ALK1 controls hepatic vessel formation, angiodiversity, and angiocrine functions in hereditary hemorrhagic telangiectasia of the liver.

BACKGROUND AND AIMS: In hereditary hemorrhagic telangiectasia (HHT), severe liver vascular malformations are associated with mutations in the Activin A Receptor-Like Type 1 ( ACVRL1 ) gene encoding ALK1, the receptor for bone morphogenetic protein (BMP) 9/BMP10, which regulates blood vessel development. Here, we established an HHT mouse model with exclusive liver involvement and adequate life expectancy to investigate ALK1 signaling in liver vessel formation and metabolic function. APPROACH AND RESULTS: Liver sinusoidal endothelial cell (LSEC)-selective Cre deleter line, Stab2-iCreF3 , was crossed with Acvrl1 -floxed mice to generate LSEC-specific Acvrl1 -deficient mice ( Alk1HEC-KO ). Alk1HEC-KO mice revealed hepatic vascular malformations and increased posthepatic flow, causing right ventricular volume overload. Transcriptomic analyses demonstrated induction of proangiogenic/tip cell gene sets and arterialization of hepatic vessels at the expense of LSEC and central venous identities. Loss of LSEC angiokines Wnt2 , Wnt9b , and R-spondin-3 ( Rspo3 ) led to disruption of metabolic liver zonation in Alk1HEC-KO mice and in liver specimens of patients with HHT. Furthermore, prion-like protein doppel ( Prnd ) and placental growth factor ( Pgf ) were upregulated in Alk1HEC-KO hepatic endothelial cells, representing candidates driving the organ-specific pathogenesis of HHT. In LSEC in vitro , stimulation or inhibition of ALK1 signaling counter-regulated Inhibitors of DNA binding (ID)1-3, known Alk1 transcriptional targets. Stimulation of ALK1 signaling and inhibition of ID1-3 function confirmed regulation of Wnt2 and Rspo3 by the BMP9/ALK1/ID axis. CONCLUSIONS: Hepatic endothelial ALK1 signaling protects from development of vascular malformations preserving organ-specific endothelial differentiation and angiocrine signaling. The long-term surviving Alk1HEC-KO HHT model offers opportunities to develop targeted therapies for this severe disease.

Sex disparities in popliteal artery aneurysms.

OBJECTIVE: Only 5% of patients with popliteal artery aneurysms (PAAs) are female. Evidence on PAA treatment and outcomes in women is therefore scarce. The POPART Registry provides one of Europe's largest data collections regarding PAA treatment. Data on clinical presentation, aneurysm morphology, and perioperative outcomes after open surgical PAA repair in women will be presented. METHODS: POPART is a multicenter, noninterventional registry for open and endovascular PAA repair, with 42 participating centers in Germany and Luxembourg. All patients aged >18 years who have been treated for PAA since 2010 are eligible for study inclusion. Data collection is based on an online electronic case report form. RESULTS: Of the 1236 PAAs, 58 (4.8%) were in women. There were no significant differences in age or cardiopulmonary comorbidities. However, female patients had a lower prevalence of contralateral PAAs and abdominal aortic aneurysms (P < .05). PAAs in women were more likely to be symptomatic before surgery (65.5% vs 49.4%; P = .017), with 19% of women presenting with acute limb ischemia (vs 11%; P = .067). Women had smaller aneurysm diameters than men (22.5 mm vs 27 mm; P = .004) and became symptomatic at smaller diameters (20 mm vs 26 mm; P = .002). Only 8.6% of women and 11.6% of men underwent endovascular aneurysm repair (P > .05); therefore, the perioperative outcome analysis focused on open surgical repair. In total, 23.5% of women and 16.9% of men developed perioperative complications (P > .05). There were no differences in major cardiovascular events (P > .05), but women showed a higher incidence of impaired wound healing (15.7% vs 7.2%; P = .05) and major amputation (5.9% vs 1.1%; P = .027). Female sex was significantly associated with the need for nonvascular reinterventions within 30 days after surgery (odds ratio: 2.48, 95% confidence interval: 1.26-4.88), whereas no significant differences in the odds for vascular reinterventions were observed (odds ratio: 1.98, 95% confidence interval: 0.68-5.77). In the multiple logistic regression model, female sex, symptomatic PAAs, poor quality of outflow vessels, and graft material other than vein graft were independently associated with perioperative reinterventions. CONCLUSIONS: Women have smaller PAAs, are more likely to be symptomatic before treatment, and are more often affected by nonvascular reinterventions in the perioperative course. As our understanding of aneurysmatic diseases in women continues to expand, sex-specific treatment strategies and screening options for women in well-selected cohorts with modified screening protocols should be continuously re-evaluated.

