Frequency of malignancy is high in patients admitted for a first venous thromboembolism episode: an observational study.

Patients with a cancer at time of first venous thromboembolism (VTE) have not been thoroughly analyzed. Our study aimed to (1) determine the frequency of cancer diagnosed in patients hospitalized for a first VTE episode, (2) investigate the characteristics of VTE and cancer in such patients. All consecutive adults patients hospitalized over a 6-years period for a first VTE episode in a tertiary care hospital were considered. Patients with congenital or acquired thrombophilia were excluded. Demographic, medical history, and follow up data were retrieved from medical records. 216 patients (63.6 ± 19.7 years, 63.4 % females) hospitalized for a first VTE were analyzed. Among them, 64 patients (29.6 %) had cancer, either revealed (n = 26) or already known (n = 38) at VTE diagnosis. Cancer was in an advanced stage in 26 patients (40.6 %). Patients with cancer were older and displayed a higher frequency of vena cava thrombosis, as compared to patients without cancer. VTE was more recurrent and mortality was higher in patients with cancer. Cancer occurred after VTE diagnosis in only 2 (2/127, 1.6 %) cases during a protracted follow-up of 24.1 ± 22.5 months. Overall, VTE preceded cancer diagnosis in only 3 % (2/66) of cases. Frequency of cancer is high among patients hospitalized for a first VTE. In such setting, VTE often involved unusual sites such as vena cava. In most cases, cancer was either already known or diagnosed at time of VTE, with a poor prognosis.

Epstein-Barr virus LMP2A reduces hyperactivation induced by LMP1 to restore normal B cell phenotype in transgenic mice.

Epstein-Barr virus (EBV) latently infects most of the human population and is strongly associated with lymphoproliferative disorders. EBV encodes several latency proteins affecting B cell proliferation and survival, including latent membrane protein 2A (LMP2A) and the EBV oncoprotein LMP1. LMP1 and LMP2A signaling mimics CD40 and BCR signaling, respectively, and has been proposed to alter B cell functions including the ability of latently-infected B cells to access and transit the germinal center. In addition, several studies suggested a role for LMP2A modulation of LMP1 signaling in cell lines by alteration of TRAFs, signaling molecules used by LMP1. In this study, we investigated whether LMP1 and LMP2A co-expression in a transgenic mouse model alters B cell maturation and the response to antigen, and whether LMP2A modulates LMP1 function. Naïve LMP1/2A mice had similar lymphocyte populations and antibody production by flow cytometry and ELISA compared to controls. In the response to antigen, LMP2A expression in LMP1/2A animals rescued the impairment in germinal center generation promoted by LMP1. LMP1/2A animals produced high-affinity, class-switched antibody and plasma cells at levels similar to controls. In vitro, LMP1 upregulated activation markers and promoted B cell hyperproliferation, and co-expression of LMP2A restored a wild-type phenotype. By RT-PCR and immunoblot, LMP1 B cells demonstrated TRAF2 levels four-fold higher than non-transgenic controls, and co-expression of LMP2A restored TRAF2 levels to wild-type levels. No difference in TRAF3 levels was detected. While modulation of other TRAF family members remains to be assessed, normalization of the LMP1-induced B cell phenotype through LMP2A modulation of TRAF2 may be a pathway by which LMP2A controls B cell function. These findings identify an advance in the understanding of how Epstein-Barr virus can access the germinal center in vivo, a site critical for both the genesis of immunological memory and of virus-associated tumors.

Positron emission tomography and computed tomography angiography for the diagnosis of giant cell arteritis: A real-life prospective study.

