Adrenal Gland Necrosis in Pregnancy: How to Manage? Case Series at Nantes University Hospital and Literature Review.

Adrenal necrosis is a rare but serious cause of abdominal pain of thrombotic origin during pregnancy. There is often a delay in diagnosis and treatment. The objective was to specify the clinical and paraclinical signs suggestive of adrenal necrosis, making it possible to improve the delay in diagnostic. The secondary objective was to establish a multidisciplinary protocol regarding management. This is a case report of pregnant women with a radiological diagnosis of adrenal gland necrosis. In parallel, we carried out a systematic review in the same period. We studied these patients' clinical, biological and radiological data. We included eight patients with a computed tomography scan diagnosis of adrenal necrosis and fifteen articles in the literature describing twenty-four cases. All the patients presented with the same symptoms. The treatment was based on curative anticoagulation. The diagnosis of adrenal gland necrosis is worth suggesting in view of the array of sudden morphine-resistant abdominal pain associated with a biological inflammatory syndrome. The diagnosis is based on the computed tomography scan. Three to six months of curative anticoagulation is recommended as well as a thrombophilia and endocrinological assessment to rule out adrenal insufficiency.

Cemiplimab-induced cytokine-release syndrome: second case reported and review of the literature.

Cemiplimab, a human monoclonal antibody directed against PD-1, has provided more options in the treatment of locally advanced or metastatic cutaneous squamous-cell carcinoma at an unresectable state. Immune checkpoint inhibitors can induce several unfavorable reactions generally referred to as immune-related adverse effects. Cytokine-release syndrome is an immune-related adverse event that is infrequent and not well known. Diagnosis is difficult because of the unspecific symptoms (e.g., fever, hypotension) but it can also be life threatening. The authors report the case of a 62-year-old treated by cemiplimab for a cutaneous squamous-cell carcinoma of the diaper fold with iliac and inguinal lymph node extension. He presented with severe cytokine-release syndrome, concluding with the discontinuation of cemiplimab.

Immunotherapy has become an increasingly important part of cancer treatment. This treatment has many side effects, mainly linked with immune system activation. Cytokine-release syndrome is one of the rare complications; it causes hyperthermia, hypotension and biological inflammation. Diagnosis of this syndrome is critical, as it can be life threatening. Diagnosis and early management, including stopping immunotherapy and administering corticosteroids and, in some cases, anti-IL- 6, leads to a favorable outcome in the majority of cases. The authors report the second case of cytokine-release syndrome after cemiplimab infusion used in the first-line treatment of cutaneous unresectable squamous-cell carcinoma.

Antiphospholipid syndrome in patients over 65 years: A comparative study of clinical and biological features and thrombotic relapses.

OBJECTIVE: The aim of the study was to describe clinical and biological characteristics and thrombotic relapses of patients diagnosed with antiphospholipid syndrome (APS) after the age of 65 years, in comparison with patients diagnosed with APS before 65. METHODS: This retrospective multicenter study was performed to 2005 from 2017 and included patients diagnosed with APS after the age of 65 years, in accordance with Sydney criteria. We compared these patients with APS patients diagnosed before the age of 65 years, and with control thrombotic patients older than 65 years. RESULTS: Fifty-eight APS patients over the age of 65 years were compared to 127 APS patients aged less than 65 and to 58 controls. In elderly APS versus younger APS, there was a male predominance (58.6% vs 36.2% p = .001); myocardial infarction and lower limb deep vein thrombosis (LLDVT) were more frequent in elderly, respectively, 12.1% versus 1.6% (p = .005), and 44.8% versus 29.9% (p = .048). Anticardiolipin antibody (aCL) IgM was more frequently found in old patients compared to younger patients (33.9% vs 18.1%, p = .02), contrary to lupus anticoagulant (LAC) (52.8% vs 66.9%, p = .02). Older patients were more often diagnosed with single positive APS (82.8% vs 59.8% p = .002). The thrombotic relapse free survival was lower in elderly APS patients (p = .044) compared to younger APS. Elderly APS patients had more recurrent arterial and venous thrombosis (p = .03) and had poorer overall survival (p = .004) than elderly controls. CONCLUSION: In this study, APS was different in patients aged more than 65 years, with a male predominance and more myocardial infarctions and LLDVT at diagnosis. Single antiphopholipid positivity and aCL IgM were more frequent in older patients. Older patient with APS had more thrombotic recurrence during follow-up. Compared to elderly controls, elderly APS patients had more thrombosis recurrences and poorer survival.

