ABSTRACT
The diagnosis of pulmonary embolism (PE) is nowadays based on the sequential use of several diagnostic tests rather than on a single test. These diagnostic strategies are safe and have been prospectively validated. The first step after identifying patients with suspicion of PE is to establish the pre-test clinical probability. Several scores are available in order to make a standardised and reproducible assessment of the clinical probability, and therefore represent precious diagnostic tools. Indeed, clinical probability guides further investigations. Indeed, in patients with a low or an intermediate clinical probability or an "unlikely" probability, PE can be safely ruled out by negative D-dimers in approximately one third of outpatients without additional imaging. In case of positive D-dimers and a high clinical probability or a "likely" clinical probability, CT pulmonary angiography is now the recommended imaging technique. However, lower limb venous compression ultrasound and ventilation/perfusion scans remain useful in patients with contra-indications to CT, mainly those with renal insufficiency. Finally, some novel diagnostic tests seem promising. For example, V/Q SPECT has arisen as a highly accurate test and a potential alternative to CTPA. However, prospective management outcome studies are still lacking and are warranted before its implementation in routine clinical practice.
Subject(s)
Pulmonary Embolism/diagnosis , Computed Tomography Angiography/methods , Diagnosis, Differential , Diagnostic Tests, Routine , Fibrin Fibrinogen Degradation Products/analysis , Humans , Pulmonary Embolism/blood , Pulmonary Embolism/pathology , Radiography, Thoracic/methods , Single Photon Emission Computed Tomography Computed TomographyABSTRACT
Essentials The evidence on how to manage life-threatening pregnancy-related pulmonary embolism (PE) is scarce. We systematically reviewed all available cases of (sub)massive PE until December 2016. Thrombolysis in such severe PE was associated with a high maternal survival (94%). The major bleeding risk was much greater in the postpartum (58%) than antepartum period (18%). SUMMARY: Background Massive pulmonary embolism (PE) during pregnancy or the postpartum period is a rare but dramatic event. Our aim was to systematically review the evidence to guide its management. Methods We searched Pubmed, Embase, conference proceedings and the RIETE registry for published cases of severe (submassive/massive) PE treated with thrombolysis, percutaneous or surgical thrombectomy and/or extracorporeal membrane oxygenation (ECMO), occurring during pregnancy or within 6 weeks of delivery. Main outcomes were maternal survival and major bleeding, premature delivery, and fetal survival and bleeding. Results We found 127 cases of severe PE (at least 83% massive; 23% with cardiac arrest) treated with at least one modality. Among 83 women with thrombolysis, survival was 94% (95% CI, 86-98). The risk of major bleeding was 17.5% during pregnancy and 58.3% in the postpartum period, mainly because of severe postpartum hemorrhages. Fetal deaths possibly related to PE or its treatment occurred in 12.0% of cases treated during pregnancy. Among 36 women with surgical thrombectomy, maternal survival and risk of major bleeding were 86.1% (95% CI, 71-95) and 20.0%, with fetal deaths possibly related to surgery in 20.0%. About half of severe postpartum PEs occurred within 24 h of delivery. Conclusions Published cases of thrombolysis for massive PE during pregnancy and the postpartum period suggest a high maternal and fetal survival (94% and 88%). In the postpartum period, given the high risk of major bleeding with thrombolysis, other therapeutic options (catheter [or surgical] thrombectomy, ECMO) may be considered if available.
Subject(s)
Embolectomy , Extracorporeal Membrane Oxygenation , Postpartum Period , Pregnancy Complications, Cardiovascular/therapy , Pulmonary Embolism/therapy , Thrombectomy , Thrombolytic Therapy , Adult , Embolectomy/adverse effects , Embolectomy/mortality , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/mortality , Female , Fetal Death , Humans , Postpartum Hemorrhage/mortality , Pregnancy , Pregnancy Complications, Cardiovascular/diagnosis , Pregnancy Complications, Cardiovascular/mortality , Pregnancy Complications, Cardiovascular/physiopathology , Pulmonary Embolism/diagnosis , Pulmonary Embolism/mortality , Pulmonary Embolism/physiopathology , Risk Factors , Severity of Illness Index , Thrombectomy/adverse effects , Thrombectomy/mortality , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Time Factors , Treatment Outcome , Young AdultABSTRACT
Advances in the management of patients with suspected pulmonary embolism (PE) have improved diagnostic accuracy and made management algorithms safer, easier to use, and well standardized. These diagnostic algorithms are mainly based on the assessment of clinical pretest probability, D-dimer measurement, and imaging tests-predominantly computed tomography pulmonary angiography. These diagnostic algorithms allow safe and cost-effective diagnosis for most patients with suspected PE. In this review, we summarize signs and symptoms of PE, current existing evidence for PE diagnosis, and focus on the challenge of diagnosing PE in special patient populations, such as pregnant women, or patients with a prior VTE. We also discuss novel imaging tests for PE diagnosis and highlight some of the additional challenges that might require adjustments to current diagnostic strategies, such as the reduced clinical suspicion threshold, resulting in a lower proportion of PE among suspected patients as well as the overdiagnosis of subsegmental PE.
