Could it be VEXAS?

We report the case of the youngest patient described with VEXAS syndrome associated with MDS-IB1, successfully treated with azacitidine-venetoclax and allogeneic stem cell transplant.

Higher prevalence of splenic artery aneurysms in hereditary hemorrhagic telangiectasia: Vascular implications and risk factors.

BACKGROUND: Splenic artery aneurysm (SAA) is a rare but potentially fatal condition. Rupture results in 25% mortality up to 75% in pregnant women with 95% fetal mortality. Brief reports suggest an increased risk of developing SAA in patients with HHT. METHODS: We analyzed enhanced multidetector CT data in 186 HHT patients matched (gender and ± 5 year old) with 186 controls. We screened for SAA and recorded diameter of splenic and hepatic arteries and hepatic, pancreatic and splenic parenchymal involvements. We determined by univariate and multivariate analysis, the relationship with age, sex, genetic status, cardiovascular risk factors (CVRF) and visceral involvement. RESULTS: SAA concerned 24.7% of HHT patients and 5.4% of controls, p<0.001. Factors associated with increased risk of SAA in HHT were female gender (p = 0.04, OR = 2.12, IC 95% = 1.03-4.50), age (p = 0.0003, OR = 1.04, 95% CI = 1.02-1.06) and pancreatic parenchymal involvement (p = 0.04, OR = 2.13, 95% CI = 1.01-4.49), but not type of mutation, hepatic or splenic parenchymal involvements, splenic size or splenic artery diameter or CVRF. CONCLUSIONS: We found a 4.57 higher rate of SAA in HHT patients without evidence of splenic high output related disease or increased CVRF. These results suggest the presence of a vascular intrinsic involvement. It should lead to screening all HHT patients for SAA. The vasculopathy hypothesis could require a change in management as screening of all systemic arteries and even the aorta and to further research in the field.

Radiofrequency ablation for colorectal cancer liver metastases initially greater than 25 mm but downsized by neo-adjuvant chemotherapy is associated with increased rate of local tumor progression.

BACKGROUND: Radiofrequency ablation (RFA) is a valid treatment for liver metastases from colorectal cancer (CRLM) smaller than 25 mm and unsuitable for surgical resection. Tumor size is predictive for local tumor progression (LTP). The aim of this study was to evaluate whether RFA is indicated for lesions >25 mm at presentation but <25 mm after chemotherapy. METHOD: Patients who underwent RFA for CRLM after chemotherapy (January 2004-December 2012) were reviewed. Metastases were classified according to their size. Group 1: ≤25 mm before and after chemotherapy. Group 2A: >25 mm before but ≤25 mm after chemotherapy. Group 2B: >25 mm before and after chemotherapy. RESULTS: 133 CRLM were ablated in 83 patients (median follow-up 56 months). At 1-year, the LTP rate was higher in group 2A than in group 1 (32% vs. 16%, p ≤ 0.001). The highest rate of 1-year LTP was 64% in group 2B. Time to LTP (TLTP) was shorter in group 2A than in group 1 (HR: 2.89; 95% CI [1.04-8.01]; p = 0.004). Following multivariate analysis, the group type was the only predictive factor for TLTP (p < 0.001). CONCLUSIONS: RFA is not the optimal treatment for CRLM > 25 mm at presentation.