Pharmaco-mechanical catheter-directed thrombolysis versus recanalization and stenting for post thrombotic syndrome after lower limb deep vein thrombosis: a comparative study.

Background: Endovenous interventional procedures can be used in addition to therapeutic anticoagulation to treat deep vein thrombosis in selected patients with proximal vein involvement (vena cava, iliac and/or common femoral). The aim of this study was to compare venous patency and the post-thrombotic syndrome (PTS) in patients treated with pharmaco-mechanical catheter-directed thrombolysis (PMT) versus recanalization-stenting for PTS after a proximal lower limb deep vein thrombosis. Methods: Between January 2014 and December 2020, this retrospective and monocentric study included patients with very symptomatic acute iliofemoral deep vein thrombosis treated with PMT within 21 days after diagnosis (PMT group) and patients with PTS caused by chronic venous obstruction treated with recanalization and stenting (CRS group). Results: A total of 116 patients were included (26 PMT, 90 CRS). The rate of primary patency was 81.8% (18/22 patients) in the PMT group and 78.4% (69/88) in the CRS group (P>0.99). The rate of venous patency at the last follow-up was 76.9% (20/26) in the PMT group and 82.2% (74/90) in the CRS group (P=0.57). The median number of stents was 2 (range, 0-5) in the PMT group and 3 (range, 0-7) in the CRS group (P<0.001). The median stent length was 150 mm (range, 60-390 mm) and 280 mm (range, 120-820 mm), respectively (P<0.001). The median last Villalta score was 2 (range, 0-10) in the PMT group and 2 (range, 0-21) in the CRS group (P=0.55). The rate of venous claudication at the last follow-up was 19.0% (4/21) in the PMT group and 12.0% (10/83) in the CRS group (P=0.47). Conclusions: In this study, there was no difference in venous patency and in the rate and severity of PTS between the PMT and CRS groups. The number of stent and their length were significantly lower in the PMT group compared with the CRS group.

Case-Control Study on Exercise-Induced Vasculitis in Hikers.

The aim of this study was to identify clinical factors associated with exercise-induced vasculitis (EIV). This study included EIV cases and controls matched for age. Cases included were all members of a hiking club and participated in extended hiking trips. Exercise-induced vasculitis was diagnosed based on clinical signs occurring only after prolonged walks. Chronic venous disease was defined using the Clinical Etiological Anatomical Pathophysiologic classification. This study included 162 hikers: 32 EIV cases and 130 matched controls. Mean age at EIV diagnosis was 47.1 years and 24 (75.0%) of EIV cases were women. Chronic venous disease was present in 19 (57.6%) of EIV cases vs 39 (30.0%) in controls (P = .001); those with EIV had significantly more saphenous vein insufficiency and C3 venous insufficiency than controls, 85.0 vs 52.6% and 8 (25.0%) vs 13 (10.0%) (P = .02), respectively. For EIV cases, mean walking distance per hike was significantly higher than for controls (P = .002). Exercise-induced vasculitis symptoms were typical with rash and/or purpura on the leg in warm conditions. Lesions spontaneously disappear in <10 days. In this study, EIV cases had more chronic venous disease and longer mean walking distances than controls.

Prevalence of post-thrombotic syndrome in a cohort of upper extremity vein thrombosis.