Subject(s)
Hematology/methods , Pulmonary Embolism/diagnosis , Acute Disease , Algorithms , Computed Tomography Angiography , Cost-Benefit Analysis , Dyspnea/physiopathology , Female , Fibrin Fibrinogen Degradation Products/analysis , Hemorrhage , Humans , Lung/physiopathology , Magnetic Resonance Angiography , Male , Pregnancy , Probability , Pulmonary Alveoli/physiopathology , Radionuclide Imaging , Reproducibility of Results , Tomography, X-Ray ComputedABSTRACT
Essentials The simplified Geneva score allows easier pretest probability assessment of pulmonary embolism (PE). We prospectively validated this score in the ADJUST-PE management outcome study. The study shows that it is safe to manage patients with suspected PE according to this score. The simplified Geneva score is now ready for use in routine clinical practice. SUMMARY: Background Pretest probability assessment by a clinical prediction rule (CPR) is an important step in the management of patients with suspected pulmonary embolism (PE). A limitation to the use of CPRs is that their constitutive variables and corresponding number of points are difficult to memorize. A simplified version of the Geneva score (i.e. attributing one point to each variable) has been proposed but never been prospectively validated. Aims Prospective validation of the simplified Geneva score (SGS) and comparison with the previous version of the Geneva score (GS). Methods In the ADJUST-PE study, which had the primary aim of validating the age-adjusted D-dimer cut-off, the SGS was prospectively used to determine the pretest probability in a subsample of 1621 study patients. Results Overall, PE was confirmed in 294 (18.1%) patients. Using the SGS, 608 (37.5%), 980 (60.5%) and 33 (2%) were classified as having a low, intermediate and high clinical probability. Corresponding prevalences of PE were 9.7%, 22.4% and 45.5%; 490 (30.1%) patients with low or intermediate probability had a D-dimer level below 500 µg L-1 and 653 (41.1%) had a negative D-dimer test according to the age-adjusted cut-off. Using the GS, the figures were 491(30.9%) and 650 (40.9%). None of the patients considered as not having PE based on a low or intermediate SGS and negative D-dimer had a recurrent thromboembolic event during the 3-month follow-up. Conclusions The use of SGS has similar efficiency and safety to the GS in excluding PE in association with the D-dimer test.
Subject(s)
Decision Support Techniques , Fibrin Fibrinogen Degradation Products/analysis , Pulmonary Embolism/diagnosis , Aged , Biomarkers/blood , Clinical Decision-Making , Europe/epidemiology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prevalence , Prognosis , Prospective Studies , Pulmonary Embolism/blood , Pulmonary Embolism/epidemiology , Pulmonary Embolism/therapy , Reproducibility of Results , Retrospective Studies , Risk FactorsABSTRACT
Essentials Safety of computed tomography (CTPA) to exclude pulmonary embolism (PE) in all patients is debated. We analysed the outcome of PE-likely outpatients left untreated after negative CTPA alone. The 3-month venous thromboembolic risk in these patients was very low (0.6%; 95% CI 0.2-2.3). Multidetector CTPA alone safely excludes PE in patients with likely clinical probability. SUMMARY: Background In patients with suspected pulmonary embolism (PE) classified as having a likely or high pretest clinical probability, the need to perform additional testing after a negative multidetector computed tomography pulmonary angiography (CTPA) finding remains a matter of debate. Objectives To assess the safety of excluding PE by CTPA without additional imaging in patients with a likely pretest probability of PE. Patients/Methods We retrospectively analyzed patients included in two multicenter management outcome studies that assessed diagnostic algorithms for PE diagnosis. Results Two thousand five hundred and twenty-two outpatients with suspected PE were available for analysis. Of these 2522 patients, 845 had a likely clinical probability as assessed by use of the simplified revised Geneva score. Of all of these patients, 314 had the diagnosis of PE excluded by a negative CTPA finding alone without additional testing, and were left without anticoagulant treatment and followed up for 3 months. Two patients presented with a venous thromboembolism (VTE) during follow-up. Therefore, the 3-month VTE risk in likely-probability patients after a negative CTPA finding alone was 2/314 (0.6%; 95% confidence interval [CI] 0.2-2.3%). Conclusions In outpatients with suspected PE and a likely clinical probability as assessed by use of the simplified revised Geneva score, CTPA alone seems to be able to safely exclude PE, with a low 3-month VTE rate, which is similar to the VTE rate following the gold standard, i.e. pulmonary angiography.
