FGF2 overrides key pro-fibrotic features of bone marrow stromal cells isolated from Modic type 1 change patients.

Extensive extracellular matrix production and increased cell-matrix adhesion by bone marrow stromal cells (BMSCs) are hallmarks of fibrotic alterations in the vertebral bone marrow known as Modic type 1 changes (MC1). MC1 are associated with non-specific chronic low-back pain. To identify treatment targets for MC1, in vitro studies using patient BMSCs are important to reveal pathological mechanisms. For the culture of BMSCs, fibroblast growth factor 2 (FGF2) is widely used. However, FGF2 has been shown to suppress matrix synthesis in various stromal cell populations. The aim of the present study was to investigate whether FGF2 affected the in vitro study of the fibrotic pathomechanisms of MC1-derived BMSCs. Transcriptomic changes and changes in cell-matrix adhesion of MC1-derived BMSCs were compared to intra-patient control BMSCs in response to FGF2. RNA sequencing and quantitative real-time polymerase chain reaction revealed that pro-fibrotic genes and pathways were not detectable in MC1-derived BMSCs when cultured in the presence of FGF2. In addition, significantly increased cell-matrix adhesion of MC1-derived BMSCs was abolished in the presence of FGF2. In conclusion, the data demonstrated that FGF2 overrides key pro-fibrotic features of MC1 BMSCs in vitro. Usage of FGF2-supplemented media in studies of fibrotic mechanisms should be critically evaluated as it could override normally dominant biological and biophysical cues.

Water-window high harmonic generation with 0.8-µm and 2.2-µm OPCPAs at 100 kHz.

We compare the generation of high-order harmonics in the water window (283-543 eV) with 0.8-µm and 2.2-µm few-cycle lasers at a pulse repetition rate of 100 kHz. Using conventional phase matching with the 2.2-µm driver and what we attribute to nonadiabatic self-phase-matching with the 0.8-µm driver, photons up to 0.6 keV (2 nm) are generated in both cases. Special attention is paid to the understanding of the generation mechanism with the 0.8-µm laser amplifier system. We use the same beamline and pump laser for both drivers, which allows for a direct flux comparison at the two driving wavelengths. For photon energies around 280 eV, a 10-100 times higher flux is obtained from the 2.2-µm versus the 0.8-µm laser system in helium and neon. The crossover at which the 2.2-µm yields a higher flux compared to the 0.8-µm driver is found to be as high as 0.2 keV. Our study supports the common approach of using long-wavelength lasers in a phase-matched regime for efficient generation of water-window harmonics, but also shows that the more widespread 0.8-µm wavelength can be used to generate water-window harmonics with an efficiency close to the one of a less common 2.2-µm source.

Pro-fibrotic phenotype of bone marrow stromal cells in Modic type 1 changes.

Modic type 1 changes (MC1) are painful vertebral bone marrow lesions frequently found in patients suffering from chronic low-back pain. Marrow fibrosis is a hallmark of MC1. Bone marrow stromal cells (BMSCs) are key players in other fibrotic bone marrow pathologies, yet their role in MC1 is unknown. The present study aimed to characterise MC1 BMSCs and hypothesised a pro-fibrotic role of BMSCs in MC1. BMSCs were isolated from patients undergoing lumbar spinal fusion from MC1 and adjacent control vertebrae. Frequency of colony-forming unit fibroblast (CFU-F), expression of stem cell surface markers, differentiation capacity, transcriptome, matrix adhesion, cell contractility as well as expression of pro-collagen type I alpha 1, α-smooth muscle actin, integrins and focal adhesion kinase (FAK) were compared. More CFU-F and increased expression of C-X-C-motif-chemokine 12 were found in MC1 BMSCs, possibly indicating overrepresentation of a perisinusoidal BMSC population. RNA sequencing analysis showed enrichment in extracellular matrix proteins and fibrosis-related signalling genes. Increases in pro-collagen type I alpha 1 expression, cell adhesion, cell contractility and phosphorylation of FAK provided further evidence for their pro-fibrotic phenotype. Moreover, a leptin receptor high expressing (LEPRhigh) BMSC population was identified that differentiated under transforming growth factor beta 1 stimulation into myofibroblasts in MC1 but not in control BMSCs. In conclusion, pro-fibrotic changes in MC1 BMSCs and a LEPRhigh MC1 BMSC subpopulation susceptible to myofibroblast differentiation were found. Fibrosis is a hallmark of MC1 and a potential therapeutic target. A causal link between the pro-fibrotic phenotype and clinical characteristics needs to be demonstrated.