OBJECTIVE: Post-thrombotic syndrome (PTS) is one of the main complications that occurs after venous thrombosis. There are few data on the proportion of patients that will develop upper extremity PTS (UE-PTS) after upper extremity venous thrombosis (UEVT). The main objective of the study was to assess the prevalence of PTS in a UEVT cohort and to identify predictive factors of UE-PTS. METHODS: This study included patients with a history of proximal or arm UEVT, diagnosed on duplex ultrasound examination, between January 1, 2015, and December 31, 2017, in a university hospital. After UEVT, each patient was evaluated by a prospective standardized recording of clinical manifestations and duplex ultrasound examination in case of upper limb symptoms. UE-PTS was defined as a modified Villalta score of 4 or higher. RESULTS: Ninety-two patients were included; 68 (73.9%) had deep vein thrombosis (DVT) and 24 (19.2%) arm superficial vein thrombosis. Thirteen patients had PTS (14.1%), 12 (17.6%) in the DVT group and 1 (4.2%) in the superficial vein thrombosis group. There was a history of DVT in 92.3% of the cases of PTS. PTS was more frequent in patients with strokes with limb movement reduction (P = .01). On multivariate Cox analysis, a history of stroke (hazard ratio, 5.4; 95% confidence interval, 1.46-20.22; P = .01) was predictive of UE-PTS. CONCLUSIONS: UE-PTS occurred in 14.1% of cases after UEVT. Stroke with a decrease in limb movement was a predictor of developing PTS. Diagnostic criteria should be established for UE-PTS and prospective studies are needed to improve the description and management of UE-PTS.

Risk factors for symptomatic vascular events in giant cell arteritis: a study of 254 patients with large-vessel imaging at diagnosis.

AIMS: To identify factors associated with vascular events in patients with giant cell arteritis (GCA). METHODS: We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who all underwent vascular imaging evaluation at diagnosis. Symptomatic vascular events were defined as the occurrence of any aortic event (aortic dissection or symptomatic aortic aneurysm), stroke, myocardial infarction, limb or mesenteric ischemia and de novo lower limbs arteritis stage 3 or 4. Patients with symptomatic vascular event (VE+) and without were compared, and risk factors were identified in a multivariable analysis. RESULTS: Thirty-nine (15.4%) of the 254 included patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months. Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were more frequent in VE+ patients (p < 0.05), as an abnormal computed tomography (CT)-scan at diagnosis (p = 0.04), aortitis (p = 0.01), particularly of the descending thoracic aorta (p = 0.03) and atheroma (p = 0.03). Deaths were more frequent in the VE+ group (37.1 versus 10.3%, p = 0.0003). In multivariable analysis, aortic surgery [hazard ratio (HR): 10.46 (1.41-77.80), p = 0.02], stroke [HR: 22.32 (3.69-135.05), p < 0.001], upper limb ischemia [HR: 20.27 (2.05-200.12), p = 0.01], lower limb ischemia [HR: 76.57 (2.89-2027.69), p = 0.009], aortic atheroma [HR: 3.06 (1.06-8.82), p = 0.04] and aortitis of the descending thoracic aorta on CT-scan at diagnosis [HR: 4.64 (1.56-13.75), p = 0.006] were independent predictive factors of a vascular event. CONCLUSION: In this study on GCA cases with large vessels imaging at diagnosis, aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event. PLAIN LANGUAGE SUMMARY: Risk factors for symptomatic vascular events in giant cell arteritisThis study was performed to identify the risk factors for developing symptomatic vascular event during giant cell arteritis (GCA) because these are poorly known.We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who all underwent vascular imaging evaluation at diagnosis.Patients with symptomatic vascular event (VE+) and without (VE-) were compared, and risk factors were identified in a multivariable analysis.Thirty-nine patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months.Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were significantly more frequent in VE+ patients, as an abnormal CT-scan at diagnosis, aortitis, particularly of the descending thoracic aorta and atheroma. Deaths were more frequent in the VE+ group.Among 254 GCA patients, 39 experienced at least one vascular event during follow-up.Aortic surgery, stroke, upper and lower limb ischemia were vascular event risk factors.Aortic atheroma and descending thoracic aorta aortitis on CT-scan were vascular event risk factors.This study on GCA cases with large vessels imaging at diagnosis, showed that aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event.

Large-vessel involvement is predictive of multiple relapses in giant cell arteritis.

