COVID-19 pneumonia imaging follow-up: when and how? A proposition from ESTI and ESR.

This document from the European Society of Thoracic Imaging (ESTI) and the European Society of Radiology (ESR) discusses the role of imaging in the long-term follow-up of COVID-19 patients, to define which patients may benefit from imaging, and what imaging modalities and protocols should be used. Insights into imaging features encountered on computed tomography (CT) scans and potential pitfalls are discussed and possible areas for future review and research are also included. KEY POINTS: • Post-COVID-19 pneumonia changes are mainly consistent with prior organizing pneumonia and are likely to disappear within 12 months of recovery from the acute infection in the majority of patients. • At present, with the longest series of follow-up examinations reported not exceeding 12 months, the development of persistent or progressive fibrosis in at least some individuals cannot yet be excluded. • Residual ground glass opacification may be associated with persisting bronchial dilatation and distortion, and might be termed "fibrotic-like changes" probably consistent with prior organizing pneumonia.

Publication rate of scientific abstracts presented at ESSR 2008 and 2009.

OBJECTIVE: During the ESSR 2011 Research Committee Meeting, the duration of intellectual property of a research proposal was discussed. A duration of 2 years from idea to publication was suggested. The purpose of this study was to evaluate how many ESSR 2008 and 2009 scientific abstracts were PubMed cited in print within 2 years of the congress. MATERIALS AND METHODS: In September of 2011, two researchers independently performed a literature search using author names and title words of all ESSR 2008 and 2009 scientific abstracts published in Skeletal Radiology. In case of similarity or doubt, a senior reviewer made the final decision. Publication details were recorded and analyses were performed in Microsoft Excel (Microsoft, Redmond, WA, USA). RESULTS: Until September of 2011, 62 out of 137 ESSR 2008 and 2009 scientific abstracts (45%) were PubMed cited in print [2008: 34/73 (47%); 2009: 28/64 (44%)]. 54 out of 137 abstracts (39%) were PubMed cited in print within 2 years of the congress [2008: 30/73(41%); 2009: 23/64 (36%)] including eight out of 137 abstracts (6%), which were already published before the congress [2008: 4/73 (5%); 2009: 4/64 (6%)]. The top-ranking journal in absolute numbers of publications was Skeletal Radiology. The top publishing country was the United Kingdom. Study sample size and first author position between abstract and publication did not change in the majority. CONCLUSIONS: Thirty-nine percent of ESSR 2008 and 2009 scientific abstracts were published within 2 years of the congress including 6% that were already PubMed cited in print before the congress.

Assessment of quality of life of the patients with diabetic retinopathy using National Eye Institute Visual Functioning Questionnaire (VFQ-25).

BACKGROUND: Diabetes affects most of the organs causing macrovascular and microvascular complications. Diabetic retinopathy (DR) results from the prolonged uncontrolled hyperglycemia which causes impairment of vision. Quality of life (QoL) of patients with DR is affected due to vision loss. National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) is the questionnaire used to study the effect of DR on QoL. OBJECTIVES: To assess the QoL of the patients with DR. MATERIALS AND METHODS: The study enrolled 149 (male-104 and female 45) patients with DR. The previous translated and validated version of NEI-VFQ-25 questionnaire was used in the study. RESULTS: Cronbach alpha for internal consistency was between 0.6 and 0.8. The male patient showed significantly higher (p<0.05) QoL scores (60.73±1.63) as compared to the female patients (53.15±2.84). Hypertensive patients showed poor QoL as compared to non-hypertensive patients. The patients with a history of diabetes for 16-30 yrs. showed better QoL as compared to other patients. CONCLUSION: DR affects the QoL of life of patients. Routine assessment of QoL using NEI-VFQ-25 questionnaire would be useful for physicians and health care team.

Outcomes of femoral de-rotation osteotomy for treatment of femoroacetabular impingement in adults with decreased femoral anteversion.