[Interrater reliability of the criteria-based assessment of criminal responsibility in paraphilic disorders]. / Interrater-Reliabilität der kriteriengeleiteten Beurteilung der Schuldfähigkeit bei paraphilen Störungen.

BACKGROUND: For the assessment of criminal responsibility in the context of sexual delinquency, the evaluation of the severity of a paraphilic disorder and the ability to be controlled are of particular importance. Established assessment criteria are insufficiently operationalized. AIM AND METHODS: The existing criteria were tested by experts of various professional groups with respect to the reliability. For this purpose, 14 experts assessed the criteria of 2 different sets of criteria based on 2 case vignettes (see electronic supplementary material). RESULTS AND CONCLUSION: The interrater reliability (IRR) with reference to the criteria of Briken and Müller was higher than the previously established criteria of Boetticher et al. The evaluation of the subjective importance of the criteria of both assessment scales showed that all criteria were rated as at least of average importance. It could thus be useful to initially include both sets of criteria for a greater transparency in the assessment process and to investigate this procedure in further studies.

High-power few-cycle near-infrared OPCPA for soft X-ray generation at 100 kHz.

We present a near-infrared optical parametric chirped-pulse amplifier (OPCPA) and soft X-ray (SXR) high-harmonic generation system. The OPCPA produces few-cycle pulses at a center wavelength of 800 nm and operates at a high repetition rate of 100 kHz. It is seeded by fully programmable amplitude and phase controlled ultra-broadband pulses from a Ti:sapphire oscillator. The output from the OPCPA system was compressed to near-transform-limited 9.3-fs pulses. Fully characterized pulse compression was recorded for an average power of 22.5 W, demonstrating pulses with a peak power greater than 21 GW. Without full temporal characterization, high-power operation was achieved up to 35 W. We demonstrate that at such high repetition rates, spatiotemporally flattened pump pulses can be achieved through a cascaded second-harmonic generation approach with an efficiency of more than 70%. This combination provides a compelling OPCPA architecture for scaling the peak power of high-repetition-rate ultra-broadband systems in the near-infrared. The output of this 800-nm OPCPA system was used to generate SXR radiation reaching 190 eV photon energy through high-harmonic generation in helium.

[The German version of the Bath Body Perception Disturbance Scale (BBPDS-D) : Translation, cultural adaptation and linguistic validation on patients with complex regional pain syndrome]. / Die deutsche Version der Bath Body Perception Disturbance Scale (BBPDS-D) : Übersetzung, kulturelle Anpassung und linguistische Validierung an Patienten mit komplexem regionalem Schmerzsyndrom.

BACKGROUND: Besides the classical clinical manifestations, body perception disturbances are common among patients with complex regional pain syndrome (CRPS). The Bath Body Perception Disturbance Scale (BBPDS) represents a useful tool to assess these changes in CRPS patients; however, to date no validated German version is available. OBJECTIVE: The aim of this study was to translate the BBPDS into German, to perform a cross-cultural adaptation and linguistic validation in patients with acute (symptoms <3 months) and stable (symptoms ≥3 months) CRPS. MATERIAL AND METHODS: The original English version of the BBPDS was translated into German according to published guidelines (translation and back translation) and tested on 56 patients (mean age 50.9 ± 13.1 years) with acute (n = 28) or stable (n = 28) CRPS. RESULTS: The relative reliability, intraclass correlation and test-retest reliability were excellent overall and in the groups with acute and stable CRPS. The smallest detectable change was at 10 points. In the test-retest 48 points lay within the 95% confidence interval and visual inspection showed no tendency towards heteroscedasticity. Spearman's ρ­coefficient values showed no correlation between the total score of the BBPDS-D with the numerical rating scale (NRS, ρ = -0.19) and the EuroQol-5 D (ρ = 0.16). There were no significant differences between patients with acute and stable CRPS (p = 0.412). There were also no floor or ceiling effects. CONCLUSION: This German translation and cross-cultural adaptation of the original English version of the BBPDS is a valid instrument to assess body perception disturbances in German speaking CRPS patients. Future research should further assess the impact of body perception disturbance on treatment outcome and prognosis.