BACKGROUND: Giant cell arteritis (GCA) is the most common systemic vasculitis. Relapses are frequent. The aim of this study was to identify relapse risk factors in patients with GCA with complete large-vessel imaging at diagnosis. METHODS: Patients with GCA followed in our institution between April 1998 and April 2018 were included retrospectively. We included only patients who had undergone large vascular imaging investigations at diagnosis by computed tomography (CT)-scan and/or positron emission tomography (PET)-scan and/or angio-magnetic resonance imaging (MRI). Clinical, biological, and radiological data were collected. Relapse was defined as the reappearance of GCA symptoms, with concomitant increase in inflammatory markers, requiring treatment adjustment. Relapsing patients (R) and non-relapsing patients (NR) were compared. Relapse and multiple relapses (>2) risk factors were identified in multivariable Cox analyses. RESULTS: This study included 254 patients (73.2% women), with a median age of 72 years at diagnosis and a median follow up of 32.5 months. At diagnosis, 160 patients (63%) had an inflammatory large-vessel involvement on imaging, 46.1% (117 patients) relapsed at least once, and 21.3% (54 patients) had multiple relapses. The median delay of first relapse after diagnosis was 9 months. The second relapse delay was 21.5 months. NR patients had more stroke at diagnosis than R (p = 0.03) and the brachiocephalic trunk was involved more frequently on CT-scan (p = 0.046), as carotids (p = 0.02) in R patients. Multivariate Cox model identified male gender [hazard ratio (HR): 0.51, confidence interval (CI) (0.27-0.96), p = 0.04] as a relapse protective factor, and peripheral musculoskeletal manifestations [HR: 1.74 (1.03-2.94), p = 0.004] as a relapse risk factor. Peripheral musculoskeletal manifestations [HR: 2.78 (1.23-6.28), p = 0.014], negative temporal artery biopsy [HR: 2.29 (1.18-4.45), p = 0.015], large-vessel involvement like upper limb ischemia [HR: 8.84 (2.48-31.56), p = 0.001] and inflammation of arm arteries on CT-scan [HR: 2.39 (1.02-5.58), p = 0.04] at diagnosis were risk factors of multiple relapses. CONCLUSION: Male gender was a protective factor for GCA relapse and peripheral musculoskeletal manifestations appeared as a relapsing risk factor. Moreover, this study identified a particular clinical phenotype of multi-relapsing patients with GCA, characterized by peripheral musculoskeletal manifestations, negative temporal artery biopsy, and large-vessel involvement with upper limb ischemia or inflammation of arm arteries. PLAIN LANGUAGE SUMMARY: At giant cell arteritis diagnosis, large-vessel inflammatory involvement is predictive of multiple relapses 46.1% of patients with GCA relapse, and 21.3% undergo multiple relapses;Male gender appears as a protective factor for relapsing in GCA;Peripheral musculoskeletal manifestations are a relapse and multiple relapses risk factor;A negative temporal artery biopsy is predictive of multiple relapses;Large-vessel involvement is predictive of multiple relapses.

Predictive factors of venous recanalization in upper-extremity vein thrombosis.

BACKGROUND: Upper extremity venous thrombosis (UEVT) represents about 10% of venous thrombo-embolic disease. This is mainly explained by the increasing use of central venous line, for oncologic or nutritional care. The factors associated with venous recanalization are not known. OBJECTIVE: The aim of this study was to investigate prognosis factor associated with venous recanalization after UEVT. METHODS: This study included patients with UEVT diagnosed with duplex ultra-sonography (DUS) from January 2015 to December 2017 with DUS evaluations during follow-up. A multivariate Cox proportional-hazards-model analysis was performed to identify predictive factors of UEVT complete recanalization. RESULTS: This study included 494 UEVT, 304 proximal UEVT and 190 distal UEVT. The median age was 58 years, 39.5% were women. Clinical context was: hematological malignancy (40.7%), solid cancer (14.2%), infectious or inflammatory context (49.9%) and presence of venous catheters or pacemaker leads in 86.4%. The rate of recanalization without sequelae of UEVT was 38%. For all UEVT, in multivariate analysis, factors associated with complete vein recanalization were: thrombosis associated with central venous catheter (CVC) (HR:2.40, [1.45;3.95], p<0.001), UEVT limited to a venous segment (HR:1.94, [1.26;3.00], p = 0.003), occlusive thrombosis (HR:0.48 [0.34;0.67], p<0.0001), the presence of a PICC Line (HR:2.29, [1.48;3.52], p<0.001), a thrombosis of deep and distal topography (HR:1.70, [1.10;2.63], p = 0.02) or superficial thrombosis of the forearm (HR:2.79, [1.52;5.12], p<0.001). For deep and proximal UEVT, non-occlusive UEVT (HR:2.23, [1.49;3.33], p<0.0001), thrombosis associated with CVC (HR:1.58, [1.01;2.47], p = 0.04) and infectious or inflammatory context (HR:1.63, [1.10;2.41], p = 0.01) were factors associated with complete vein recanalization. CONCLUSION: In this study, factors associated with UEVT recanalization were UEVT limited to a venous segment, thrombosis associated with CVC, a thrombosis of deep and distal thrombosis topography and superficial thrombosis of the forearm. Occlusive thrombosis was associated with the absence of UEVT recanalization.