The use of 18F-fluoro-deoxyglucose positron emission tomography scan (FDG-PET) and computed tomography angiography (CTA) to improve accuracy of diagnosis of giant cell arteritis (GCA) is a very important clinical need. We aimed to compare the diagnostic performance of FDG-PET and CTA in patients with GCA.FDG-PET and CTA were acquired in all consecutive patients suspected for GCA. Results of FDG-PET and CTA were compared with the final diagnosis based on clinical judgment, temporal artery biopsy (TAB) findings, and ACR criteria. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for each method.Twenty-four patients suspected for GCA were included. Fifteen (62.5%) were ultimately diagnosed as having GCA. Among them, all fulfilled ACR criteria and 6 had biopsy-proven GCA. Strong FDG uptake in large vessels was found in 10 patients who all had GCA. Mean maximal standard uptake values (SUVmax) per patient measured at all the arterial territories were of 3.7 (range: 2.8-4.7). FDG uptake was negative in 14 patients including 9 and 5 patients without and with GCA, respectively. Mural thickening suggestive of aortitis or branch vessel arteritis was observed on CTA in 11 patients with and 2 patients without GCA. No mural thickening was observed in 11 patients including 7 patients without and 4 patients with GCA. Overall, sensitivity was 66.7% and 73.3%, specificity was 100% and 84.6%, NPV was 64.3% and 64.6%, and PPV was 100% and 84.6% of FDG-PET and CTA, respectively.Both FDG-PET and CTA have a strong diagnostic yield for the diagnosis of GCA. FDG-PET appeared to have a higher PPV as compared to CTA and may be the preferred noninvasive technique to explore patients with suspected GCA.

Life-Threatening Hypercalcemia Revealing Diffuse and Isolated Acute Sarcoid-Like Myositis: A New Entity? (A Case-Series).

Up to 50% patients with sarcoidosis display extra-pulmonary disease. However, initial and isolated (ie, without lung disease) acute muscular involvement associated with pseudo-malignant hypercalcemia is very uncommon. We report on 3 cases of life-threatening hypercalcemia revealing florid and isolated acute sarcoid-like myositis.All patients complained of fatigue, progressive general muscle weakness, and weight loss. Laboratory tests showed a severe life-threatening hypercalcemia (>3.4 mmol/L). Hypercalcemia was associated with increased serum level of 1,25-(OH)2 vitamin D and complicated with acute renal failure. One patient displayed acute pancreatitis due to hypercalcemia.In all cases, PET-scan, performed for malignancy screening, incidentally revealed an intense, diffuse, and isolated muscular fluorodeoxyglucose (FDG) uptake consistent with diffuse non-necrotizing giant cells granulomatous myositis demonstrated by muscle biopsy. Of note, creatine phosphokinase blood level was normal in all cases. No patients displayed the usual thoracic features of sarcoidosis.All patients were treated with high dose steroids and achieved rapid, complete, and sustained remission. A review of English and French publications in Medline revealed 5 similar published cases.Steroid-sensitive acute sarcoid-like myositis causing high calcitriol levels and life-threatening hypercalcemia should be recognized as a separate entity.

Positron emission tomography combined with computed tomography as a screening tool for occult malignancy in patients with unprovoked venous thromboembolism: an observational study.

Venous thromboembolism (VTE) can be the first clinical manifestation of an occult malignancy. We aimed to assess the value, in daily practice, of positron emission tomography combined with computed tomography (PET-CT) for occult malignancy diagnosis in patients with unprovoked VTE.All PET-CTs performed over 5-years period (from January 2009 to October 2013) in adult patients followed in the Department of Internal Medicine (Bichat Hospital, Paris, France) were retrospectively reviewed. Clinical history, imaging findings, and additional diagnostic tests performed because of PET-CT findings were analyzed.From January 2009 to October 2013, PET-CT was performed for malignancy diagnosis in 67 consecutive patients with unprovoked VTE. Seventeen patients were excluded because of congenital or acquired thrombophilia, known cancer, estrogen use, inability to confirm VTE diagnosis, or missing data. Fifty patients (25 women; mean age, 65.2 ± 15.9 years) were included. VTE was a first episode in 84% of cases. In 22 (44%) patients, PET-CT showed increased uptake suspicious for malignancy. After additional procedures, malignancy was confirmed in 12/22 patients. In all cases of confirmed malignancies, conventional computed tomography scan (CT-scan) had similar diagnosis yield, as compared with PET-CT. In 10/22 cases, the suspected diagnosis of malignancy could not be confirmed despite extensive workup including specialist visits (n = 5), magnetic resonance imaging (n = 4), gastrointestinal tract endoscopy (n = 3), endometrial biopsies (n = 2), and hysterectomy (n = 1). The cost of additional diagnosis procedures performed because of false positive PET-CT amounted to є1956/patient. Interestingly, considering CT-scan findings only, no further investigation would have been scheduled. No patient with negative or false positive PET-CT was diagnosed with cancer during a mean follow-up of 22 ± 13.6 months.A diagnosis strategy based on PET-CT screening for malignancy in patients with unprovoked VTE had limited diagnosis value and may lead to unnecessary alarming and money- and time-consuming investigations.