Technical Indicators to Evaluate the Degree of Large Clot Formation Inside the Membrane Fiber Bundle of an Oxygenator in an In Vitro Setup

The most common technical complication during ECMO is clot formation. A large clot inside a membrane oxygenator reduces effective membrane surface area and therefore gas transfer capabilities, and restricts blood flow through the device, resulting in an increased membrane oxygenator pressure drop (dpMO). The reasons for thrombotic events are manifold and highly patient specific. Thrombus formation inside the oxygenator during ECMO is usually unpredictable and remains an unsolved problem. Clot sizes and positions are well documented in literature for the Maquet Quadrox‐i Adult oxygenator based on CT data extracted from devices after patient treatment. Based on this data, the present study was designed to investigate the effects of large clots on purely technical parameters, for example, dpMO and gas transfer. Therefore, medical grade silicone was injected into the fiber bundle of the devices to replicate large clot positions and sizes. A total of six devices were tested in vitro with silicone clot volumes of 0, 30, 40, 50, 65, and 85 mL in accordance with ISO 7199. Gas transfer was measured by sampling blood pre and post device, as well as by sampling the exhaust gas at the devices’ outlet at blood flow rates of 0.5, 2.5, and 5.0 L/min. Pre and post device pressure was monitored to calculate the dpMO at the different blood flow rates. The dpMO was found to be a reliable parameter to indicate a large clot only in already advanced “clotting stages.” The CO₂ concentration in the exhaust gas, however, was found to be sensitive to even small clot sizes and at low blood flows. Exhaust gas CO₂ concentration can be monitored continuously and without any risks for the patient during ECMO therapy to provide additional information on the endurance of the oxygenator. This may help detect a clot formation and growth inside a membrane oxygenator during ECMO even if the increase in dpMO remains moderate.     

Diagnosis of Heerfordt's syndrome by state-of-the-art ultrasound in combination with parotid biopsy: a case report

The parotid gland is rarely affected by sarcoidosis (6% of all cases). If there is initial parotitis, and other major symptoms include fever, uveitis, or facial paralysis, the condition is referred to as Heerfordt's syndrome. The case presented here describes the diagnostic work-up and differentiation of swelling of the parotid gland by employing state-of-the-art ultrasound techniques in a 33-year-old patient with Heerfordt's syndrome. Color-coded duplex ultrasound demonstrated hypervascularization. Tissue harmonic and photopic imaging ultrasound additionally depicted hypoechoic, septated structural lesions of the glandular parenchyma with an optimized contrast. Since such structural changes are not a specific sonographic criterion for sarcoidosis, ultrasound-guided biopsy was performed for further clarification of the etiology of parotitis and for excluding lymphoma. In conclusion, state-of-the-art ultrasound with the option of obtaining a biopsy at low risk is a useful procedure for diagnosing unclear pathology of the parotid gland with rapid histological confirmation.     

Is impingement the cause of jumper's knee? Dynamic and static magnetic resonance imaging of patellar tendinitis in an open-configuration system

BACKGROUND: Chronic overload is considered the main cause of patellar tendinitis, but it has been postulated that impingement of the inferior patellar pole against the patellar tendon during knee flexion could be responsible. HYPOTHESIS: The role of the patellar pole in patellar tendinitis can be determined by dynamic magnetic resonance imaging. STUDY DESIGN: Case-control study. METHODS: We compared 19 knees with patellar tendinitis and 32 asymptomatic knees of age-matched subjects using an open-configuration magnetic resonance imaging system. Dynamic sagittal images were obtained from full extension to 100 degrees of flexion with and without activation of the quadriceps muscle. The following measurements were made from the images: tendon-patella angle, anteroposterior diameter of the tendon, signal difference-to-noise ratio, the shape of the inferior patellar pole, and the location of the patellar tendon insertion. RESULTS: The tendon-patella angle was not significantly different between groups at any flexion angle, with or without quadriceps muscle activation. The insertion site of the patellar tendon differed significantly but not the shape of the inferior pole of the patella. The volume and the signal difference-to-noise ratio of zones of increased intratendinous signal as well as the anteroposterior diameter of the proximal patellar tendon were increased in symptomatic knees. CONCLUSIONS: The relationship between the patella and the patellar tendon was identical in both groups; therefore, chronic overload seems to be a major cause of patellar tendinitis.     

