Successful long-term systemic sclerosis treatment by high-frequent low-dose B cell-depleting therapy.

OBJECTIVES: Systemic sclerosis (SSc) is a multiorgan disease with a 10-year mortality rate of up to 50 %. B cell-depleting therapy with rituximab (RTX) appears effective in SSc treatment, but data from randomized controlled trials (RCTs) are lacking, and the frequency and dosage of RTX in SSc have no consensus. We aimed to evaluate the long-term efficacy and safety of quarterly RTX administration in SSc. METHODS: This study retrospectively analyzed 40 patients with SSC treated with RTX twice within 14 days every 3 months from 2010 to 2020. The patients fulfilled the LeRoy and the American College of Rheumatology/European League Against Rheumatism Criteria for SSc. Modified Rodnan skin score (mRSS), lung function test results, and serum immunoglobulin (IgG, IgA, and IgM) concentrations were analyzed. RESULTS: A total of 40 patients with SSc received RTX over a median time of 3.9 years (range: 1-10 years). The median mRSS (baseline: 19, 24 months: 16, p < 0.001) demonstrated a significant improvement, and the predicted forced vital capacity was stable. No new or unexpected safety signals, especially regarding treatment-related infectious adverse events, were observed. Immunoglobulin concentrations were within normal range, and specific antibodies to pneumococcal polysaccharides were preserved despite long-term B cell-depleting therapy. None of the patients died during the observation period of up to 10 years. CONCLUSION: SSc was effectively and safely treated with low-dose RTX quarterly. RCTs are warranted to validate the advantage of continuous B cell depletion by quarterly low-dose RTX administration compared to other treatment intervals.

COPART Risk Score, Endothelial Dysfunction, and Arterial Hypertension are Independent Risk Factors for Mortality in Claudicants.

OBJECTIVE: The COPART risk score consists of six variables to assess the prognosis of PAOD patients. The flow mediated dilation (FMD) quantifies endothelial function. The aim of this study was to evaluate the mortality prediction of these two variables in a long-term observation of claudicants. METHODS: 184 consecutive claudicants were included in a prospective observational study over a median observation period of 7.9 (IQR 7.2-8.7) years. The endothelial function was assessed on the day of study inclusion using brachial FMD. RESULTS: Three groups were assigned according to the COPART risk score: low risk (LR), n = 72 (39%); medium risk (MR), n = 59 (32%); and high risk (HR), n = 53 (29%). Overall survival rates differed among COPART risk score groups (p < .001, 5 year survival: LR group 83% [95% CI 74-92%]; MR group 73% [95% CI 62-84%]; HR group 57% [95% CI 43-70%]). Survivors had a significantly better median FMD than non-survivors (4.1% [IQR 1.2-6.4] vs. 1.3% [IQR 0.0-4.2]; p < .001). Also the FMD differed significantly among the three COPART risk groups (LR 4.0% [IQR 1.2-6.3], MR 2.3% [IQR 0.0-6.3], HR 1.7% [IQR 0.0-3.6]; p = .033). Finally, independent predictors for disease specific survival were COPART risk score (p = .033; MR group [HR 1.6], 95% CI 0.7-3.6; HR group [HR 2.7], 95% CI 1.2-5.8), FMD (p = .004; FMD ≤2.5 vs. >2.5, HR 2.6, 95% CI 1.4-4.9), and arterial hypertension (p = .039; HR 3.5, 95% CI 1.1-11.3). CONCLUSIONS: COPART risk score, FMD, and arterial hypertension are independent long-term mortality predictors in this group of claudicants. The best mortality assessment is provided by including all three predictors.

COPART Risk Score Predicts Long-term Mortality in Peripheral Arterial Occlusive Disease.