Digital ischaemia aetiologies and mid-term follow-up: A cohort study of 323 patients.

ABSTRACT: Upper extremity digital ischaemia (UEDI) is a rare heterogeneous condition whose frequency is 40 times less than that of toe ischaemia. Using a large cohort, the aim of this study was to evaluate aetiologies, prognosis and midterm clinical outcomes of UEDI.All patients with UEDI with or without cutaneous necrosis in a university hospital setting between January 2000 to December 2016 were included. Aetiologies, recurrence of UEDI, digital amputation and survival were analyzed retrospectively.Three hundred twenty three patients were included. UEDI due to cardio-embolic disease (DICE) was the highest occurring aetiology with 59 patients (18.3%), followed by DI due to Systemic Sclerosis (SSc) (16.1%), idiopathic causes (11.7%), Thromboangiitis obliterans (TAO) (9.3%), iatrogenic causes (9.3%), and cancer (6.2%). DICE patients tended to be older and featured more cases with arterial hypertension whereas TAO patients smoked more tobacco and cannabis. During follow-up, recurrences were significantly more frequent in SSc than in all other tested groups (P < .0001 vs idiopathic and DICE, P = .003 vs TAO) and among TAO patients when compared to DICE patients (P = .005). The cumulated rate of digital amputation was higher in the SSc group (n = 18) (P = .02) and the TAO group (n = 7) (P = .03) than in DICE (n = 2).This retrospective study suggests that main aetiologies of UEDI are DICE, SSc and idiopathic. This study highlights higher frequency of iatrogenic UEDI than previous studies. UEDI associated with SSc has a poor local prognosis (amputations and recurrences) and DICE a poor survival. UEDI with SSc and TAO are frequently recurrent.

Effect of cannabis consumption on characteristics and evolution of thromboangitis obliterans.

Background: Thromboangiitis obliterans (TAO) is a distal non atherosclerotic thrombotic vasculitis affecting tobacco smokers. The role of cannabis co-exposure remains controversial. The study aims to assess how cannabis consumption influences clinical presentation and outcome of TAO in tobacco smokers. Patients and methods: TAO patients, according to Papa's criteria, were included in a retrospective bicentric study between the 1st January 2003 and the 1st march 2020. Clinical characteristics, arterial involvement at TAO diagnosis, vascular event and amputations during follow-up were analyzed according to cannabis consumption. Results: Seventy-three patients with TAO patients were included. Forty-five patients were in Tobacco group (T) and 28 in Tobacco and cannabis group (T&C). Tobacco exposure was less important in T&C group than in T group (19.4±11.3 vs 31.6±16.6 pack-years) (p=0.005) and patients in T&C group were younger at TAO diagnosis than in T group (p=0.008). Patients in T&C group presented more claudication (33.3% vs 8.9%, p=0.01) and less upper limbs resting ischemia (25.9% vs 51.1%, p=0.04) than patients in the T group. No differences were found between groups with regard to arterial distribution. Amputation rate for patients who had at least one major or minor amputation did not differ between T and T&C group (25% vs 14.8%, p=0.38). Conclusions: Cannabis consumption was associated with a younger age of TAO onset. However, it does not affect amputation-free survival, Tobacco exposure is less important in T&C patients; data of this bicentric study suggest that cannabis could be a cofactor of tobacco which accelerates TAO onset.