A non-randomized controlled clinical trial on autologous chondrocyte implantation (ACI) in cartilage defects of the medial femoral condyle with or without high tibial osteotomy in patients with varus deformity of less than 5°

Purpose

High tibial osteotomy (HTO) is a recommended concomitant surgery when treating cartilage lesions of the medial femoral condyle (MFC). Varus deformities of 5° and more were considered an indication for HTO in patients with cartilage defects. This study compares clinical outcome in patients with ACI and concomitant varus deformity of <5° with or without additional HTO.

Methods

43 patients with isolated cartilage defect of the MFC and varus deformity between 1° and 5° (mean age 39.14 ± 8.35 years; mean varus deformity 2.84 ± 1.19°) were included (follow-up 71.88 ± 23.99 months). Group A (n = 19) was treated with ACI and additional HTO; group B (n = 24) received ACI only. Survival rate in terms of absence of the need of reintervention was defined as main outcome parameter. In the subgroup without reintervention, functional outcome (KOOS and WOMAC) was evaluated.

Results

Overall rate of reintervention was 12 (27.9 %). Survival was significantly higher in group A (group A 89.5 %, group B 58.33 %; p = 0.023). Although a trend for better clinical outcome was observed for group A in the subgroup without reintervention, this observation lacked statistical significance (KOOS_symptoms group A 73.23, group B 59.64; p = 0.274).

Conclusion

While there is general consensus for treating varus deformities of >5° in patients with cartilage lesions of the medial femoral condyle, HTO also leads to a reduced rate of reinterventions and longer survival rates in patients with varus deformities of <5°.     

Rating scales for behavioral symptoms in Huntington's disease: Critique and recommendations

Behavioral symptoms are an important feature of Huntington's disease and contribute to impairment in quality of life. The Movement Disorder Society commissioned the assessment of the clinimetric properties of rating scales in Huntington's disease to make recommendations regarding their use, following previously used standardized criteria. A systematic literature search was conducted to identify the scales used to assess behavioral symptoms in Huntington's disease. For the purpose of this review, 7 behavioral domains were deemed significant in Huntington's disease: irritability, anxiety, depression, apathy, obsessive‐compulsive behaviors, psychosis, and suicidal ideation. We included a total of 27 behavioral rating scales, 19 of which were of a single behavioral domain and the remaining 8 scales included multiple behavioral domains. Three rating scales were classified as “recommended” exclusively for screening purposes: the Irritability Scale for irritability, the Beck Depression Inventory‐II, and the Hospital Anxiety and Depression Scale for depression. There were no “recommended” scales for other purposes such as diagnosis, severity, or change in time or to treatment. The main challenges identified for assessment of behavioral symptoms in Huntington's disease are the co‐occurrence of multiple behavioral symptoms, the particular features of a behavioral symptom in Huntington's disease, and the need to address stage‐ and disease‐specific features, including cognitive impairment and lack of insight. The committee concluded that there is a need to further validate currently available behavioral rating scales in Huntington's disease to address gaps in scale validation for specific behavioral domains and purpose of use. © 2016 International Parkinson and Movement Disorder Society     

Interleukin-7 levels in synovial fluid increase with age and MMP-1 levels decrease with progression of osteoarthritis

Background and purpose

Little is known about biochemical mediators that correlate with the initiation and progression of knee osteoarthritis (OA). We therefore valuated the roles of cytokines and metalloenzymes in knee OA in relation to OA grading, age, and BMI.