Recent advances in laboratory hematology reflected by a decade of CCLM publications.

On the occasion of the 60th anniversary of Clinical Chemistry and Laboratory Medicine (CCLM) we present a review of recent developments in the discipline of laboratory hematology as these are reflected by papers published in CCLM in the period 2012-2022. Since data on CCLM publications from 1963 to 2012 are also available, we were able to make a comparison between the two periods. This interestingly revealed that the share of laboratory hematology papers has steadily increased and reached now 16% of all papers published in CCLM. It also became evident that blood coagulation and fibrinolysis, erythrocytes, platelets and instrument and method evaluation constituted the 'hottest' topics with regard to number of publications. Some traditional, characteristic CCLM categories like reference intervals, standardization and harmonization, were more stable and probably will remain so in the future. With the advent of important newer topics, like new coagulation assays and drugs and cell population data generated by hematology analyzers, laboratory hematology is anticipated to remain a significant discipline in CCLM publications.

Pilot Study: Magnetic Motion Analysis for Swallowing Detection Using MEMS Cantilever Actuators.

The swallowing process involves complex muscle coordination mechanisms. When alterations in such mechanisms are produced by neurological conditions or diseases, a swallowing disorder known as dysphagia occurs. The instrumental evaluation of dysphagia is currently performed by invasive and experience-dependent techniques. Otherwise, non-invasive magnetic methods have proven to be suitable for various biomedical applications and might also be applicable for an objective swallowing assessment. In this pilot study, we performed a novel approach for deglutition evaluation based on active magnetic motion sensing with permanent magnet cantilever actuators. During the intake of liquids with different consistency, we recorded magnetic signals of relative movements between a stationary sensor and a body-worn actuator on the cricoid cartilage. Our results indicate the detection capability of swallowing-related movements in terms of a characteristic pattern. Consequently, the proposed technique offers the potential for dysphagia screening and biofeedback-based therapies.

[Late Open Semi-conversion with Endograft Preservation for (Type II) Endoleaks with Late Aneurysm Sac Enlargement after EVAR - Indications, Method and Results in Our Own Patient Collective]. / Die späte offene Semikonversion mit Prothesenerhalt bei (Typ II­)Endoleckagen mit spätem Aneurysmasackwachstum nach EVAR - Indikationen, Methode und Ergebnisse im eigenen Patientenkollektiv.

EVAR (endovascular aortic repair) is the most common method for treating an abdominal aortic aneurysm, but according to the latest findings it carries the risk of subsequent complications. These can be caused by (late) aneurysm sac growth. If conservative and surgical therapies fail to treat the aneurysm sac growth, open conversion is necessary to prevent aneurysm rupture. There are several options for open conversion, in which the EVAR prosthesis can be completely preserved or is (partially) removed. Late open semi-conversion with complete in-situ preservation of the EVAR-prosthesis and gathering of the aneurysm sac are a less invasive method than complete conversion and may be performed instead for selected patients. The aim of the present work is to present the surgical method, including indications and technical information, as well as the presentation of the results in our recent patient collective.All patients semi-converted in our department of vascular surgery and phlebology due to (type II) endoleak were included. All data are presented as n (%) or median (range).Between 6/2019 and 3/2023, 13 patients underwent semi-conversion 6 (2-12) years (median, range) after the initial EVAR. The aneurysm sac diameter at the time of semi-conversion was 69 mm (58-95 mm), the operating time was 114 min (97-147 min), the blood loss was 100 ml (100-1500 ml). Five (38%) patients received blood transfusion intraoperatively and 2 (15%) postoperatively. The stay in the intensive care unit lasted 1 (1-5) days, the hospitalisation time was 8 (6-11) days. Postoperative complications were intestinal atony (3 [23%], 1 [8%] with nausea/emesis and gastric tube insertion), anaemia (2 [15%]), hyponatraemia (2 [15%]), delirium (1 [8%]), COVID-19 infection (1 [8%]) and 1 [8%] intra-abdominal postoperative bleeding with the indication for surgical revision and the transfusion of 8 erythrocyte concentrates.Semi-conversion is a safe and practicable surgical method with few severe complications for a selected group of patients, which should be considered as an alternative to more invasive methods with (partial) removal of the EVAR-prosthesis. Further long-term studies comparing semi-conversion to full conversion are needed to demonstrate its benefits.