Symptomatic aortitis at giant cell arteritis diagnosis: a prognostic factor of aortic event.

BACKGROUND: Giant cell arteritis (GCA) is frequently associated with aortic involvement that is likely to cause life-threatening structural complications (aneurysm, dissection). Few studies have investigated the occurrence of these complications, and no predictive factor has been identified so far. The aim of this study was to investigate factors associated with the risk of aortic complications in a cohort of GCA aortitis. METHODS: Data of all patients managed with aortitis (CT or 18 FDG PET) at the diagnosis of GCA in five hospitals from May 1998 and April 2019 were retrospectively collected. Clinical features were compared according to the presence of aortitis symptoms. The predictive factors of occurrence or aggravation of aortic structural abnormalities were investigated. RESULTS: One hundred and seventy-one patients with GCA aortitis were included; 55 patients (32%) had symptoms of aortitis (dorsal/lumbar/abdominal pain, aortic insufficiency) at diagnosis. The median follow-up was 38 months. Aortic complications occurred after a median time of 32 months. There were 19 new aortic aneurysms or complications of aneurysm and 5 dissections. Survival without aortic complication was significantly different between the symptomatic and non-symptomatic groups (Log rank, p = 0.0003). In multivariate analysis the presence of aortitis symptoms at diagnosis (HR 6.64 [1.95, 22.6] p = 0.002) and GCA relapse (HR 3.62 [1.2, 10.9] p = 0.02) were factors associated with the occurrence of aortic complications. CONCLUSION: In this study, the presence of aortitis symptoms at the diagnosis of GCA aortitis and GCA relapse were independent predictive factors of occurrence of aortic complications during follow-up.

Pulmonary Embolism and Deep Vein Thrombosis in COVID-19: A Systematic Review and Meta-Analysis.

Background The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the diagnostic accuracy of D-dimer tests for PE is unknown. Purpose To conduct meta-analysis of the study-level incidence of PE and DVT and to evaluate the diagnostic accuracy of D-dimer tests for PE from multicenter individual patient data. Materials and Methods A systematic literature search identified studies evaluating the incidence of PE or DVT in patients with COVID-19 from January 1, 2020, to June 15, 2020. These outcomes were pooled using a random-effects model and were further evaluated using metaregression analysis. The diagnostic accuracy of D-dimer tests for PE was estimated on the basis of individual patient data using the summary receiver operating characteristic curve. Results Twenty-seven studies with 3342 patients with COVID-19 were included in the analysis. The pooled incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9; I2 = 0.93) and 14.8% (95% CI: 8.5, 24.5; I2 = 0.94), respectively. PE was more frequently found in patients who were admitted to the intensive care unit (ICU) (24.7% [95% CI: 18.6, 32.1] vs 10.5% [95% CI: 5.1, 20.2] in those not admitted to the ICU) and in studies with universal screening using CT pulmonary angiography. DVT was present in 42.4% of patients with PE. D-dimer tests had an area under the receiver operating characteristic curve of 0.737 for PE, and D-dimer levels of 500 and 1000 µg/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%, respectively). Conclusion Pulmonary embolism (PE) and deep vein thrombosis (DVT) occurred in 16.5% and 14.8% of patients with coronavirus disease 2019 (COVID-19), respectively, and more than half of patients with PE lacked DVT. The cutoffs of D-dimer levels used to exclude PE in preexisting guidelines seem applicable to patients with COVID-19. © RSNA, 2020 Supplemental material is available for this article. See also the editorial by Woodard in this issue.

Systematic assessment of venous thromboembolism in COVID-19 patients receiving thromboprophylaxis: incidence and role of D-dimer as predictive factors.