OBJECTIVES: The COhorte de Patients ARTériopathes (COPART) Risk Score is a risk score assessing the 1 year outcome of patients who received inpatient treatment because of their peripheral arterial occlusive disease (PAOD). The COPART Risk Score consists of six variables each of which is allocated a different number of points (age, history of myocardial infarction, C-reactive protein, ankle-brachial index, estimated glomerular filtration rate, medication with antiplatelet agents, statins and renin-angiotensin system inhibitors). METHODS: 129 consecutive claudicants were included in a prospective trial with an average follow up of 8.8 (± 0.7) years. All patients were hospitalized for their first endovascular procedure to the pelvic and/or femoropopliteal arteries. The endpoints were all cause mortality and cardiovascular (CV) death. The COPART Risk Score was calculated for the three patient cohorts (low risk: 52 patients [40.3%]; medium risk: 41 patients [31.8%]; high risk: 36 patients [27.9%]). RESULTS: During the follow up period 23.1% (n = 12) of patients in the low risk group, 34.1% (n = 14) of patients in the medium risk group, and 63.9% (n = 23) of patients in the high risk group died. CV death occurred in 11.5% in the low, 22.0% in the medium, and 41.7% in the high risk groups. The three groups differed significantly with regard to all cause and CV mortality (p < .0001 and p = .001). CONCLUSIONS: The COPART Risk Score is a suitable instrument to predict long-term all cause and CV mortality in claudicants preceding their first peripheral intervention.

Acute wiiitis representing as thrombosis of the inferior vena cava and left pelvic veins.

Deep venous thrombosis as a result of venous wall injury provoked by trauma is a common finding. It often occurs in patients with sportive overstraining, caused by over fatigue of the body structures. In 2007, the entity of "acute wiiitis" was first described in a letter to the New England Journal of Medicine. Acute wiiitis sums up all affections, mainly skeletal and muscle affections, provoked by playing Nintendo Wii, a very common and loved video-game system. Deep venous thrombosis as a consequence of Nintendo Wii has not been described so far. We present a patient with a massive free floating thrombus of the left pelvic veins originating from the gluteal veins and reaching into the inferior vena cava after playing Nintendo Wii.

Lymphocyte-to-monocyte ratio: a novel marker for critical limb ischemia in PAOD patients.

BACKGROUND: The lymphocyte-to-monocyte ratio (LMR) is easily determined from the white blood cell count. Lymphocytes were previously investigated as a part of the neutrophil-to-lymphocyte ratio (NLR) in patients with atherosclerotic disease and an elevated NLR was negatively associated with cardiovascular endpoints. As monocytes play a leading role in the progression of atherosclerosis, especially in peripheral arterial occlusive disease (PAOD), we investigated LMR and its association with critical limb ischemia and other vascular endpoints in PAOD patients. METHODS AND FINDINGS: We evaluated 2121 PAOD patients treated at our institution from 2005 to 2010. LMR was calculated and the cohort was divided into tertiles according to the LMR. An optimal cut-off value for the continuous LMR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non-CLI. In our cohort occurrence of CLI decreased significantly with an increase in LMR. An LMR of 3.1 was identified as an optimal cut-off. Two groups were categorized, one with 1021 patients (LMR < 3.1) and a second one with 1100 patients (LMR ≥ 3.1). CLI was more frequent in LMR < 3.1 patients [426 (41.7%)] than in LMR ≥ 3.1 patients [254 (23.1%)] (p < 0.001), as was also the case with prior myocardial infarction [60 (9.5%) vs. 35 (3.2%), p = 0.003] and congestive heart failure [136 (13.3%) vs. 66 (6.0%), p < 0.001). As to inflammatory parameters, C-reactive protein [median 9.0 mg/l (4.0-30.0) vs. median 4.0 mg/l (2.0-8.0)] and fibrinogen (median 438 mg/dl (350-563) vs. 372 mg/dl (316-459.5)] also differed significantly in the two patient groups (both p < 0.001). A LMR < 3.1 was associated with an odds ratio (OR) of 2.0 (95% CI 1.8-2.2, p < 0.001) for CLI, even after adjustment for other vascular risk factors. CONCLUSIONS: A decreased LMR is significantly associated with a high risk for CLI and other vascular endpoints. The LMR is an easily determinable, broadly available and inexpensive marker that could be used to identify patients at high risk for vascular endpoints.

Prime time for drug eluting balloons in SFA interventions?