Subject(s)
Computed Tomography Angiography/methods , Multidetector Computed Tomography/methods , Pulmonary Artery/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Venous Thromboembolism/diagnostic imaging , Aged , Ambulatory Care , Computed Tomography Angiography/adverse effects , Europe , Female , Humans , Male , Middle Aged , Multidetector Computed Tomography/adverse effects , Patient Safety , Predictive Value of Tests , Prognosis , Radiation Dosage , Radiation Exposure/adverse effects , Reproducibility of Results , Retrospective Studies , Risk Assessment , Risk Factors , Time FactorsABSTRACT
OBJECTIVE: To characterize the risk of postpartum venous thromboembolism (VTE) associated with body-mass-index (BMI) in both pre-pregnancy and at delivery, and with gestational weight gain (GWG). METHODS: In a population-based, case-control study, we identified all women in Washington State with ICD-9 codes for VTE in the postpartum period between 2003 and 2011. Controls were women without VTE in the postpartum period, matched by delivery year to cases. Pre-pregnancy BMI, delivery BMI, and covariates were abstracted from birth certificates. Adjusted logistic regression models separately estimated postpartum VTE risk associated with categories of BMI in pre-pregnancy and at delivery. RESULTS: Cases (n=289) had a higher mean BMI than controls (n=4208) pre-pregnancy (29.9kg/m(2) and 26.3kg/m(2), respectively) and at delivery (34.8kg/m(2) vs. 31.4kg/m(2), respectively), with similar gestational weight gains. Compared with women with a normal pre-pregnancy BMI (18.5-24.9kg/m(2)), overweight (BMI 25-29.9kg/m(2)) and obese (BMI≥30kg/m(2)) women were at a 1.5-fold and 1.8-4 fold greater risk of postpartum VTE, respectively, with greatest risks in women with class III obesity (BMI≥40kg/m(2): OR 4.0, 95%CI 2.7-6.3). Observed associations of delivery BMI with postpartum VTE were less strong than those of pre-pregnancy BMI. Large weight gains during pregnancy (>22kg) also contributed to greater VTE risks (OR 1.5, 95%CI 1.0-2.2). CONCLUSION: Maternal BMI is an important risk factor for postpartum VTE, grading from weak in overweight women to very strong in women with class III obesity. Care providers may prefer to use pre-pregnancy BMI, along gestational weight gain, when stratifying the risk of postpartum VTE at delivery.