THRIVE score predicts clinical and radiological outcome after endovascular therapy or thrombolysis in patients with anterior circulation stroke in everyday clinical practice.

BACKGROUND AND PURPOSE: Based on the data of several trials the Totaled Health Risks in Vascular Events (THRIVE) score has been shown to predict outcome after either intravenous thrombolysis (IVT) or endovascular therapy (ET) in acute stroke patients. It is unknown whether the THRIVE score can also predict outcome in everyday clinical practice. Using our prospectively obtained stroke database the utility of the THRIVE score to predict clinical and radiological outcome in everyday clinical practice was analysed. METHODS: The relationships between THRIVE and good outcome (modified Rankin Scale ≤ 2 at discharge), poor outcome (modified Rankin Scale 5-6), in-hospital death, symptomatic intracranial haemorrhage (SICH) as well as infarct size were examined in patients with distal intracranial carotid artery, M1 and M2 occlusions after either IVT or ET. RESULTS: From January 2008 to October 2016 a total of 546 patients were treated with IVT and 492 patients received ET with stent retrievers (with or without IVT). In both treatment groups the THRIVE score predicted clinical outcome (Mantel-Haenszel chi-squared tests for trend P < 0.001 for good outcome, P < 0.001 for poor outcome and P < 0.001 for in-hospital death). In the ET group the THRIVE score remained an independent predictor of outcome after controlling for recanalization. The THRIVE score was associated with the infarct size after IVT or ET, whereas it did not predict SICH rates in either treatment group. CONCLUSIONS: In everyday clinical practice the THRIVE score strongly predicts clinical outcome and the extent of ischaemia after ET or IVT in patients with anterior circulation large vessel occlusions.

Cost-effectiveness of conservative versus surgical treatment strategies of lumbar spinal stenosis in the Swiss setting: analysis of the prospective multicenter Lumbar Stenosis Outcome Study (LSOS).

PURPOSE: To evaluate the cost-effectiveness of conservative versus surgical treatment strategies for lumbar spinal stenosis (LSS). METHODS: Patients prospectively enrolled in the multicenter Lumbar Stenosis Outcome Study (LSOS) with a minimum follow-up of 12 months were included. Quality adjusted life years (QALY) were calculated based on EQ-5D data. Cost data were retrieved retrospectively. Cost-effectiveness was calculated via decision tree analysis. RESULTS: A total of 434 patients were included, treated surgically (n = 170) or conservatively (n = 264) for LSS. The majority of surgically treated patients underwent decompression (n = 141, 82.9%), and 17.1% (n = 29) additionally underwent fusion. A reoperation was required in 13 (7.6%) surgically treated patients. In 27 (10.2%) conservatively treated patients, a single infiltration was successful, with no further infiltration or surgery within the follow-up. However, 46 patients (17.4%) required multiple infiltrations, and in 191 (72.4%) initially conservatively treated patients a subsequent surgery was needed. The area under the curve was 0.776 QALY in the surgical arm (0.776 and 0.790, decompression or additional fusion, respectively), compared to 0.778 in the conservative arm. Treatment costs were estimated at CHF 12,958 and 13,637 (USD 13,465 and 14,169) in surgically and initially conservatively treated patients, respectively [base-case incremental cost-effectiveness ratio (ICER): CHF 392,145, USD 407,831], per QALY gained. Probabilistic sensitivity analysis identified surgery as the preferred strategy in 67.1%. CONCLUSIONS: Both the surgical and the conservative treatment approach resulted in a comparable health-related quality of life within the first year after study inclusion. Due to slightly higher costs, mostly because the majority of initially conservatively treated patients underwent multiple infiltrations or a subsequent surgery, decompressive surgery was identified as the most cost-effective approach for LSS in this setting.