The unexpected dominance of secondary over primary nucleation.

It is still a challenge to control the formation of particles in industrial crystallization processes. In such processes, new crystals can be generated either by primary or secondary nucleation. While in continuous stirred tank crystallization processes, secondary nucleation is thought to occur due to the shear or attrition of already present larger crystals; in antisolvent crystallization processes, where mixing at the inlets locally causes high supersaturations, primary nucleation is understood to be the main mechanism. We aim to show here that secondary nucleation is the dominant nucleation mechanism, even under conditions that are generally considered to be dominated by primary nucleation mechanisms. Measurements of primary and secondary nucleation rates under similar industrial crystallization conditions of sodium bromate in water, sodium chloride in water, glycine in water and isonicotinamide in ethanol show that the secondary nucleation rate is at least 6 orders of magnitude larger in all these systems. Furthermore, seeded fed-batch and continuous antisolvent crystallizations of sodium bromate under high local supersaturation, seeded with crystals of a specific handedness, result in a close to chirally pure crystalline product with the same handedness. This shows that indeed, enantioselective secondary nucleation is the dominant mechanism in these antisolvent crystallizations. It is even possible to use the enantioselective secondary nucleation mechanism to control the product chirality in such a process, making antisolvent crystallization a viable crystallization-enhanced deracemization technique, having a superior productivity compared to other crystallization-enhanced deracemization methods. Our finding of a dominant secondary nucleation mechanism, rather than primary nucleation, will have a strong impact on nucleation control strategies in industrial crystallization processes.

Quantitative Evaluation for Magnetoelectric Sensor Systems in Biomagnetic Diagnostics.

Dedicated research is currently being conducted on novel thin film magnetoelectric (ME) sensor concepts for medical applications. These concepts enable a contactless magnetic signal acquisition in the presence of large interference fields such as the magnetic field of the Earth and are operational at room temperature. As more and more different ME sensor concepts are accessible to medical applications, the need for comparative quality metrics significantly arises. For a medical application, both the specification of the sensor itself and the specification of the readout scheme must be considered. Therefore, from a medical user's perspective, a system consideration is better suited to specific quantitative measures that consider the sensor readout scheme as well. The corresponding sensor system evaluation should be performed in reproducible measurement conditions (e.g., magnetically, electrically and acoustically shielded environment). Within this contribution, an ME sensor system evaluation scheme will be described and discussed. The quantitative measures will be determined exemplarily for two ME sensors: a resonant ME sensor and an electrically modulated ME sensor. In addition, an application-related signal evaluation scheme will be introduced and exemplified for cardiovascular application. The utilized prototype signal is based on a magnetocardiogram (MCG), which was recorded with a superconducting quantum-interference device. As a potential figure of merit for a quantitative signal assessment, an application specific capacity (ASC) is introduced. In conclusion, this contribution highlights metrics for the quantitative characterization of ME sensor systems and their resulting output signals in biomagnetism. Finally, different ASC values and signal-to-noise ratios (SNRs) could be clearly presented for the resonant ME sensor (SNR: -90 dB, ASC: 9.8×10-7 dB Hz) and also the electrically modulated ME sensor (SNR: -11 dB, ASC: 23 dB Hz), showing that the electrically modulated ME sensor is better suited for a possible MCG application under ideal conditions. The presented approach is transferable to other magnetic sensors and applications.

Active Magnetoelectric Motion Sensing: Examining Performance Metrics with an Experimental Setup.

Magnetoelectric (ME) sensors with a form factor of a few millimeters offer a comparatively low magnetic noise density of a few pT/Hz in a narrow frequency band near the first bending mode. While a high resonance frequency (kHz range) and limited bandwidth present a challenge to biomagnetic measurements, they can potentially be exploited in indirect sensing of non-magnetic quantities, where artificial magnetic sources are applicable. In this paper, we present the novel concept of an active magnetic motion sensing system optimized for ME sensors. Based on the signal chain, we investigated and quantified key drivers of the signal-to-noise ratio (SNR), which is closely related to sensor noise and bandwidth. These considerations were demonstrated by corresponding measurements in a simplified one-dimensional motion setup. Accordingly, we introduced a customized filter structure that enables a flexible bandwidth selection as well as a frequency-based separation of multiple artificial sources. Both design goals target the prospective application of ME sensors in medical movement analysis, where a multitude of distributed sensors and sources might be applied.