Decreased femoral anteversion is an often overlooked factor in femoroacetabular impingement (FAI), with potential to exacerbate both cam and pincer type impingement, or itself be the primary cause. Femoral de-rotation osteotomy (FDO) is a surgical option for symptomatic patients with such underlying bony deformity. This study aimed to investigate outcomes of FDO for management of symptomatic FAI in the presence of decreased (<5°) femoral anteversion. Secondary aims were to describe the surgical technique and assess complications. This study included 33 cases (29 patients) with average pre-operative anteversion measuring -3.1° (true retroversion). At an average follow-up of 1.5 years (19.8 months), 97% reported significant improvement. The overall average post-operative International Hip Outcome Tool (iHOT-33) score of 70.6 points (r: 23-98) compared to the average pre-operative score of 42.8 points (r: 0-56) for the 11 patients with available pre-operative scores suggests an overall improvement. The minimal clinically important difference for the iHOT-33 is 6.1 points. Patients with both pre- and post-operative iHOT-33 scores available demonstrated a statistically and clinically significant improvement of 37.7 (r: 13-70) points. There were three cases (9%) of delayed union and two cases (6%) of non-union early in the series which prompted evolution of the technique. Locking screw removal was performed in 33% of patients for a resultant overall re-operation rate of 45%. The findings suggest improvement in patient-reported outcomes can be achieved with FDO for symptomatic FAI in the setting of decreased femoral anteversion (<5°).

Antenatal ultrasound and postnatal autopsy findings in terminations after 12 weeks' gestation due to fetal abnormality: population-based study in Western Norway, 1988-2002.

BACKGROUND: Ultrasound screening has been part of antenatal care for several decades, and warrants high expertise to meet the criteria for a worthwhile screening program. In particular, the rate of false positives should be low. PURPOSE: To examine time trends of pregnancy terminations for fetal abnormality after 12 weeks' gestation, and to assess the agreement between antenatal ultrasound and post-termination autopsy findings for the main pathologies leading to termination. MATERIAL AND METHODS: During the period 1988 to 2002, 198 pregnancies were terminated for fetal abnormality after 12 weeks' gestation. We reviewed the case notes for those 151 who were autopsied (male/female/undetermined ;= ;91/56/4). Annual rates of live births and stillbirths were retrieved from the Medical Birth Registry of Norway. RESULTS: Antenatal ultrasound provided a correct diagnosis of the major abnormality in 149/151 cases (99%), based on post-termination autopsy findings. The annual rate of terminations after 12 weeks' gestation varied between 0.6 and 3.4 (mean 1.8) per 1000 live births, with a trend toward higher rates over the study period (P=0.001, chi-square test for linear-by-linear association). CONCLUSION: The specificity of antenatal ultrasound for major abnormalities was high, as compared to postnatal autopsy findings. The mean annual rates of termination after 12 weeks' gestation tended to increase over the 14-year study period.

Overlapping sites on the Link module of human TSG-6 mediate binding to hyaluronan and chrondroitin-4-sulphate.

Link modules are hyaluronan-binding domains that are involved in the formation and stability of extracellular matrix and cell migration. We have examined the glycosaminoglycan specificity of the Link module from the arthritis-associated protein, human TSG-6, by microtitre plate-based assays employing biotinylated-hyaluronan or mono-biotinylated Link module. This domain was found to interact specifically with chondroitin-4-sulphate (C4S), with similar affinity to hyaluronan, but not with chondroitin-6-sulphate or heparin. Competition experiments indicate that C4S and hyaluronan have overlapping binding surfaces on the TSG-6 Link module. Disease-associated changes in C4S expression may influence the localisation and biological role of TSG-6.

TSG-6 interacts with hyaluronan and aggrecan in a pH-dependent manner via a common functional element: implications for its regulation in inflamed cartilage.

Cartilage matrix is stabilised by the interactions of proteins with hyaluronan (HA). We compare the pH dependences of HA binding by aggrecan, link protein and TSG-6. Aggrecan and link protein exhibit maximal binding across a wide pH range (6.0-8.0). TSG-6, a protein that is only produced during inflammation, binds maximally at about pH 6.0 but shows a dramatic loss of function with increasing pH. TSG-6 also interacts with aggrecan, with a similar pH dependence, and this can be inhibited by HA. Thus, a common binding surface on TSG-6 may be involved in HA and aggrecan binding. We propose that TSG-6 is involved in matrix dissociation and that this is regulated by pH gradients in cartilage.

Analysis of cellular adhesion by microarray expression profiling.