Subject(s)
Venous Thrombosis/etiology , Body Mass Index , Case-Control Studies , Female , Humans , Postpartum Period , Pregnancy , Pregnancy Complications, Cardiovascular , Risk Factors , Weight GainABSTRACT
BACKGROUND: Venous ultrasonography is the cornerstone of the diagnostic work-up in patients with suspected deep vein thrombosis (DVT). Significant variations exist in clinical practice between centers and/or countries, e.g. proximal vs. whole-leg ultrasound, serial tests vs. single test, and combination with clinical probability and D-dimer testing. Fewer data exist on the need for bilateral leg imaging. OBJECTIVES: To assess the yield of bilateral leg ultrasonography in patients with suspected DVT. PATIENTS AND METHODS: This was a retrospective cohort study of consecutive patients with clinically suspected DVT. A single whole-leg ultrasound scan was performed in all patients. We extracted information on demographics, risk factors, clinical signs, pretest probability, side of clinical suspicion, and ultrasound results. RESULTS AND CONCLUSIONS: Among the 2804 included patients, 609 (21.8%) patients had a positive ultrasound finding. A total of 20 patients (0.8%; 95% confidence interval [CI] 0.5-1.2%) had a thrombus diagnosed in both the symptomatic leg and asymptomatic leg. Moreover, five patients (0.2%; 95% CI 0.1-0.5%) did not have a thrombus in the symptomatic leg but had a thrombus in the asymptomatic leg. Two of 2540 patients with unilateral symptoms had no proximal DVT in the symptomatic leg and a proximal DVT in the asymptomatic leg (0.08%; 95% CI 0.0-0.3%). In summary, systematic imaging of both legs in patients with suspected DVT has a very low yield, and therefore does not appear to be justified.
Subject(s)
Lower Extremity/blood supply , Ultrasonography, Doppler , Veins/diagnostic imaging , Venous Thrombosis/diagnostic imaging , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Switzerland , Unnecessary ProceduresABSTRACT
Clinical probability and D-dimer measurement play an essential role in the non-invasive diagnostic strategies for pulmonary embolism (PE). PE can be ruled out without further imaging in patients with non-high clinical probability and negative D-dimer. D-dimer level is increased in patients with renal impairment. Whether its diagnostic usefulness is maintained in these patients is not well determined. We aimed to evaluate the effects of renal impairment on diagnostic performances of D-dimer in patients with suspected PE. A retrospective analysis of 1,625 patients with suspected PE included in a multicentre prospective study was performed. D-dimer levels and percentages of patients with a negative D-dimer were compared between three subgroups according to glomerular filtration rate (GFR) estimated by the MDRD formula: ≥90 ml/min (normal renal function), 60-89 ml/min (mild renal impairment), 30-59 ml/min (moderate renal impairment). D-dimer levels increased and the proportion of negative D-dimer decreased significantly according to renal status: 46% negative D-dimer in patients with normal GFR, 31% in patients with mild renal impairment, 11% in those with moderate renal impairment, corresponding to number of patients needed to test to obtain one negative test of 2.2, 3.2 and 9, respectively. In conclusion, the clinical usefulness of D-dimer decreases with renal impairment. However, PE can still be ruled out by negative D-dimer in a substantial proportion of patients with non-high clinical probability, avoiding exposure to contrast media.
Subject(s)
Fibrin Fibrinogen Degradation Products/metabolism , Kidney/metabolism , Pulmonary Embolism/diagnosis , Renal Insufficiency/diagnosis , Adult , Aged , Aged, 80 and over , Creatinine/metabolism , Female , Glomerular Filtration Rate , Humans , Kidney/pathology , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Pulmonary Embolism/complications , Renal Insufficiency/complications , Retrospective StudiesABSTRACT
Chronic critical ischemia of the lower limb (CCLI) is the most severe form of peripheral arterial disease. This terminology reflects the need to compare treatments based on an accurate and objective description of the clinical cases rather than subjective items like limb threatening ischemia or intervention for limb salvage. At the stage of CCLI the prognosis is very poor with a high risk of major amputation or disability or death. This highlights the importance of a precise clinical evaluation (including an hemodynamic reading of the clinical assessment of the foot) and of the use of the appropriate diagnostic tools to confirms CCLI diagnosis. This approach is invaluable for the correct stratification of the amputation risk.
Subject(s)
Ischemia/diagnosis , Leg/blood supply , Chronic Disease , Critical Illness , HumansABSTRACT
Non-invasive vascular studies can provide crucial information on the presence, location, and severity of critical limb ischaemia (CLI), as well as the initial assessment or treatment planning. Ankle-brachial index with Doppler ultrasound, despite limitations in diabetic and end-stage renal failure patients, is the first-line evaluation of CLI. In this group of patients, toe-brachial index measurement may better establish the diagnosis. Other non-invasive measurements, such as segmental limb pressure, continuous-wave Doppler analysis and pulse volume recording, are of limited accuracy. Transcutaneous oxygen pressure (TcPO(2)) measurement may be of value when rest pain and ulcerations of the foot are present. Duplex ultrasound is the most important non-invasive tool in CLI patients combining haemodynamic evaluation with imaging modality. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the next imaging studies in the algorithm for CLI. Both CTA and MRA have been proven effective in aiding the decision-making of clinicians and accurate planning of intervention. The data acquired with CTA and MRA can be manipulated in a multiplanar and 3D fashion and can offer exquisite detail. CTA results are generally equivalent to MRA, and both compare favourably with contrast angiography. The individual use of different imaging modalities depends on local availability, experience, and costs. Contrast angiography represents the gold standard, provides detailed information about arterial anatomy, and is recommended when revascularisation is needed.