Peripheral arterial disease most commonly affects the femoropopliteal segment. Despite enormous improvements in device and treatment technology the long-term patency rate and clinical benefit of endovascular treatment in the respective vascular bed is not satisfying. Drug coated balloon technology as a treatment option in femoropopliteal disease has shown encouraging results in first-in-man trials, which have now been proven in large randomized controlled trials.

Unusual deep vein thrombosis sites: magnetic resonance venography in patients with negative compression ultrasound and symptomatic pulmonary embolism.

OBJECTIVES: To evaluate the clinical characteristics of patients with pulmonary embolism (PE), negative compression ultrasound (CUS) of the lower limbs and detection of unusual deep vein thrombosis (DVT) sites by means of magnetic resonance (MR) venography. METHODS: A retrospective data analysis of PE patients hospitalized at our institution from April 2009 to 2011. RESULTS: From April 2009 to 2011, a total of 762 PE patients were treated at our institution. In 169 of these patients CUS for DVT was negative. In these patients MR venography was performed for further evaluation. We found venous thrombosis at unusual sites in 12 of these patients. Due to free floating thrombus masses and fear of life-threatening PE progression we inserted an inferior vena cava filter in three of these 12 patients. The leading venous thromboembolism risk factor in our patients was immobilization (5 patients, 41.7%). CONCLUSIONS: We conclude that especially in patients with PE and negative CUS of the lower limbs a thrombosis of the pelvic veins should be considered in case of symptoms for venous thrombosis in this area. Further diagnostic work-up with MR venography should be scheduled in these patients especially in patients with risk factor immobilization as therapeutic consequences might occur.

The angiosome concept in clinical practice: implications for patient-specific recanalization procedures.

Below-the-knee (BTK) disease with the clinical presentation of critical limb ischemia is associated with a high rate of limb loss due to minor and major amputations. The main problem is to find a way to optimize blood flow to the critical limb area. BTK joint the down-stream diverges into 3 arms which supply different areas. Different concepts exist how optimal blood flow to the critical ischemic areas BTK can be achieved, either by treating as many vessels as can be reopened by an endovascular procedure, or by going for the two main BTK vessels, or in an outstanding situation also to treat the inflow of collaterals to achieve as much blood flow down the foot as possible. Derived from plastic surgery for the purpose of healing of flaps, the angiosome concept has been developed. An angiosome is an anatomic unit of tissue (consisting of skin, subcutaneous tissue, fascia, muscle and bone) fed by a source artery and drained by specific veins. From that point of view it can be presumed that revascularization of the source artery to the angiosome might result in better wound healing and limb salvage rates. The angiosome treatment concept of BTK disease refers to the concept in cardiology, where discrimination of reversible ischemia areas is made and respective vessels leading to these areas are treated in a distinctive way.

Do novel oral anticoagulants do better than standard therapy in the treatment of deep vein thrombosis?

The focus of DVT treatment is the prevention of recurrence and thrombus migration by treatment with anticoagulants. The aim is to improve outcomes by reducing clot burden and by preventing thrombus propagation, in order to prevent PE and the development of long-term complication. Actually, initial therapy is parenteral anticoagulation, mainly with low molecular weight heparin followed by a vitamin K antagonist (VKA) for triggered and idiopathic DVT. The long term treatment suggestion with a VKA is for sure the most challenging therapeutic scenario, showing all the disadvantages of VKA especially in the onset phase when therapeutic levels of VKA are difficult to achieve. The difference between VKAs and NOACs is the fact, that NOACs target a specific factor in the coagulation cascade. At time now two pathways have been chosen for treatment options, the direct inhibition of active sites of thrombin and factor Xa. Routine monitoring is not required and the drugs can be administered in fixed doses, which should increase patient adherence to long term treatment. At time now, four novel anticoagulants are called to be options for DVT treatment. Rivaroxaban, apixaban and edoxaban are direct FXa inhibitors, whereas dabigtran etexilate is a direct thrombin inhibitor.

Intra-arterial injection, a rare but serious complication of sclerotherapy.