The prospective GermanVasc cohort study.

Background: Previous observational studies reported a wide variation and possible room for improvement in the treatment of patients suffering from symptomatic peripheral artery disease (PAD). Yet, systematic assessment of everyday clinical practice is lacking. A General Data Protection Regulation (GDPR) compliant registry was developed and used to collect comprehensive data on clinical treatment and outcomes regarding PAD in Germany. Here, we report baseline characteristics of patients prospectively enrolled until the end of 2020. Methods: The GermanVasc registry study is a prospective longitudinal multicentre cohort study. Between 1st May 2018 and 31st December 2020, invasive endovascular, open-surgical, and hybrid revascularisations of patients suffering from chronic symptomatic PAD were prospectively included after explicit informed consent (NCT03098290). For ensuring high quality of the data, we performed comprehensive risk-based and random-sample external and internal validation. Results: In total, 5608 patients from 31 study centres were included (34% females, median 69 years). On-site monitoring visits were performed at least once in all centres. The proportion of chronic limb-threatening ischaemia was 30% and 13% were emergent admissions. 55% exhibited a previous revascularisation. Endovascular techniques made 69% among all documented invasive procedures (n=6449). Thirty-five percent were classified as patients with severe systemic disease, and 3% exhibited a constant threat to life according to the American Society of Anaesthesiologists classification. The risk profile comprised of 75% former or current smokers, 36% diabetes mellitus, and in 30% a current ischemic heart disease was present. At discharge, 93% of the patients received antiplatelets and 77% received statins. Conclusions: The GermanVasc registry study provides insights into real-world practice of treatment and outcomes of 5,608 patients with symptomatic PAD in Germany. The cohort covers a broader range of disease severity and types of interventions than usually found in trials. In future studies, comparative outcomes will be analysed in more detail.

Basophil counting in hematology analyzers: time to discontinue?

Basophils (basophilic granulocytes) are the least abundant cells in blood. Nowadays, basophils are included in the complete blood count performed by hematology analyzers and therefore reported in practically all patients in whom hematologic investigations are requested. However, hematology analyzers are not reliable enough to report clinically useful results. This is due to a combination of very high analytical imprecision and poor specificity, because the chemical and physical methods used for basophil counting in hematology analyzers are ill-defined and thus basophils are not well recognized by the analyzers. As a result, false basophil counts are quite common. In view of increasing analytical performance demands, hematology laboratories should stop reporting basophil counts produced by hematology analyzers. Suggestions for alternative pathways are presented for those situations where basophils are of clinical relevance.

Role of RDW in mathematical formulas aiding the differential diagnosis of microcytic anemia.

Many mathematical formulas containing simple red blood cell parameters have been proposed for differentiating between iron deficiency and thalassemia in patients with microcytic anemia. Approximately half of these formulas do include red cell distribution width (RDW), along with other red cell parameters. In the present study we investigated the role of RDW, expressed in relative or in absolute units in relation with the formulas' discriminant performance. We used a database containing over 2200 subjects with microcytic anemia, for whom a final diagnosis (iron-deficiency anemia, thalassemia, both or other) was available. Performance of the discriminant formulas was assessed by Receiver Operator Curve analysis. Substitution of relative by absolute RDW resulted in statistically significant performance increase (area under the ROC curve) in 16 out of 23 formulas, predominantly due to increased specificity. Relevant performance deterioration was seen in only three formulas that had low initial performance already with the original relative RDW. For optimal differential diagnostic performance, an RDW-based formula for distinguishing thalassemia from iron-deficiency anemia in microcytic anemia should contain 'absolute' instead of relative RDW.

Multicenter performance evaluation of the Abbott Alinity hq hematology analyzer.