Microarrays of oligonucleotides or cDNAs can be used to establish the expression profiles of numerous genes in a single experiment. We have established a microarray platform to identify genes in a number of different pathological conditions, particularly those with an inflammation component. This platform utilised the output of an eosinophil sequencing project in which 1069 sequences were identified that were not represented in the public domain. An eosinophil model cell line, AML14.3D10, was used to investigate cell adhesion. The transcription profile of adhered and non-adhered AML 14.3D10 cells was shown to be both technically and biologically reproducible. A number of genes were found differentially expressed in the adhered vs. non-adhered populations. In the adhered population, the expression of these genes was restricted compared to brain, lung, kidney and especially bone marrow. However, the differentially regulated genes were not among those genes most restricted to eosinophils. We discuss the implications of transcription profiling on gene annotation and its potential utility for the identification of targets for drug intervention.

Clinical implications of urokinase and tissue type plasminogen activators and their inhibitor (PAI-1) in breast cancer tissue.

Cytosol of primary breast cancers from 217 women of predominantly Arab ethnicity were assayed for uPA, tPA, PAI-1 and a subset for ER, PR and pS2. Serum levels of CEA and CA153 were determined during follow-up. Only tPA correlated to nodal status and tumour grade, and PAI-1 to clinical stage. PAI-1 was related to uPA and both were inversely correlated with PR and pS2 (PAI-1 also to ER). Conversely tPA was directly correlated with ER, PR and pS2. Women with high tumour uPA and PAI-1, but not tPA, had shorter overall, and relapse-free, survival. Only nodal status and clinical stage were independent predictors in multivariate analysis. However, uPA and PAI-1 were more prognostically informative than ER or PR and their usefulness may extend to delineation of patients likely to respond to adjuvant therapy.

Distal radius triplane fracture.

A triplane fracture is so named because of the three planes traversed by the fracture line. These are physeal fractures that result from injury during the final phase of maturation and cessation of growth. This fracture pattern typically involves the distal tibia. We present a rare case of a triplane fracture involving the distal radius.

Bilateral mucoid degeneration of the posterior cruciate ligaments.

Mucoid (myxoid) degeneration of the anterior cruciate ligament (ACL) is well documented and well known. Mucoid degeneration of the posterior cruciate ligament (PCL) has been reported, but is rare in comparison. The changes may be subtle and may be missed if one is not aware of the diagnosis. As in the ACL, degeneration may cause pain and discomfort. Recognition of the pathology and correct diagnosis is important for the patient and referring physician, as this may have an impact on the therapeutic strategy. We present a case of mucoid degeneration of both PCLs, which to the best of our knowledge has not been published before in the medical literature, as a probable cause of knee pain due to habitual kneeling.

Regeneration of tendo Achillis.

A child with traumatic laceration of the tendo Achillis developed secondary infection after primary repair. This resulted in the loss of 5 cm of the distal part of the tendon and overlying soft tissue. The patient was treated with a free skin flap to cover the wound and to control the infection leaving reconstruction for a second-stage procedure. However, when he was assessed two years after the skin-flap, delayed reconstruction proved to be unnecessary since he had regained normal ankle function spontaneously and could demonstrate equal function in both tendons.

Steroid receptor measurement in breast cancers: comparison between ligand binding and enzyme-immunoassay in cytosolic and nuclear extracts.

We have analysed cytoplasmic and nuclear extracts of breast-cancer tissue from a total of 799 patients, measuring both oestrogen and progesterone receptors (ER, PR) using either the ligand binding assay (LBA) or the enzyme immunoassay technique (EIA). Mean and median receptor levels were much lower than those widely reported by others. For ER, this may in part be a consequence of the younger median age of the patient group. The frequency of positivity, using consensus cut-off values for clinical evaluation, was also lower than that reported by the EORTC Receptor Study Group. Although the measurements comparing the 2 methods were statistically correlated in terms of positivity, based on the above criteria for clinical assessment, concordance was considered to be relatively poor, particularly for ER when assayed in the same samples by the 2 methods. In cytosolic but not nuclear extracts, the LBA method gave a higher median value for ER than the EIA (except in the group that had EIA values greater than 15 fmol/mg protein); for PR, median values were higher with EIA in both cell fractions. There was an excellent correlation between receptor amounts in cytosolic and nuclear extracts for both ER and PR using the EIA; this was significantly better than with LBA. We also observed a correlation between ER and PR in both cytosolic and nuclear fractions which was most pronounced when the analysis was done by EIA. The amounts of ER in the cytosolic fraction were also correlated with the those of PR in the nuclear fraction and ER in the nuclear fraction with PR in the cytosolic fraction, but only when the EIA method was used. We conclude that the EIA method appears to be more sensitive and gives biologically more reliable results. However, the disagreement between the methods may be due to legitimate recognition of altered forms of the receptor and may be of biological significance. Although the presence of receptor in the cytosolic fraction is artifactual, its measurement by EIA does parallel the amounts of nuclear receptor, which may be a more relevant biological parameter.