Intra-arterial injections represent the most feared complication of sclerotherapy for varicose veins. We present a case of an inadvertent intra-arterial injection of polidocanol at the left medial calf in a 59-year-old woman with subsequent arterial occlusions of the posterior tibial artery and foot arteries. Despite several therapeutic interventions, lower-limb amputation could not be prevented. We conducted a PubMed search for articles reporting arterial complications related to sclerotherapy, in order to evaluate aetiology, clinical presentation, therapeutic management and outcome of sclerotherapy-associated intra-arterial injections during the past 50 years. Intra-arterial injection of a sclerosing solution was reported in 63 cases, mostly after injection near the ankle region or the distal medial calf. Clinical presentation was frequently characterized by immediate pain during injection and distal ischaemia with subsequent tissue loss. Despite several treatment approaches, amputation could not be prevented in 31 cases (52.5%). The pathophysiology of arterial complications related to intra-arterial injection and advisable therapeutic interventions are discussed. Inadvertent intra-arterial injection represents a limb-threatening complication of sclerotherapy. Target-oriented and prompt therapy seems inevitable in order to reduce the risk of permanent tissue loss and amputation.

Impaired endothelial-dependent and endothelium-independent vasodilatation in patients with thromboangiitis obliterans.

BACKGROUND: Endothelial dysfunction is the key process in the development of atherosclerosis. The aim of our study was to evaluate endothelial dysfunction measured by the noninvasive technique of Celermajer that plays a role in the pathogenesis of thrombangitis obliterans. METHODS: A total of 36 patients with thrombangitiis obliterans ([TAO]; mean age 44.9 ± 1.3 years) were compared with 30 healthy individuals (mean age 36.1 ± 1.8 years). High frequency ultrasound was used to measure changes in response to reactive hyperemia (leading to flow-mediated endothelium-dependent dilatation) and in response to 0.4 mg sublingual nitroglycerin ([NTG]; leading to NTG-induced, endothelium-independent dilatation). RESULTS: Patients with TAO showed a lower but statistically not significant flow-mediated dilatation and a statistically significant reduced NTG-induced vasodilatation than the control group. CONCLUSION: Our results suggest that both mechanisms play a role in patients with TAO, the endothelium-independent impaired vasodilatation even in a more significant way than the impaired endothelium-dependent vasodilatation.

A high CHA(2)DS(2)-VASc score is associated with a high risk for critical limb ischemia in peripheral arterial occlusive disease patients.

BACKGROUND: The CHA(2)DS(2)-VASc (congestive heart failure, hypertension, age ≥ 75 years (doubled), type 2 diabetes, previous stroke, transient ischemic attack, or thromboembolism (doubled), vascular disease, age 65-75 years, and sex category) score was published as a predictive scoring model for stroke in atrial fibrillation patients. As multiple vascular risk factors are included in this score we evaluated the occurrence of critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients according to their CHA(2)DS(2)-VASc score independent of a coexisting atrial fibrillation. METHODS: We evaluated 2237 PAOD patients treated at our institution from 2005 to 2010. CHA(2)DS(2)-VASc score was calculated and the occurrence of CLI was investigated. Furthermore all constituents of the score were investigated concerning association with CLI. RESULTS: Frequency of CLI was higher in patients with a high CHA(2)DS(2)-VASc score. Age ≥ 75 years was associated with an increased risk for CLI (OR 3.0), as was age 65-75 years (OR 1.8), type 2 diabetes (OR 2.8), and the factor previous stroke, transient ischemic attack, or thromboembolism (OR 1.4). The occurrence of arterial hypertension was protective for CLI (OR 0.6). Sex and congestive heart failure were not associated with an increased CLI risk. CONCLUSION: High CHA(2)DS(2)-VASc score is associated with a high CLI risk. As not all constituents are equally associated with CLI and some are even protective, a new score including only some of the factors should be evaluated for the prediction of CLI.

Asymptomatic deep vein thrombosis and superficial vein thrombosis in ambulatory cancer patients: impact on short-term survival.