[Complex regional pain syndrome]. / Komplexes regionales Schmerzsyndrom.

The term complex regional pain syndrome (CRPS) describes a variety of painful conditions, which typically occur distally on an extremity following an initiating event. Characteristically CRPS exceeds the expected clinical course in both magnitude and duration. Clinical manifestations of CRPS include sensory, vasomotor, sudomotor, motor and trophic disorders. The diagnosis of CRPS is purely clinical and based on the modified Budapest criteria. Essential differential diagnoses in the early phase include infections, neurological compression and inflammatory conditions. Although benign courses have been reported, many patients develop a chronic condition with persisting complaints even after 1 year. Therapy is based on a variety of pharmacological, interventional, physiotherapeutic, occupational and psychiatric treatment options.

[Diseases and overuse injuries of the lower extremities in long distance runners]. / Erkrankungen und Überlastungsschäden an der unteren Extremität bei Langstreckenläufern.

Running is one of the most popular sports worldwide, with running events attracting hundreds of thousands of runners of all age groups. Running is an effective way to improve health but is also associated with a high risk of injuries. Up to 50% of regular runners report having more than one injury each year. Some injuries are caused by an accident but most are caused by overuse. The most frequent diagnoses are patellofemoral pain syndrome, tibial stress syndrome (shin splint), Achilles tendinopathy, iliotibial band friction syndrome (runner's knee), plantar fasciitis and stress fractures of the metatarsals and tibia. The knee is the most frequently injured joint in runners at all distances. Hamstring injuries are typically acute resulting in a sudden, sharp pain in the posterior thigh. Hip injuries are less common but it can be more difficult to make the correct diagnosis and treatment is more complex. Clinicians confronted by runners with shin pain must distinguish between stress fractures of the tibia, tibial stress syndrome (shin splints) and chronic exertional compartment syndrome. Foot and ankle injuries are the most common injuries reported by long distance and marathon runners. Excess body weight and the number of kilometers run per week are high risk factors for injuries. The roles of other factors, such as shoes, stretching and biomechanics are less clear. A detailed anamnesis and physical examination are important for the correct diagnosis or the necessity for further diagnostic imaging and subsequent therapy.

Impact of ASPECTS on computed tomography angiography source images on outcome after thrombolysis or endovascular therapy in large vessel occlusions.

BACKGROUND AND PURPOSE: Endovascular therapy (ET) is superior to intravenous thrombolysis (IVT) in selected patients with anterior circulation large vessel occlusions. However, it is unclear if this positive effect also applies to patients with extensive early ischaemic changes. The aim of this study was to analyze the impact of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on the CT angiography source images (SI) on outcome after ET or IVT. METHODS: Using our prospectively obtained stroke database and the admission SI-ASPECTS divided into three groups (0-5, 6-7 and 8-10), primarily the rates of good outcome [modified Rankin Scale (mRS) ≤2 at discharge] after either ET (n = 255) or IVT (n = 479) were compared. RESULTS: A favorable SI-ASPECTS (8-10) was present in 501 patients, 132 patients had a moderately favorable SI-ASPECTS (6-7) and 101 patients had an unfavorable SI-ASPECTS (0-5). Irrespective of the treatment modality, no patient with an unfavorable SI-ASPECTS had a good outcome and 38% died during hospital stay. Whilst significantly more patients with a favorable SI-ASPECTS had a good outcome after ET than after IVT (51% vs. 35%, P < 0.01), there was only a non-significant trend towards a good outcome after ET than after IVT in patients with a moderately favorable ASPECTS (25% vs. 14%, P = 0.1). CONCLUSION: Patients with extensive early ischaemic changes on CT scans (SI- ASPECTS ≤5) might not profit from ET. The impact of ET on outcome in patients with moderately favorable SI-ASPECTS should be addressed in further trials.

[Case report of granulomatous necrotizing sialadenitis. Rarity of first manifestation in submandibular gland]. / Fallbericht einer granulomatös-nekrotisierenden Sialadenitis. Rarität einer Erstmanifestation in der Glandula submandibularis.

