were 91.4% before 60 years, 90.4% between 60 and 69 years, 90.8% between 70 and 79 years, and 83.3% after 80 years. There was no significant difference between the success rates in the four age groups (p = 0.68). Among the other factors analysed, only the duration of atrial fibrillation and the body mass index significantly influenced the results of external electric shock in this series. This work suggests that age does not significantly influence the immediate results of external electric shock. According to these data it does not appear justified to contra-indicate cardioversion by external electric shock on the sole criterion of age.     

Circulating monoclonal immunoglobulins in Sjögren syndrome: prevalence and clinical significance in 237 patients

We conducted the current study to analyze the prevalence and clinical significance of circulating monoclonal immunoglobulins in patients with Sj?gren syndrome (SS), focusing on the association with extraglandular features, immunologic markers, hematologic neoplasia, and hepatitis C virus (HCV) infection. We performed serum immunoelectrophoresis in 200 patients with primary SS and 37 patients with HCV-related SS. All patients fulfilled 4 or more of the 1993 European classification criteria for SS.Of the 200 patients with primary SS, 35 (18%) presented circulating monoclonal immunoglobulins. The monoclonal bands identified were 20 IgG (13 kappa, 7 lambda), 10 IgM (5 kappa, 5 lambda), 2 IgAkappa, and 3 free circulating light chains. Of the 37 SS-HCV patients, 16 (43%) had circulating monoclonal immunoglobulins. The monoclonal bands identified were 10 IgMkappa, 5 IgGlambda, and 1 free light lambda chain. Compared with primary SS patients, SS-HCV patients presented a higher frequency of monoclonal immunoglobulins (43% vs 18%, p = 0.001), with monoclonal IgMkappa being the most frequent monoclonal band. Six (12%) of the 51 SS patients with circulating monoclonal immunoglobulins presented hematologic neoplasia, compared with 3 (1.6%) of those without monoclonal immunoglobulins (p = 0.004; odds ratio = 8.13; 95% confidence intervals, 1.64-51.54). In 2 of the 6 patients with monoclonal immunoglobulins and lymphoproliferative disorders, a change of the monoclonal component was detected in previous immunoelectrophoresis determinations before the development of hematologic neoplasia. Circulating monoclonal immunoglobulins were detected in nearly 20% of patients with primary SS, with monoclonal IgG being the most frequent type of immunoglobulin detected. In SS-HCV patients, the prevalence of monoclonal immunoglobulins was higher (43%), with monoclonal IgM being the most frequent type found. SS-HCV patients presented a more restrictive monoclonal expression (limited to either monoclonal IgMkappa or monoclonal IgGlambda) than primary SS patients, who showed all types of heavy and light chains.     

Discrepancy between simultaneous digital skin microvascular and brachial artery macrovascular post-occlusive hyperemia in systemic sclerosis

OBJECTIVE: Vascular impairment, a main feature of the pathogenesis of systemic sclerosis (SSc), involves both the macro- and the microvasculature. We compared and correlated simultaneously measured skin microvascular and brachial artery macrovascular post-occlusive hyperemia in 3 groups: patients with SSc, patients with primary Raynaud's phenomenon (RP), and healthy volunteers. METHODS: Thirty-three healthy volunteers, 36 patients with primary RP, and 42 patients with SSc were enrolled. For each subject, brachial artery flow-mediated dilation (FMD) and cutaneous post-occlusive reactive hyperemia (PORH) were simultaneously recorded after 5-minute occlusion of the brachial artery. Local thermal hyperemia, nitroglycerin-mediated dilation (NMD), intima-media thickness (IMT), and pulse wave velocity (PWV) were also assessed. RESULTS: Digital cutaneous peak PORH was altered in patients with primary RP and SSc compared to healthy controls, whereas FMD was not significantly different among all groups. We observed a correlation between digital peak cutaneous vascular conductance and brachial FMD in healthy controls (r = 0.49; p = 0.004), but not in patients with primary RP or SSc. Thermal hyperemia was altered only in patients with SSc. Brachial NMD, IMT, and PWV were not different among all groups. CONCLUSION: We observed a loss of the correlation between brachial FMD and digital cutaneous PORH in patients with SSc and primary RP. Microvascular function is impaired in SSc, whereas brachial artery endothelial function is normal.     

Long term outcome of patients with active Crohn's disease exhibiting extensive and deep ulcerations at colonoscopy

OBJECTIVE: Prediction of the clinical course of Crohn's disease (CD) is difficult in the long term. Our aim was to determine whether the presence of severe endoscopic lesions (SELs) may predict a higher risk of colectomy and penetrating complications. METHODS: All patients at our institution with active ileocoIonic CD who had colonoscopies between 1990 and 1996 were included in the study. SELs were defined as extensive and deep ulcerations covering more than 10% of the mucosal area of at least one segment of the colon. RESULTS: Among the 102 patients included, 53 had SELs at index colonoscopy. During the follow-up (median = 52 months), 37 patients underwent colonic resection. Probabilities of colectomy at 1, 3, and 8 yr were 20%, 26%, and 42%. Risk of colectomy was independently affected by the presence of SELs at index colonoscopy (relative risk [RR] = 5.43, 95% CI = 2.64-11.18), a Crohn's Disease Activity Index level greater than 288 (RR = 2.21, 95% CI = 1.09-4.47), and the absence of immunosuppressive therapy during the follow-up (RR = 2.44, 95% CI = 1.20-5.00). Probabilities of colectomy were, respectively, 31% and 6% at 1 yr, 42% and 8% at 3 yr, and 62% and 18% at 8 yr in patients with and without SELs. We performed a second analysis excluding the 14 patients operated on within the 3 months after the index colonoscopy: presence of SELs remained the only significant factor predictive of colectomy (RR = 6.72, 95% CI = 2.26-20.03). All six patients with penetrating complications during the follow-up had SELs at index colonoscopy. CONCLUSIONS: Patients with CD exhibiting deep and extensive ulcerations at colonoscopy have a more aggressive clinical course with an increased rate of penetrating complications and surgery.