Background Alinity hq (Abbott) is a new high-throughput hematology analyzer that exclusively employs optical principles for detecting and enumerating blood cells. It reports 29 parameters, including a six-part white blood cell (WBC) differential. The aim of this multicenter study was to evaluate the analytical and clinical performance of the Alinity hq. Methods Complete blood count (CBC) results and morphological flagging were compared to that of CELL-DYN Sapphire (Abbott) and 2 × 200-cell manual differential results, on 1473 whole-blood samples from a well-defined patient population from three different clinical laboratories in the Netherlands. In addition, within-run and within-laboratory precision, linearity, limit of quantitation, carryover and sample stability were assessed. External quality assessment samples were also evaluated. Results Data analysis demonstrated strong concordance of Alinity hq results with those of CELL-DYN Sapphire for all CBC parameters, except for basophil granulocytes. Alinity hq WBC differential showed high level of agreement with manual differential results and exhibited a better agreement with manual basophil results than CELL-DYN Sapphire. The sensitivity of the Alinity hq Blast flag was 57.6%, equal to the 57.6% sensitivity of the CELL-DYN Sapphire's Blast Alert. When considering samples with ≥5% blasts, the sensitivity of the Alinity hq Blast flag was 70.0%. Analytical performance of Alinity hq was shown to be consistent with state-of-the-art (SOTA) performance characteristics. Conclusions Alinity hq CBC measurands demonstrated good overall agreement with results obtained with CELL-DYN Sapphire, as well as manual WBC differential. The analytical and clinical performance characteristics of Alinity hq make it well suited for clinical laboratories.

Assessment of iron-restricted erythropoiesis in chronic renal disease: evaluation of Abbott CELL-DYN Sapphire mean reticulocyte hemoglobin content (MCHr).

We studied the performance of mean reticulocyte hemoglobin content (MCHr), measured on Abbott CELL-DYN Sapphire analyzer for the detection of functional iron deficiency. Patients with anemia and with renal disease were prospectively selected from the outpatient population of our hospital, 512 subjects were studied. Diagnoses and other medical data were retrieved from the hospital information system. MCHr was measured using a CELL-DYN Sapphire hematology analyzer (Abbott Diagnostics). Standard laboratory and statistical tests were used. Receiver operating characteristic (ROC) analysis was used to establish the diagnostic performance of MCHr for detecting iron-restricted erythropoiesis, with transferrin saturation <20% as the gold standard. Patients in the iron deficiency anemia group all had a state of iron depletion and iron-restricted erythropoiesis (median MCHr 25.4 pg). Patients with anemia of chronic disease showed also low MCHr, median 27.6 pg, but not statistically different from the iron deficient group (p = .0585). Renal patients with iron restriction (n = 66) had significantly lower MCHr (p < .0001) than those receiving adequate iron supply (n = 100): median MCHr were 27.9 and 32.5 pg, respectively. ROC analysis gave sensitivity 84.4% and specificity 80.1% with area under curve 0.863 (95% CI 0.823-0.902) at an MCHr cut-off 30.0 pg. MCHr on CELL-DYN Sapphire has equivalent clinical performance for detecting absolute or functional iron deficiency in patients with chronic kidney disease as previously published for another type of analyzer.

Comparative evaluation of platelet counts in two hematology analyzers and potential effects on prophylactic platelet transfusion decisions.

BACKGROUND: Decisions on prophylactic platelet (PLT) transfusions are generally based on the recipient's PLT count, but few clinicians are aware of precision and accuracy of the PLT counting methods used by the clinical laboratory. Each PLT counting technology has its specific inaccuracy, especially in thrombocytopenic samples and therefore may impact decisions on PLT transfusions. STUDY DESIGN AND METHODS: Five routine PLT counting methods available in two hematology analyzers (Sysmex XN-2000 and Abbott CELL-DYN Sapphire) were investigated (impedance and optical on both analyzers and fluorescent on XN-2000), using the CD61 immunologic PLT method as a reference. The impact of counting inaccuracy on imaginary transfusion decisions was examined at various common PLT thresholds. RESULTS: In total 341 samples were analyzed, 178 of which had PLT counts of less than 35 × 109 /L. Despite excellent overall correlation with the reference method (r > 0.99), thrombocytopenic samples showed only modest correlation for impedance and XN-2000 optical methods. Sapphire optical and XN-2000 fluorescent methods correlated very well with the reference, albeit with bias in the very low range. We noticed potential risk of undertransfusion (ranging from 2% to 90%), depending on the threshold used. The risk of overtransfusion was small (<10%). CONCLUSIONS: The XN-2000 fluorescent PLT counting method showed excellent correlation with the CD61 reference count, closely followed by the CELL-DYN Sapphire optical method. XN-2000 impedance and optical and Sapphire impedance methods are not accurate enough for basing transfusion decisions on. Only XN-2000 fluorescent, Sapphire optical, and CD61 methods are sufficiently accurate for making appropriate clinical decisions in patients with severe thrombocytopenia.