Coagulopathy in COVID-19 is a burning issue and strategies to prevent thromboembolic events are debated and highly heterogeneous. The objective was to determine incidence and risk factors of venous thromboembolism (VTE) in COVID-19 inpatients receiving thromboprophylaxis. In this retrospective French cohort study, patients hospitalized in medical wards non-ICU with confirmed COVID-19 and adequate thromboprophylaxis were included. A systematic low limb venous duplex ultrasonography was performed at hospital discharge or earlier if deep venous thrombosis (DVT) was clinically suspected. Chest angio-CT scan was performed when pulmonary embolism (PE) was suspected. Of 71 patients, 16 developed VTE (22.5%) and 7 PE (10%) despite adequate thromboprophylaxis. D-dimers at baseline were significantly higher in patients with DVT (p < 0.001). Demographics, comorbidities, disease manifestations, severity score, and other biological parameters, including inflammatory markers, were similar in patients with and without VTE. The negative predictive value of a baseline D-dimer level < 1.0 µg/ml was 90% for VTE and 98% for PE. The positive predictive value for VTE was 44% and 67% for D-dimer level ≥ 1.0 µg/ml and ≥ 3 µg/ml, respectively. The association between D-dimer level and VTE risk increased by taking into account the latest available D-dimer level prior to venous duplex ultrasonography for the patients with monitoring of D-dimer. Despite thromboprophylaxis, the risk of VTE is high in COVID-19 non-ICU inpatients. Increased D-dimer concentrations of more than 1.0 µg/ml predict the risk of venous thromboembolism. D-dimer level-guided aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies.

Long-term efficacy and safety of 2CdA (cladribine) in extra-pulmonary adult-onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review.

Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete picture of the efficacy and safety of 2CdA (2-chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a-LCH) patients who received single-agent 2CdA and a systematic literature review. All had previously received systemic therapy (vinblastine, n = 19). Response to 2CdA was evaluable in 22 cases. Overall response rate (ORR) was 91%. Complete response (CR) occurred in 11 cases (50%). Nine patients (39%) developed grade 3-4 neutropenia and/or severe infection. A literature review yielded 48 additional cases. A pooled analysis confirmed our findings (ORR: 88%, CR: 49%). CRs were rare with cumulative dose <50 mg/m2 . Disease progression rates were 20% and 30% at two and five years, respectively. Partial response (PR) to 2CdA was predictive of disease progression. Among eight re-treated patients, five went into CR, two in PR, and one died. Single-agent 2CdA is effective in reactivated a-LCH, including at intermediate doses. Toxicity, significant but acceptable, warrants infectious prophylaxis. Complete responders may enter prolonged remission. Further studies are needed to determine 2CdA sequencing with other agents (vinblastine, cytarabine).

A STROBE cohort study of 755 deep and superficial upper-extremity vein thrombosis.

Upper extremity vein thrombosis (UE-VT) are more and more frequent pathologies and yet little studied. The aim is to describe the clinical and ultrasound features, UE-VT-related diseases, and the prevalence of pulmonary embolism (PE) and associated deaths.All UE-VT patients diagnosed by Doppler-ultrasound in Nantes University Hospital, from January 2015 to December 2017, were included retrospectively. UE-VT suspicion patterns, clinical features, UE-VT topography, and prevalence of PE and death were analyzed.Seven hundred and fifty-five UE-VT were analyzed, including 427 deep thrombosis (UE-DVT) and 328 superficial thrombosis (UE-SVT). In 86.2% (n = 651) UE-VT were related to endovascular devices. Among these thrombosis, one third is in connection with a PICC LINE and one quarter with a peripheral venous line. Forty nine percent (n = 370) of the patients had solid neoplasia or hematological malignancies. An inflammatory or systemic infectious context was found in 40.8% (n = 308) of the cases. The most frequently observed clinical sign at the UE-VT diagnosis was edema (28.6%). Among the UE-SVT it was the presence of an indurated cord (33.2%) and among the UE-DVT the indication of the Doppler-ultrasound was mainly a suspicion of infection on endovascular device (35.1%). In 10.6% (n = 80) of the cases the UE-VT were asymptomatic. The most frequently thrombosed veins were brachial basilic veins (16.7% of all thrombosed segments) followed by jugular (13%) and subclavian (12.3%) veins; 61.3% (n = 463) of UE-VT were in the right upper extremity; 63.3% (n = 478) UE-VT were occlusive. The occurrence of PE is 4% and the death rate is 10.2%, mainly related to the severe comorbidities of patients with UE-VT.UE-VT occurs in particular clinical contexts (hematological malignancies, solid cancers, systemic infections) and in the majority of endovascular devices (86.2%). The occurrence of PE is low.