This article presents the case of a 43-year-old male patient with recurrent painful swelling of the right submandibular gland. Submandibulectomy was performed. Histological investigations showed an intense granulomatous inflammation with severe destruction of the parenchyma. The inflammatory infiltrate consisted of abscesses with neutrophilic and eosinophilic granulocytes and ill-defined granulomas with multinucleated giant cells. Some of the blood vessels showed evidence of vasculitis. After further clinical and serological investigations with highly elevated levels of cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) and antiproteinase-3 antibodies, a rare limited disease of granulomatous polyangiitis (Wegener granulomatosis) was finally diagnosed. Such a manifestation of the disease is exceedingly rare; therefore, only single case reports have so far been described. The certain establishment of the diagnosis seems to be challenging because of the lack of involvement of the respiratory tract and the kidneys. In this case a histological assessment and clinical findings are mandatory for the correct diagnosis.

Low back pain patients with Modic type 1 changes exhibit distinct bacterial and non-bacterial subtypes.

Objectives: Modic type 1 changes (MC1) are vertebral endplate bone marrow (BM) lesions observed on magnetic resonance images in sub-populations of chronic low back pain (CLBP) patients. The etiopathogenesis remains unknown and treatments that modify the underlying pathomechanisms do not exist. We hypothesized that two biological MC1 subtypes exist: a bacterial and a non-bacterial. This would have important implications for developing treatments targeting the underlying pathomechanisms. Methods: Intervertebral disc (IVD) samples adjacent to MC1 (n â€‹= â€‹34) and control (n â€‹= â€‹11) vertebrae were collected from patients undergoing spinal fusion. Cutibacterium acnes (C.acnes) genome copy numbers (GCNs) were quantified in IVD tissues with 16S qPCR, transcriptomic signatures and cytokine profiles were determined in MC1 and control BM by RNA sequencing and immunoassay. Finally, we assessed if C.acnes GCNs are associated with blood plasma cytokines. Results: IVD tissues from control levels had <870 â€‹C.acnes GCNs/gram IVD. MC1-adjacent IVDs had either "low" (<870) or "high" (>870) C.acnes GCNs. MC1 patients with "high" C.acnes GCNs had upregulated innate immune cell signatures (neutrophil, macrophage/monocyte) and pro-inflammatory cytokines related to neutrophil and macrophage/monocyte function in the BM, consistent with a host defense against bacterium. MC1 patients with "low" C.acnes GCNs had increased adaptive immune cell signatures (T-and B-cell) in the BM and elevated IL-13 blood plasma levels. Conclusion: Our study provides the first evidence for the existence of bacterial (C.acnes "high") and non-bacterial (C.acnes "low") subtypes in MC1 patients with CLBP. This supports the need for different treatment strategies.

Real-world analysis of teclistamab in 123 RRMM patients from Germany.

Teclistamab, a B-cell maturation antigen (BCMA) × CD3 directed bispecific antibody, has shown high response rates and durable remissions in the MAJESTEC-1 trial in patients with relapsed and refractory multiple myeloma (RRMM). We retrospectively assessed efficacy and tolerability in 123 patients treated at 18 different German centers to determine whether outcome is comparable in the real-world setting. Most patients had triple-class (93%) or penta-drug (60%) refractory disease, 37% of patients had received BCMA-directed pretreatment including idecabtagene vicleucel (ide-cel) CAR-T cell therapy (21/123, 17.1%). With a follow-up of 5.5 months, we observed an overall response rate (ORR) of 59.3% and a median progression-free survival (PFS) of 8.7 months. In subgroup analyses, we found significantly lower ORR and median PFS in patients with extramedullary disease (37%/2.1 months), and/or an ISS of 3 (37%/1.3 months), and ide-cel pretreated patients (33%/1.8 months). Nonetheless, the duration of response in ide-cel pretreated patients was comparable to that of anti-BCMA naive patients. Infections and grade ≥3 cytopenias were the most frequent adverse events. In summary, we found that teclistamab exhibited a comparable efficacy and safety profile in the real-world setting as in the pivotal trial.

[Sexual orientations]. / Sexuelle Orientierungen.