Subject(s)
Arterial Occlusive Diseases/diagnosis , Diabetic Foot/diagnosis , Diagnostic Imaging , Ischemia/diagnosis , Lower Extremity/blood supply , Peripheral Vascular Diseases/diagnosis , Algorithms , Critical Illness , Decision Making , Hemodynamics , Humans , Risk Assessment , Sensitivity and SpecificityABSTRACT
Critical limb ischaemia (CLI) is a particularly severe manifestation of lower limb atherosclerosis posing a major threat to both limb and life of affected patients. Besides arterial revascularisation, risk-factor modification and administration of antiplatelet therapy is a major goal in the treatment of CLI patients. Key elements of cardiovascular risk management are smoking cessation and treatment of hyperlipidaemia with dietary modification or statins. Moreover, arterial hypertension and diabetes mellitus should be adequately treated. In CLI patients not suitable for arterial revascularisation or subsequent to unsuccessful revascularisation, parenteral prostanoids may be considered. CLI patients undergoing surgical revascularisation should be treated with beta blockers. At present, neither gene nor stem-cell therapy can be recommended outside clinical trials. Of note, walking exercise is contraindicated in CLI patients due to the risk of worsening pre-existing or causing new ischaemic wounds. CLI patients are oftentimes medically frail and exhibit significant comorbidities. Co-existing coronary heart and carotid as well as renal artery disease should be managed according to current guidelines. Considering the above-mentioned treatment goals, interdisciplinary treatment approaches for CLI patients are warranted. Aim of the present manuscript is to discuss currently existing evidence for both the management of cardiovascular risk factors and treatment of co-existing disease and to deduct specific treatment recommendations.
Subject(s)
Arterial Occlusive Diseases/prevention & control , Diabetic Foot/prevention & control , Ischemia/prevention & control , Lower Extremity/blood supply , Peripheral Vascular Diseases/prevention & control , Adrenergic beta-Antagonists/therapeutic use , Contraindications , Critical Illness , Diabetes Mellitus/prevention & control , Diet , Exercise Therapy , Genetic Therapy , Humans , Hyperlipidemias/prevention & control , Hypertension/prevention & control , Platelet Aggregation Inhibitors/therapeutic use , Prostaglandins/therapeutic use , Risk Assessment , Risk Factors , Smoking Cessation , Stem Cell Transplantation , Vascular Surgical ProceduresABSTRACT
The concept of chronic critical limb ischaemia (CLI) emerged late in the history of peripheral arterial occlusive disease (PAOD). The historical background and changing definitions of CLI over the last decades are important to know in order to understand why epidemiologic data are so difficult to compare between articles and over time. The prevalence of CLI is probably very high and largely underestimated, and significant differences exist between population studies and clinical series. The extremely high costs associated with management of these patients make CLI a real public health issue for the future. In the era of emerging vascular surgery in the 1950s, the initial classification of PAOD by Fontaine, with stages III and IV corresponding to CLI, was based only on clinical symptoms. Later, with increasing access to non-invasive haemodynamic measurements (ankle pressure, toe pressure), the need to prove a causal relationship between PAOD and clinical findings suggestive of CLI became a real concern, and the Rutherford classification published in 1986 included objective haemodynamic criteria. The first consensus document on CLI was published in 1991 and included clinical criteria associated with ankle and toe pressure and transcutaneous oxygen pressure (TcPO(2)) cut-off levels <50 mmHg, <30 mmHg and <10 mmHg respectively). This rigorous definition reflects an arterial insufficiency that is so severe as to cause microcirculatory changes and compromise tissue integrity, with a high rate of major amputation and mortality. The TASC I consensus document published in 2000 used less severe pressure cut-offs (≤ 50-70 mmHg, ≤ 30-50 mmHg and ≤ 30-50 mmHg respectively). The thresholds for toe pressure and especially TcPO(2) (which will be also included in TASC II consensus document) are however just below the lower limit of normality. It is therefore easy to infer that patients qualifying as CLI based on TASC criteria can suffer from far less severe disease than those qualifying as CLI in the initial 1991 consensus document. Furthermore, inclusion criteria of many recent interventional studies have even shifted further from the efforts of definition standardisation with objective criteria, by including patients as CLI based merely on Fontaine classification (stage III and IV) without haemodynamic criteria. The differences in the natural history of patients with CLI, including prognosis of the limb and the patient, are thus difficult to compare between studies in this context. Overall, CLI as defined by clinical and haemodynamic criteria remains a severe condition with poor prognosis, high medical costs and a major impact in terms of public health and patients' loss of functional capacity. The major progresses in best medical therapy of arterial disease and revascularisation procedures will certainly improve the outcome of CLI patients. In the future, an effort to apply a standardised definition with clinical and objective haemodynamic criteria will be needed to better demonstrate and compare the advances in management of these patients.