Critical appraisal of discriminant formulas for distinguishing thalassemia from iron deficiency in patients with microcytic anemia.

BACKGROUND: Many discriminant formulas have been reported for distinguishing thalassemia trait from iron deficiency in patients with microcytic anemia. Independent verification of several discriminant formulas is deficient or even lacking. Therefore, we have retrospectively investigated discriminant formulas in a large, well-characterized patient population. METHODS: The investigational population consisted of 2664 patients with microcytic anemia: 1259 had iron deficiency, 1196 'pure' thalassemia trait (877 ß- and 319 α-thalassemia), 150 had thalassemia trait with concomitant iron deficiency or anemia of chronic disease, and 36 had other diseases. We investigated 25 discriminant formulas that only use hematologic parameters available on all analyzers; formulas with more advanced parameters were disregarded. The diagnostic performance was investigated using ROC analysis. RESULTS: The three best performing formulas were the Jayabose (RDW index), Janel (11T), and Green and King formulas. The differences between them were not statistically significant (p>0.333), but each of them had significantly higher area under the ROC curve than any other formula. The Jayabose and Green and King formulas had the highest sensitivities: 0.917 both. The highest specificity, 0.925, was found for the Janel formula, which is a composite score of 11 other formulas. All investigated formulas performed significantly better in distinguishing ß- than α-thalassemia from iron deficiency. CONCLUSIONS: In our patient population, the Jayabose RDW index, the Green and King formula and the Janel 11T score are superior to all other formulas examined for distinguishing between thalassemia trait and iron deficiency anemia. We confirmed that all formulas perform much better in ß- than in α-thalassemia carriers and also that they incorrectly classify approximately 30% of thalassemia carriers with concomitant other anemia as not having thalassemia. The diagnostic performance of even the best formulas is not high enough for making a final thalassemia diagnosis, but in countries with limited resources, they can be helpful in identifying those patients who need further examinations for genetic anemia.

Adductor Canal Compression Syndrome in a 46-Year-Old Female Patient Leading to Acute External Iliac, Femoral, and Popliteal Artery Thrombosis and Critical Ischemia: A Case Report.

The adductor canal compression syndrome is one of the several rare nontraumatic causes of arterial occlusions, which may lead to critical ischemia of the lower limb. We report the case of a 46-year-old athletic woman, who suffered from activity-related paresthesia and sharp pain in the left upper and lower leg for 2 years. Imaging and neurological investigations of the spine remained without pathological findings that would explain the patient's complaints. Actually, the patient presented with symptoms of critical lower limb ischemia. Magnetic resonance angiography revealed nearly complete thrombotic occlusion of the common femoral artery and the arteries of the lower leg. An emergency surgery was performed, revealing an external compression of the superficial femoral artery in the adductor canal. Subsequently, a thrombectomy was performed and a venous bypass graft was installed. No postoperative complications occurred, the patient recovered well and could return to her activities of daily living about 3 weeks after the surgery. The adductor canal compression syndrome results from a local anomalous musculotendinous band or hypertrophic musculature surrounding the passing structures. It mainly occurs in athletes exposed to repetitive stress, especially runners and skiers, and may lead to thrombosis followed by critical lower extremity ischemia. The lack of obvious symptoms during routine physical examination often impedes rapid diagnosis and timely therapy. Considering the high thrombotic risk, attention should be paid to this rare cause of lower limb pain to prevent the patient from critical lower extremity ischemia and potential limb loss due to consecutive acute thrombotic occlusions.

Konsensuspapier zur symptomorientierten Therapie der chronischen Venenerkrankungen.