Patients and methods

A multiplex ELISA-based immunoassay (Luminex technology) was used to measure biochemical mediators in the synovial fluid (SF) of 82 patients undergoing knee surgery. All patients were classified according to age, BMI, and OA grade. 24 patients had no signs of OA (knee reconstruction surgeries). The mediators that were tested for included interleukins (IL-1Ra, IL-6, IL-7, and IL-18), chemokines (CCL2 (MCP-1), CCL3 (MIP-1a), and CXCL8 (IL-8)), growth factors (HGF and VEGF), and matrix metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-13).

Results

There was a correlation between IL-7 levels in SF and age (p < 0.01). The 11 highest IL-7 levels were seen in patients who were aged between 59 and 72 but had different OA grades. In contrast, all patients who had severe OA in all 3 knee compartments (pan-OA) had only low or medium IL-7 levels. There was a negative correlation between MMP-1 levels in synovial fluid and grade of OA (p < 0.001). Correlation studies between pairs of mediators revealed two groups of mediators that are important in OA progression, dominated by MCP-1 and IL-1Ra.

Interpretation

IL-7 levels in SF are elevated in elderly people suffering from OA of different grades, but they are depressed in patients with severe 3-compartment OA, possibly due to widely impaired chondrocytes embedded in the affected cartilage tissue. The observed decrease in MMP-1 levels in SF, which is dependent on the severity of OA, may be caused by deterioration of superficial cartilage layers during progression of OA.

List of abbreviations

BMI

body mass index

CCL

chemokine (C-C motif) ligand

CXCL

chemokine (C-X-C motif) ligand

HGF

hepatocyte growth factor

ICRS

International Cartilage Repair Society

IL

interleukin

IL-1Ra

IL-1 receptor antagonist

MCP

monocyte chemoattractant protein

MIP

macrophage inflammatory protein

MMP

matrix metalloproteinase

OA

osteoarthritis

SF

synovial fluid

VEGF

vascular endothelial growth factor

Progression of knee OA is often driven by biomechanical forces (Englund 2010), whereas the etiology of OA in other joints is less affected by mechanical stress. Biochemical mediators such as cytokines, growth factors, and matrix metalloproteinases—acting individually or in networks—profoundly influence cellular responses in joint tissues, modifying both catabolic and anabolic activities involved in the pathogenesis of OA (Goldring and Goldring 2007). Ageing is the most prominent risk factor for OA, and chondrocyte senescence and aging-related changes in the matrix, such as articular surface fibrillation and proteoglycan changes, are most likely to contribute to joint ageing (Martin and Buckwalter 2002, Shane Anderson and Loeser 2010). However, despite intensive research efforts, little is known about biochemical factors whose levels may correlate with the severity of knee OA (Belo et al. 2007). Also, age-related changes in cytokine production in body fluids have not been investigated completely (Gardner and Murasko 2002).Biochemical mediators found in synovial fluid (SF) that affect the cellular functions of tissues of the knee joint include interleukins (ILs), chemokines, growth factors, and matrix metalloproteinases (MMPs). Interleukins, both pro- and anti-inflammatory, have a pivotal role in arthritic diseases and are potential targets of OA therapy. Chemokines, which are small, chemoattractant cytokines, have key roles in the accumulation of inflammatory cells at the site of inflammation. Growth factors produced by chondrocytes and subchondral bone regulate the growth of blood vessels in the joint. Some recent studies have supported the notion that inhibition of abnormal angiogenesis will provide effective therapeutic strategies for treatment of OA (Ashraf and Walsh 2008). MMPs and pro-inflammatory cytokines are involved in a collagen II-dependent feed-forward mechanism of matrix degradation in human articular cartilage (Klatt et al. 2009).To improve our understanding of the molecular and cellular processes involved in joint ageing and in the initiation and progression of OA, we wanted to determine the levels of biochemical mediators that correlate with the severity of knee OA or patient age.     