Subject(s)
Arterial Occlusive Diseases/diagnosis , Arterial Occlusive Diseases/epidemiology , Diabetic Foot/diagnosis , Diabetic Foot/epidemiology , Ischemia/diagnosis , Ischemia/epidemiology , Lower Extremity/blood supply , Peripheral Vascular Diseases/diagnosis , Peripheral Vascular Diseases/epidemiology , Critical Illness , Hemodynamics , Humans , Incidence , Prevalence , Prognosis , Risk Assessment , Risk FactorsABSTRACT
Recommendations stated in the TASC II guidelines for the treatment of peripheral arterial disease (PAD) regard a heterogeneous group of patients ranging from claudicants to critical limb ischaemia (CLI) patients. However, specific considerations apply to CLI patients. An important problem regarding the majority of currently available literature that reports on revascularisation strategies for PAD is that it does not focus on CLI patients specifically and studies them as a minor part of the complete cohort. Besides the lack of data on CLI patients, studies use a variety of endpoints, and even similar endpoints are often differentially defined. These considerations result in the fact that most recommendations in this guideline are not of the highest recommendation grade. In the present chapter the treatment of CLI is not based on the TASC II classification of atherosclerotic lesions, since definitions of atherosclerotic lesions are changing along the fast development of endovascular techniques, and inter-individual differences in interpretation of the TASC classification are problematic. Therefore we propose a classification merely based on vascular area of the atherosclerotic disease and the lesion length, which is less complex and eases the interpretation. Lesions and their treatment are discussed from the aorta downwards to the infrapopliteal region. For a subset of lesions, surgical revascularisation is still the gold standard, such as in extensive aorto-iliac lesions, lesions of the common femoral artery and long lesions of the superficial femoral artery (>15 cm), especially when an applicable venous conduit is present, because of higher patency and limb salvage rates, even though the risk of complications is sometimes higher than for endovascular strategies. It is however more and more accepted that an endovascular first strategy is adapted in most iliac, superficial femoral, and in some infrapopliteal lesions. The newer endovascular techniques, i.e. drug-eluting stents and balloons, show promising results especially in infrapopliteal lesions. However, most of these results should still be confirmed in large RCTs focusing on CLI patients. At some point when there is no possibility of an endovascular nor a surgical procedure, some alternative non-reconstructive options have been proposed such as lumbar sympathectomy and spinal cord stimulation. But their effectiveness is limited especially when assessing the results on objective criteria. The additional value of cell-based therapies has still to be proven from large RCTs and should therefore still be confined to a research setting. Altogether this chapter summarises the best available evidence for the treatment of CLI, which is, from multiple perspectives, completely different from claudication. The latter also stresses the importance of well-designed RCTs focusing on CLI patients reporting standardised endpoints, both clinical as well as procedural.