In this paper we study the concept of sexual orientation and its components by comparing the common orientations of hetero-, homo-, and bisexuality with alternative concepts suitable for describing persons with psychosexual and somatosexual divergencies (e.g., transgender or intersex developments). An assessment of these divergencies as well as their prevalence and societal influences are presented. Empirical findings on the relationship between sexual orientation and mental health are examined against the background of the sexual minority stress model, looking especially at the risks and the opportunities associated with belonging to a sexual minority. The paper also focuses on the normative power of a monosexual model. Finally, sexual orientation is conceptualized as an umbrella term encompassing both conscious and unconscious elements, including the aspects of sexual behavior, sexual identity, fantasies, and attraction.

Validity of outcome measures used in randomized clinical trials and observational studies in degenerative lumbar spinal stenosis.

It is unclear whether outcome measures used in degenerative lumbar spinal stenosis (DLSS) have been validated for this condition. Cross-sectional analysis of studies for DLSS included in systematic reviews (SA) and meta-analyses (MA) indexed in the Cochrane Library. We extracted all outcome measures for pain and disability. We assessed whether the studies provided external references for the validity of the outcome measures and the quality of the validation studies. Out of 20 SA/MA, 95 primary studies used 242 outcome measures for pain and/or disability. Most commonly used were the VAS (n = 69), the Oswestry Disability Index (n = 53) and the Zurich Claudication Questionnaire (n = 22). Although validation references were provided in 45 (47.3%) primary studies, only 14 validation studies for 9 measures (disability n = 7, pain and disability combined n = 2) were specifically validated in a DLSS population. The quality of the validation studies was mainly poor. The Zurich Claudication Questionnaire was the only disease specific tool with adequate validation for assessing treatment response in DLSS. To compare results from clinical studies, outcome measures need to be validated in a disease specific population. The quality of validation studies need to be improved and the validity in studies adequately cited.

City-wide wastewater genomic surveillance through the successive emergence of SARS-CoV-2 Alpha and Delta variants.

Genomic surveillance of SARS-CoV-2 has provided a critical evidence base for public health decisions throughout the pandemic. Sequencing data from clinical cases has helped to understand disease transmission and the spread of novel variants. Genomic wastewater surveillance can offer important, complementary information by providing frequency estimates of all variants circulating in a population without sampling biases. Here we show that genomic SARS-CoV-2 wastewater surveillance can detect fine-scale differences within urban centres, specifically within the city of Liverpool, UK, during the emergence of Alpha and Delta variants between November 2020 and June 2021. Furthermore, wastewater and clinical sequencing match well in the estimated timing of new variant rises and the first detection of a new variant in a given area may occur in either clinical or wastewater samples. The study's main limitation was sample quality when infection prevalence was low in spring 2021, resulting in a lower resolution of the rise of the Delta variant compared to the rise of the Alpha variant in the previous winter. The correspondence between wastewater and clinical variant frequencies demonstrates the reliability of wastewater surveillance. However, discrepancies in the first detection of the Alpha variant between the two approaches highlight that wastewater monitoring can also capture missing information, possibly resulting from asymptomatic cases or communities less engaged with testing programmes, as found by a simultaneous surge testing effort across the city.

Hemorrhagic complications after systemic thrombolysis in acute stroke patients with abnormal baseline coagulation.

BACKGROUND AND PURPOSE: As patients with abnormal baseline coagulation were excluded from the large randomized trials, the safety of intravenous thrombolysis after ischaemic stroke in this patient population remains controversial. METHODS: We assessed the risk of symptomatic intracerebral hemorrhage (SICH) after systemic thrombolysis in patients with elevated baseline international normalized ratios (INRs) (≥1.3) or activated partial thromboplastin times (aPTT) (>37 s) using a prospectively recorded database from 2006 to 2010. An intracerebral hemorrhage leading to a deterioration of ≥4 points on the National Institutes of Health Stroke scale (NIHSS) was classified as symptomatic. RESULTS: Amongst 688 patients (mean age, 72 years; median NIHSS, 11, median onset-to-treatment time, 135 min), 36 patients (5%) had an abnormal baseline coagulation. Twenty-nine of these patients had taken oral anticoagulants leading to elevated baseline INRs (median INR: 1.5; IQR 1.4-1.9), whereas seven patients had elevated aPTTs because of heparin therapy (n = 2), a coagulation disorder (n = 2), or for unknown reasons (n = 3). The rate of SICH did not differ significantly between patients with abnormal and normal baseline coagulation (4.4% vs. 0%; P = 0.6). Moreover, the in-hospital mortality was not significantly different between both treatment groups (8.3% in patients with abnormal baseline coagulation vs. 8.7% in patients with normal baseline coagulation, P = 1.0). CONCLUSIONS: The risk of SICH following intravenous thrombolysis after ischaemic stroke does not appear to be increased in patients with abnormal baseline coagulation.