Resistant Hypertension: Novel Insights.

Hypertension is the most common chronic disease and the leading risk factor for disability and premature deaths in the world, accounting for more than 9 million deaths annually. Resistant hypertension is a particularly severe form of hypertension. It was described 50 years ago and since then has been a very active field of research. This review aims at summarizing the most recent findings on resistant hypertension. The recent concepts of apparent- and true-resistant hypertension have stimulated a more precise definition of resistant hypertension taking into account not only the accuracy of blood pressure measurement and pharmacological class of prescribed drugs but also patient adherence to drugs and life-style recommendations. Recent epidemiological studies have reported a 10% prevalence of resistant hypertension among hypertensive subjects and demonstrated the high cardiovascular risk of these patients. In addition, these studies identified subgroups of patients with even higher morbidity and mortality risk, probably requiring a more aggressive medical management. In the meantime, guidelines provided more standardized clinical work-up to identify potentially reversible causes for resistant hypertension such as secondary hypertension. The debate is however still ongoing on which would be the optimal method(s) to screen for non-adherence to hypertension therapy, recognized as the major cause for (pseudo)-resistance to treatment. Recent randomized clinical trials have demonstrated the strong benefit of anti-aldosterone drugs (mostly spironolocatone) as fourth-line therapies in resistant hypertension whereas clinical trials with device-based therapies displayed contrasting results. New trials with improved devices and more carefully selected patients with resistant hypertension are ongoing.

Bilateral Pulmonary Embolism Following a Viper Envenomation in France: A Case Report and Review.

Complications following snake bites are not common in France. We report the case of a bilateral pulmonary embolism following a viper envenomation in France.A healthy 72-year-old female presented with a lower limb hematoma following a viper bite. She was admitted at the hospital 2 days later and received low-molecular-weight heparin because of bed rest. Seven days later, she complained of thoracic pain and respiratory failure, and a bilateral pulmonary was diagnosed, without biological sign of neither disseminated intravascular coagulation nor coagulation trouble. Repeated lower limbs Doppler ultrasound were normal.This case is particularly interesting because it is only the 7th reported case of pulmonary embolism following a snake envenomation; moreover, it happened in France where poisonous snakes are very rare.Several hypotheses have been made to explain this late localized coagulopathy: an increased level of unstable fibrin produced by thrombin-like glycoproteins from the venom is one of them.

Comparison of idiopathic (isolated) aortitis and giant cell arteritis-related aortitis. A French retrospective multicenter study of 117 patients.

OBJECTIVES: The aim of the study was to compare clinical/imaging findings and outcome in patients with idiopathic (isolated aortitis, IA) and with giant cell arteritis (GCA)-related aortitis. METHODS: Patients from 11 French internal medicine departments were retrospectively included. Aortitis was defined by aortic wall thickening >2mm and/or an aortic aneurysm on CT-scan, associated to inflammatory syndrome. Patients with GCA had at least 3 ACR criteria. Aortic events (aneurysm, dissection, aortic surgeries) were reported, and free of aortic events-survival were compared. RESULTS: Among 191 patients with non-infectious aortitis, 73 with GCA and 44 with IA were included. Patients with IA were younger (65 vs 70 years, p=0.003) and comprised more past/current smokers (43 vs 15%, p=0.0007). Aortic aneurisms were more frequent (38% vs 20%, p=0.03), and aortic wall thickening was more pronounced in IA. During follow-up (median=34 months), subsequent development of aortic aneurysm was significantly lower in GCA when compared to IA (p=0.009). GCA patients required significantly less aortic surgery during follow-up than IA patients (p=0.02). Mean age, sex ratio, inflammatory parameters, and free of aortic aneurism survival were equivalent in patients with IA ≥ 60 years when compared to patients with GCA-related aortitis. CONCLUSIONS: IA is more severe than aortitis related to GCA, with higher proportions of aortic aneurism at diagnosis and during follow-up. IA is a heterogeneous disease and its prognosis is worse in younger patients <60 years. Most patients with IA ≥ 60 years share many features with GCA-related aortitis.