Subject(s)
Arterial Occlusive Diseases/therapy , Diabetic Foot/therapy , Ischemia/therapy , Limb Salvage/methods , Lower Extremity/blood supply , Peripheral Vascular Diseases/therapy , Angioplasty/methods , Arterial Occlusive Diseases/classification , Critical Illness , Cryotherapy , Humans , Ischemia/classification , Laser Therapy , Peripheral Vascular Diseases/classification , Practice Guidelines as Topic , Stents , Vascular Surgical Procedures/methodsABSTRACT
Ulcerated diabetic foot is a complex problem. Ischaemia, neuropathy and infection are the three pathological components that lead to diabetic foot complications, and they frequently occur together as an aetiologic triad. Neuropathy and ischaemia are the initiating factors, most often together as neuroischaemia, whereas infection is mostly a consequence. The role of peripheral arterial disease in diabetic foot has long been underestimated as typical ischaemic symptoms are less frequent in diabetics with ischaemia than in non-diabetics. Furthermore, the healing of a neuroischaemic ulcer is hampered by microvascular dysfunction. Therefore, the threshold for revascularising neuroischaemic ulcers should be lower than that for purely ischaemic ulcers. Previous guidelines have largely ignored these specific demands related to ulcerated neuroischaemic diabetic feet. Any diabetic foot ulcer should always be considered to have vascular impairment unless otherwise proven. Early referral, non-invasive vascular testing, imaging and intervention are crucial to improve diabetic foot ulcer healing and to prevent amputation. Timing is essential, as the window of opportunity to heal the ulcer and save the leg is easily missed. This chapter underlines the paucity of data on the best way to diagnose and treat these diabetic patients. Most of the studies dealing with neuroischaemic diabetic feet are not comparable in terms of patient populations, interventions or outcome. Therefore, there is an urgent need for a paradigm shift in diabetic foot care; that is, a new approach and classification of diabetics with vascular impairment in regard to clinical practice and research. A multidisciplinary approach needs to implemented systematically with a vascular surgeon as an integrated member. New strategies must be developed and implemented for diabetic foot patients with vascular impairment, to improve healing, to speed up healing rate and to avoid amputation, irrespective of the intervention technology chosen. Focused studies on the value of predictive tests, new treatment modalities as well as selective and targeted strategies are needed. As specific data on ulcerated neuroischaemic diabetic feet are scarce, recommendations are often of low grade.
Subject(s)
Diabetic Foot/diagnosis , Diabetic Foot/therapy , Amputation, Surgical , Debridement , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/therapy , Diagnostic Imaging , Humans , Ischemia/diagnosis , Ischemia/therapy , Peripheral Vascular Diseases/diagnosis , Peripheral Vascular Diseases/therapy , Practice Guidelines as Topic , Surgical Flaps , Vascular Surgical ProceduresABSTRACT
Structured follow-up after revascularisation for chronic critical limb ischaemia (CLI) aims at sustained treatment success and continued best patient care. Thereby, efforts need to address three fundamental domains: (A) best medical therapy, both to protect the arterial reconstruction locally and to reduce atherosclerotic burden systemically; (B) surveillance of the arterial reconstruction; and (C) timely initiation of repeat interventions. As most CLI patients are elderly and frail, sustained resolution of CLI and preserved ambulatory capacity may decide over independent living and overall prognosis. Despite this importance, previous guidelines have largely ignored follow-up after CLI; arguably because of a striking lack of evidence and because of a widespread assumption that, in the context of CLI, efficacy of initial revascularisation will determine prognosis during the short remaining life expectancy. This chapter of the current CLI guidelines aims to challenge this disposition and to recommend evidentially best clinical practice by critically appraising available evidence in all of the above domains, including antiplatelet and antithrombotic therapy, clinical surveillance, use of duplex ultrasound, and indications for and preferred type of repeat interventions for failing and failed reconstructions. However, as corresponding studies are rarely performed among CLI patients specifically, evidence has to be consulted that derives from expanded patient populations. Therefore, most recommendations are based on extrapolations or subgroup analyses, which leads to an almost systematic degradation of their strength. Endovascular reconstruction and surgical bypass are considered separately, as are specific contexts such as diabetes or renal failure; and critical issues are highlighted throughout to inform future studies.