Subcutaneous injection of liquid and foamed polidocanol: extravasation is not responsible for skin necrosis during reticular and spider vein sclerotherapy.

BACKGROUND: Cutaneous necrosis is one of the most annoying complications of reticular and spider vein sclerotherapy. The precise incidence of the complication is not known, although various sources reported incidence between 0.2% and 1.2%. Among a few mechanisms proposed to explain it, extravasation of the sclerosant into the perivascular tissue has been cited as the major cause. OBJECTIVES: The aim of the experimental study in rats was to examine the potential of various concentrations and volumes of polidocanol in both liquid and foam forms to cause cutaneous necrosis after superficial subcutaneous injection. METHODS: Twenty-four female Sprague Dawley rats were injected subcutaneously different concentrations (0.5%, 1%, 2% and 3%) of polidocanol as well as different preparations of polidocanol (liquid vs. foam) and volumes (0.1-0.5 mL). The animals were sacrificed 10 days after injections and biopsy specimens were obtained. RESULTS: Cutaneous necrosis was not seen at volumes <0.5 mL regardless of the concentration or form of polidocanol injected. Foam preparation was shown to be less potent in inducing necrosis with a minimal strength being 2% in comparison with the liquid form where 1% was sufficient to produce overt cutaneous necrosis. CONCLUSIONS: This experimental study shows that extravasation of polidocal in usual circumstances of sclerotherapy of spider and reticular veins cannot be a significant cause of cutaneous necrosis rarely observed in this setting. It is particularly true for the foamed polidocanol where 1% strength seems safe if injected extravascularly in volumes up to 0.5 mL.

Imaging performance of the hybrid pixel detectors XPAD3-S.

Hybrid pixel detectors, originally developed for tracking particles in high-energy physics experiments, have recently been used in material sciences and macromolecular crystallography. Their capability to count single photons and to apply a threshold on the photon energy suggests that they could be optimal digital x-ray detectors in low energy beams such as for small animal computed tomography (CT). To investigate this issue, we have studied the imaging performance of photon counting hybrid pixel detectors based on the XPAD3-S chip. Two detectors are considered, connected either to a Si or to a CdTe sensor, the latter being of interest for its higher efficiency. Both a standard 'International Electrotechnical Commission' (IEC) mammography beam and a beam used for mouse CT results published in the literature are employed. The detector stability, linearity and noise are investigated as a function of the dose for several imaging exposures ( approximately 0.1-400 microGy). The perfect linearity of both detectors is confirmed, but an increase in internal noise for counting statistics higher than approximately 5000 photons has been found, corresponding to exposures above approximately 110 microGy and approximately 50 microGy for the Si and CdTe sensors, respectively. The noise power spectrum (NPS), the modulation transfer function (MTF) and the detective quantum efficiency (DQE) are then measured for two energy threshold configurations (5 keV and 18 keV) and three doses ( approximately 3, 30 and 300 microGy), in order to obtain a complete estimation of the detector performances. In general, the CdTe sensor shows a clear superiority with a maximal DQE(0) of approximately 1, thanks to its high efficiency ( approximately 100%). The DQE of the Si sensor is more dependent on the radiation quality, due to the energy dependence of its efficiency its maximum is approximately 0.4 with respect to the softer radiation. Finally, we compare the XPAD3-S DQE with published curves of other digital devices in a similar radiation condition. The XPAD3-S/CdTe detector appears to be the best with the highest DQE at low frequency, although some improvements are expected to reduce the increase of noise with the counts statistics and to guarantee a better stability of the detector response.