Failed Arthroscopic Repair of a Large Reverse Hill-Sachs Lesion Using Bone Allograft and Cannulated Screws: A Case Report

Anterior impression fractures of the humeral head (reverse Hill-Sachs lesions) are typical concomitant bony injuries of posterior shoulder dislocations. When more than 20% of the humeral articulating surface is affected, surgical treatment is required, typically necessitating open surgery. Recently, cases of successful arthroscopic treatment of small reverse Hill-Sachs lesions involving less than 30% of the articulating surface have been reported. This article presents a case of a large reverse Hill-Sachs lesion affecting over 40% of the articulating surface that was treated arthroscopically by retrograde elevation, bone allografting, and cannulated screw insertion. The postoperative radiographic images showed a successful reduction of the impacted articulating surface of the humeral head. However, at 6 months' follow-up, the patient presented with pain and symptoms of a frozen shoulder. Cross-sectional imaging showed necrosis, partial absorption, and loss of reduction of the formerly elevated segment requiring humeral head replacement. This case report shows that even though the arthroscopic retrograde elevation of large reverse Hill-Sachs lesions is technically achievable, the outcome can be unsatisfactory because of the limitations in biologic healing response associated with large lesions of the humeral articulating surface.     

A Coupled Approach for Fluid Dynamic Problems Using the PDE Framework Peano

We couple different flow models, i.e. a finite element solver for the Navier-Stokes equations and a Lattice Boltzmann automaton, using the framework Peano as a common base. The new coupling strategy between the meso- and macroscopic solver is presented and validated in a 2D channel flow scenario. The results are in good agreement with theory and results obtained in similar works by Latt et al. In addition, the test scenarios show an improved stability of the coupled method compared to pure Lattice Boltzmann simulations.     

Role of iron deficiency and anemia in cardio-renal syndromes

Chronic heart failure is a common disorder associated with unacceptably high mortality rates. Chronic renal disease and anemia are two important comorbidities that significantly influence morbidity and mortality in patients with chronic heart failure (CHF). Progress in CHF again may cause worsening of kidney function and anemia. To describe this vicious cycle, the term cardio-renal anemia syndrome has been suggested. Iron deficiency is part of the pathophysiology of anemia in both CHF and chronic kidney disease, which makes it an interesting target for treatment of anemia in cardio-renal anemia syndrome. Recently, studies have highlighted the potential clinical benefits of treating iron deficiency in patients with CHF, even if these patients are nonanemic. This article summarizes studies investigating the influence of iron deficiency with or without anemia in chronic kidney disease and CHF and gives an overview of preparations of intravenous iron currently available.     

Podocyte EphB4 signaling helps recovery from glomerular injury

Eph receptor tyrosine kinases and their ligands (ephrins) have a pivotal role in the homeostasis of many adult organs and are widely expressed in the kidney. Glomerular diseases beginning with mesangiolysis can recover, with podocytes having a critical role in this healing process. We studied here the role of Eph signaling in glomerular disease recovery following mesangiolytic Thy1.1 nephritis in rats. EphB4 and ephrinBs were expressed in healthy glomerular podocytes and were upregulated during Thy1.1 nephritis, with EphB4 strongly phosphorylated around day 9. Treatment with NPV-BHG712, an inhibitor of EphB4 phosphorylation, did not cause glomerular changes in control animals. Nephritic animals treated with vehicle did not have morphological evidence of podocyte injury or loss; however, application of this inhibitor to nephritic rats induced glomerular microaneurysms, podocyte damage, and loss. Prolonged NPV-BHG712 treatment resulted in increased albuminuria and dysregulated mesangial recovery. Additionally, NPV-BHG712 inhibited capillary repair by intussusceptive angiogenesis (an alternative to sprouting angiogenesis), indicating a previously unrecognized role of podocytes in regulating intussusceptive vessel splitting. Thus, our results identify EphB4 signaling as a pathway allowing podocytes to survive transient capillary collapse during glomerular disease.