Subject(s)
Arterial Occlusive Diseases/surgery , Continuity of Patient Care , Ischemia/surgery , Peripheral Vascular Diseases/surgery , Postoperative Complications/prevention & control , Critical Illness , Diabetic Foot/surgery , Exercise Therapy , Humans , Platelet Aggregation Inhibitors/therapeutic use , Practice Guidelines as Topic , Recurrence , Reoperation , Risk Factors , Ultrasonography, Doppler, DuplexABSTRACT
Nowadays the diagnosis of pulmonary embolism (PE) is based on a "diagnostic strategy" rather than a single test. The first step, after identifying patients with suspicion of PE, is to establish the pre-test clinical probability. Several scores are available to make a standardised and reproducible assessment of the clinical probability and these, therefore, represent valuable diagnostic tools. Indeed, it is the clinical probability that guides further investigation. In patients with low or intermediate clinical probability, PE can be safely ruled out by a negative D-dimer in approximately one-third of patients without additional imaging. In the case of a positive D-dimer or high clinical probability, CT pulmonary angiography is now the recommended imaging technique. However, lower limb venous compression ultrasound and ventilation/perfusion scans remain useful in patients with contraindications to CT; mainly those with renal insufficiency. In the presence of readily available and strongly validated diagnostic strategies, the challenge for the future will probably be better identification of patients in whom PE should be suspected.
Subject(s)
Pulmonary Embolism/diagnosis , Algorithms , Biomarkers , Estrogens/adverse effects , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Neoplasms/blood , Neoplasms/complications , Postoperative Complications/diagnosis , Predictive Value of Tests , Pregnancy , Pregnancy Complications, Cardiovascular/diagnosis , Prevalence , Probability , Pulmonary Embolism/blood , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/epidemiology , Radionuclide Imaging , Risk Factors , Severity of Illness Index , Thrombophilia/complications , Thrombophlebitis/diagnostic imaging , Tomography, Spiral Computed , Ultrasonography , Ventilation-Perfusion RatioABSTRACT
BACKGROUND: The risk of recurrence of pulmonary embolism (PE) is higher in men than in women. Differences in clinical presentation of deep vein thrombosis (DVT) have been reported between the two genders but comparative data on PE are lacking. OBJECTIVES: To compare clinical characteristics between women and men with suspected and confirmed PE and their impact on clinical probability prediction scores and on diagnostic work-up of PE, and to assess whether differences at presentation could account for the increased recurrence rate in men. METHODS: Combined data from three prospective cohort studies including a total of 3414 outpatients with suspected PE were analyzed retrospectively. Clinical characteristics, pretest probability of PE, diagnostic yield of non-invasive tests and VTE recurrence rate were compared between genders. RESULTS: The overall prevalence of PE was similar among women and men (22.3% vs. 23.1%; P = 0.55). The clinical probability prediction scores (Geneva score and Wells score) performed equally well in both genders. A non-invasive diagnostic work-up was possible more often in men than in women. The proportion of PE-associated proximal DVT was higher in men than in women (43% vs. 33%; P = 0.009). VTE recurrence rate was also higher in men than women with PE (5.0% vs. 2.3%; P = 0.045). CONCLUSION: In spite of some differences in the clinical presentation of PE between women and men, clinical probability prediction scores perform equally in both genders. A higher prevalence of PE-associated proximal DVT in men could possibly indicate greater severity of PE episodes and partly account for the higher VTE recurrence rate in men.
Subject(s)
Health Status Disparities , Pulmonary Embolism/diagnosis , Venous Thromboembolism/diagnosis , Aged , Biomarkers/blood , Chi-Square Distribution , Europe , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Male , Middle Aged , Multicenter Studies as Topic , Predictive Value of Tests , Prevalence , Pulmonary Embolism/epidemiology , Pulmonary Embolism/etiology , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , Sex Factors , Tomography, X-Ray Computed , Venous Thromboembolism/complications , Venous Thromboembolism/epidemiologyABSTRACT
Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by complete absence of detectable fibrinogen and bleeding symptoms. Many causative mutations have been described to date in all three fibrinogen genes, most of them in the fibrinogen A alpha-chain gene (FGA), but also in the fibrinogen B beta-chain gene (FGB) and the fibrinogen gamma-chain gene (FGG). We report here a novel frameshift mutation (p.Glu262AspfsX158) in FGA exon 5 predicted to lead to a truncated polypeptide with an exceptionally long stretch of abnormal residues identified in homozygosity in a patient with congenital afibrinogenemia. Interestingly, five other frameshift mutations predicted to truncate at the same stop codon have already been described in FGA exon 5.