BACKGROUND: Asymptomatic venous thrombotic events (VTEs) are possible findings in ambulatory cancer patients. Data regarding the incidence and clinical impact of asymptomatic VTEs are conflicting. We therefore conducted a study to evaluate the occurrence of asymptomatic VTEs of the lower limbs in ambulatory cancer patients to further evaluate the association of these asymptomatic VTEs on survival during a 9-month follow-up period. METHODS: In our prospective cohort, we included 150 consecutive ambulatory cancer patients who were free of any clinical symptoms for VTEs. Compression ultrasound to detect deep vein thrombosis (DVT) and superficial venous thrombosis (SVT) of the lower limbs was performed by a vascular specialist in all patients at baseline. In case of pathological findings the patients were treated with low molecular weight heparin (LMWH) because of current established guidelines. The occurrence of death was investigated during a 9-month follow-up period. RESULTS: A total of 27 (18%) patients with VTEs were detected, which included 13 patients (8.7%) with a SVT and 16 patients (10.7%) showing a DVT. Two patients had both, a SVT and a DVT as well. During the 9-month follow-up period the occurrence of a VTE at baseline was associated with a 2.4-fold increased risk for death (HR 2.4 (1.2-5.3); P=0.03). CONCLUSION: Asymptomatic VTEs of the lower limbs in ambulatory cancer patients are frequently occurring concomitant features and are associated with poor survival during a 9-month follow-up period despite anticoagulation with LMWH.

Dabigatran in patients with atrial fibrillation: perioperative and periinterventional management.

In any type of invasive surgery, the patient's individual risk of thromboembolism has to be weighed against the risk of bleeding. Based on various everyday situations in clinical routine, the purpose of the present expert recommendations is to provide appropriate perioperative and periinterventional management for patients with atrial fibrillation undergoing long-term treatment with the thrombin inhibitor dabigatran. As we currently have no routine laboratory test to measure therapeutic levels of the substance or the risk of bleeding, general measures such as a standardized documentation of the patient's history, a sufficient time interval between the last preoperative dose and the procedure, and careful control of local hemostasis should be given special attention.

Percutaneous transluminal angioplasty versus primary stenting in infrapopliteal arteries in critical limb ischemia.

BACKGROUND: In endovascular recanalisation of infrapopliteal arteries, studies have already pointed out the value of balloon angioplasty, but for stent implantation very few randomized controlled data exist so far. PATIENTS AND METHODS: We conducted a randomized controlled prospective trial in patients with critical limb ischemia (CLI) comparing the effect of percutaneous transluminal balloon angioplasty (PTA) versus primary stenting in infrapopliteal arteries, concerning 1-year clinical benefit and reobstruction rate. RESULTS: 54 patients were either randomized for primary stenting (balloon expandable stent) or PTA alone, 33 patients were assigned to the PTA group, 21 patients to the stent group. The whole follow up period of 12 months was completed by 46 patients. Improvement by at least one Rutherford classification was reached by a total of 33 (75.0 %) of patients at month 12, 22 (81.5 %) in the PTA group and 11 (64.7 %) in the stent group. A complete ulcer healing at month 12 showed 21 (63.6 %) of all patients, with a higher percentage in patients treated with PTA alone 16 (80.0 %) vs 5 (38.5 %). 50.0 % of all patients showed re-obstruction over the follow-up period, 39.4 % of the PTA and 66.7 % of the stent group. At month 3 primary patency rate was nearly equal in both groups (76.7 % PTA vs 75.0 % stent), but drifted apart with the duration of the follow-up period, with a primary patency at month 12 in the PTA group of 48,1 % vs 35,3 % in the stent group. As for secondary patency at month 12 the PTA group showed a patency rate of 70.4 %, vs 52.9 % in the stent group. CONCLUSIONS: Primary stenting with balloon expandable stents in the infrapopliteal arteries does not outway the benefit of PTA alone with the application of modern hydrophilic balloon catheters in patients with CLI.

Cystic medial necrosis Erdheim Gsell as a rare reason for spontaneous rupture of the ascending aorta.

Spontaneous rupture of the ascending aorta is a life-threatening condition requiring immediate intervention. The rupture usually leads to sudden death as a result of hemopericardium or hemothorax. The underlying histopathological condition in the cases described so far was mostly an atheromatous plaque. Some other rare underlying conditions were also described. We report a case of cystic medial necrosis Erdheim Gsell as a reason for fatal spontaneous rupture of the ascending aorta.