Reliability of contrast echocardiography to rule out pulmonary arteriovenous malformations and avoid CT irradiation in pediatric patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: The overall risk of cancer is higher in people exposed to computed tomography (CT) scans in childhood or adolescence compared to adults. Transthoracic contrast echocardiography (TTCE) has recently been used to screen for pulmonary arteriovenous malformations (PAVMs) in children with hereditary hemorrhagic telangiectasia (HHT), but the value of TTCE to rule out PAVMs and avoid chest CT radiation has yet to be discussed. METHODS: Between 2003 and 2013, 92 pediatric patients with ≥3 Curaçao criteria and/or genetic mutation underwent TTCE and chest CT on the same day. We used the classification proposed by Barzilai for TTCE quantification of shunting. We considered CT findings as negative when no PAVMs or only one microscopic PAVM was detected. RESULTS: Mean age was 11.2 ± 4.1 years. The shunt was grade 0 on TTCE in 27.3%, grade 1 in 17%, grade 2 in 29.6%, grade 3 in 23.9%, and grade 4 in 2.2%. We found PAVMs on chest CT in 52.2%. All the patients with a grade 0 or 1 had a negative CT. The sensitivity and specificity of TTCE for the detection of PAVMs were 100% and 95.1%, respectively. The negative predictive value (NPV) was 100% and the positive predictive value (PPV) was 96%. CONCLUSIONS: A low-grade classification (Barzilai 0 or 1) could presumably exclude the presence of PAVMs and allow CT irradiation to be avoided in children and adolescents. The screening algorithm using TTCE first would allow more than 40% of the pediatric patients screened for PAVMs to be spared the radiation dose of CT.

High plasma levels of the pro-inflammatory cytokine IL-22 and the anti-inflammatory cytokines IL-10 and IL-1ra in acute pancreatitis.

BACKGROUND/OBJECTIVES: Pancreatic acinar cells are major targets of IL-22. Our aim is to study early plasma levels of IL-22, of pro- and anti-inflammatory cytokines in acute pancreatitis, and their association with severity or necrosis infection. METHODS: Consecutive patients admitted to the Department of Hepato-Gastroenterology at Poitiers University of Medicine Hospital (France) with a diagnosis of AP were prospectively enrolled. Plasma concentrations of IL-22, IL-6, IL-8, IL-1 α, IL-1ß, TNF- α, IFN-γ, IL-17A, IL-10, IL-1ra and IL-4 were assessed by multiple immunoassay at the admission time. A thoracoabdominal contrast-enhanced CT scan was performed at day 2. RESULTS: Sixty-two patients were included; 13 patients (21%) had a severe acute pancreatitis, 5 patients (8%) developed necrosis infection and 29 patients (47%) had pleural effusion. Plasma levels of IL-22 were high in AP (135 ± 31 vs 4.2 ± 1.8 pg/ml for controls, p < 0.05), but did not correlate with the severity of the disease, whereas IL-6, IL-10 and IL-1ra where enhanced in patients with severe acute pancreatitis and with pleural effusion. Patients who further developed necrosis infection had higher levels of IL-1ra at admission (p = 0.0004). CONCLUSION: In acute pancreatitis, high plasma levels of IL-22 are observed, regardless the severity of the disease. In contrast, severe forms were associated with increased levels of IL-6, IL-10 and IL-1ra. The beneficial or deleterious role of IL-22 in AP remains to be further studied.

Roles of cyclooxygenase 2 and hepatic venous flow in patients with HHT or hepatopulmonary syndrome.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) and hepatopulmonary syndrome are disorders characterized by the development of multiple pulmonary arteriovenous malformations (PAVM). PRESENTATION OF THE HYPOTHESIS: COX2 may be at the origin of a cascade of pro inflammatory events to favour angiogenesis and PAVM development. TESTING THE HYPOTHESIS: HHT and hepatopulmonary syndrome mouse models may be used to show its effects on PAVM formation. Anti COX-2 therapy could also be tested in human individuals, particularly in patients presenting a hepatopulmonary syndrome or HHT with small PAVM. IMPLICATION OF THE HYPOTHESIS: PAVMs are one of the main causes of morbidity in patients presenting with HHT disease, owing to the risks of rupture as well as paradoxical embolism exposing to stroke and/or cerebral abscess. Percutaneous embolization has become the treatment of choice of PAVM. Anti COX2 may prevent from PAVM development and subsequent related complications and avoid either surgery and/or percutaneous embolization and thus subsequent related complication.