HINTERGRUND: Chronische Venenerkrankungen sind eine Volkskrankheit. Venöse Symptome wie Schwellungs- und Schweregefühl können bereits früh ohne sichtbaren Befund auftreten und werden als belastend erlebt. Ein Fortschreiten im Sinne einer objektivierbaren Varikose bzw. chronischen venösen Insuffizienz schränkt die Lebensqualität erheblich ein. METHODIK: Pubmed-gelistete Publikationen sowie relevante Leitlinien zur Therapie chronischer Venenkrankheiten bilden die Basis der vorliegenden Konsensusempfehlungen. Inkludiert in die Bewertung wurden ausschließlich aussagekräftige randomisierte Studien (RCT) und Übersichtsarbeiten (Reviews/Metaanalysen). ERGEBNISSE: Die symptomorientierte Behandlung chronischer Venenerkrankungen stützt sich auf drei Säulen mit nachgewiesener Wirksamkeit: invasive Therapie, Kompressionstherapie und orale medikamentöse Therapie. Gemäß Empfehlungen aktueller Leitlinien sollte zunächst eine Sanierung des venösen Gefäßbetts erwogen werden, um einen störungsfreien venösen Blutfluss wiederherzustellen und Symptome und pathologische Veränderungen zu beseitigen oder zu bessern. Ist ein invasiver Eingriff nicht möglich bzw. nicht erwünscht oder bestehen nach einem Eingriff noch Restsymptome, gilt es, die symptomatischen Therapieoptionen optimal auszuschöpfen. Kompressionstherapie und medikamentöse Therapie können allein oder in Kombination angewendet werden. Welche Strategie den größten Erfolg verspricht, ist individuell zu entscheiden. SCHLUSSFOLGERUNGEN: Chronische Venenerkrankungen sollten auf der Basis der individuellen pathophysiologischen Störung behandelt werden. Sie symptomorientierte Behandlung chronischer Venenerkrankungen fußt auf der invasiven Therapie, der Kompressionstherapie und der medikamentösen Therapie. Bei der Indikationsstellung sind objektive Symptome ebenso wie subjektive Beschwerden zu berücksichtigen.

Consensus statement on the symptom-based treatment of chronic venous diseases.

BACKGROUND: Chronic venous diseases are very common. Early symptoms such as a sensation of swelling and heaviness may occur without objectifiable findings, but are nevertheless perceived as bothersome. Progressive disease - marked by varicose veins and symptoms of chronic venous insufficiency - is associated with considerable impairment in quality of life. METHODS: The present consensus recommendations are based on publications in Pubmed-listed journals as well as relevant international therapeutic guidelines on chronic venous diseases. Only conclusive randomized controlled trials (RCTs) and review articles/meta-analyses were included. RESULTS: Symptom-based treatment of chronic venous diseases is based on three therapeutic pillars with proven efficacy: invasive therapy, compression therapy, and oral pharmacological treatment. According to current therapeutic guidelines, invasive procedures aimed at restoring unimpaired venous blood flow as well as improving or eliminating pathological changes should be the first-line approach. If an invasive approach is infeasible or undesirable, or if symptoms persist following a therapeutic intervention, optimal use of symptom-based treatment options is recommended. Compression and pharmacological therapy may each be used as sole treatment or in combination. To guarantee maximum therapeutic success, individual treatment decisions should be made on a case-by-case basis. CONCLUSIONS: Chronic venous diseases should be treated on the basis of individual pathophysiological disturbances. Symptom-based treatment of chronic venous disorders encompasses invasive therapy, compression therapy, and oral pharmacological therapy. Considerations in choosing the appropriate treatment option should include both objective signs as well as subjective symptoms.

Discriminant indices for distinguishing thalassemia and iron deficiency in patients with microcytic anemia: a meta-analysis.

BACKGROUND: More than 40 mathematical indices have been proposed in the hematological literature for discriminating between iron deficiency anemia and thalassemia trait in subjects with microcytic red blood cells (RBCs). None of these discriminant indices is 100% sensitive and specific and also the ranking of the discriminant indices is not consistent. Therefore, we decided to conduct the first meta-analysis of the most frequently used discriminant indices. METHODS: An extensive literature search yielded 99 articles dealing with 12 indices that were investigated five or more times. For each discriminant index we calculated the diagnostic odds ratio (DOR) and summary ROC analysis was done for comparing the performance of the indices. RESULTS: The ratio of microcytic to hypochromic RBCs (M/H ratio) showed the best performance, DOR=100.8. This was significantly higher than that of all other indices investigated. The RBC index scored second (DOR=47.0), closely followed by the Sirdah index (DOR=46.7) and the Ehsani index (DOR=44.7). Subsequently, there was a group of four indices with intermediate and three with lower DOR. The lowest performance (DOR=6.8) was found for the RDW (Bessman index). Overall, the indices performed better for adults than for children. CONCLUSIONS: The M/H ratio outperformed all other discriminant indices for discriminating between iron deficiency anemia and thalassemia trait. Although its sensitivity and specificity are not high enough for making a definitive diagnosis, it is certainly of value for identifying those subjects with microcytic RBC in whom diagnostic tests for confirming thalassemia are indicated.