Immunoradiometric measurement of pS2 in breast cancer--correlation with steroid receptors and plasminogen activators.

pS2 was measured by radioimmunometric assay in tumour extracts from 197 breast cancer patients. Values ranged from 0 to 50 ng/mg protein (mean 9.6 and median 3 ng/mg). We found no correlation with age, menopausal status, nodal metastases, disease stage or tumour histology. There was, however, a linear relationship with both ER (p < 0.0001) (particularly nuclear ER) and PR (p < 0.0001) expression determined by enzyme immunoassay (ELISA), as well as a good correlation when high and low expressors were stratified on the basis of combined ER/PR expression using consensus cut-off points. Only 15% of ER - ve/PR - ve patients were classified as pS2 + ve compared with 83% of those who were ER + ve/PR + ve. pS2 was also directly correlated with high expression of tPA and inversely with uPA. Comparison with previous studies showed that the current ELISA method produced consistent results, in contrast to other methods, particularly those based on immunohistochemical detection. The close relationship between pS2 and both steroid receptors suggests that pS2 may be important in terms of defining hormone-responsive patients who are likely to benefit from endocrine therapy.

Measurement of serum N-acetyl beta glucosaminidase activity in patients with breast cancer.

N-acetyl-beta-glucosaminidase (NAG) activity measured in sera from 129 breast cancer patients was elevated (mean 18.2 units/l) compared with that in sera from 28 healthy women (11.6 units/l) (p=0.001). There was a weak correlation between NAG activity and carcinoembryonic antigen (CEA) and CA-153, but no relationship to age, menopausal status, node status, stage, histology of tumour or to steroid receptors. NAG, CEA and CA-153 were measured in periodic follow-up samples taken after surgery (up to 26 months) from 17 patients. NAG activity fluctuated within a narrow range, unlike CEA and CA-153. In 70% of cases the pattern was similar to at least one of the other markers, and was generally maintained at a higher level in patients who suffered relapse compared with those who remained disease-free up to the last follow-up, but was not significantly altered before relapse. The measurement of NAG activity is unlikely to be of value in predicting time or occurrence of relapse or of clinical utility in post-surgical therapy. Increased appearance in serum may aid metastasis by degrading the extracellular matrix and it may be better investigated as a predictor of progression from in situ to invasive and metastatic cancer.

Large-scale expression, refolding, and purification of the catalytic domain of human macrophage metalloelastase (MMP-12) in Escherichia coli.

We have cloned, overexpressed, and purified the catalytic domain (residues Gly106 to Asn268) of human macrophage metalloelastase (MMP-12) in Escherichia coli. This construct represents a truncated form of the enzyme, lacking the N-terminal propeptide domain and the C-terminal hemopexin-like domain. The overexpressed protein was localized exclusively to insoluble inclusion bodies, in which it was present as both an intact form and an N-terminally truncated form. Inclusion bodies were solubilized in an 8 M guanidine-HCl buffer and purified by gel filtration chromatography under denaturing conditions. Partial refolding of the protein by dialysis into a 3 M urea buffer caused selective degradation of the truncated form of the protein, while the intact catalytic domain was unaffected by proteolysis. An SP-Sepharose chromatography step purified the protein to homogeneity and served also to complete the refolding. The purified protein was homogeneous by mass spectrometry and had an activity similar to that of the recombinant enzyme purified from mammalian cells. The protein was both soluble and monodisperse at a concentration of 9 mg/ml. This purification procedure enables the production of 23 mg of protein per liter of E. coli culture and is amenable to large-scale protein production for structural studies.

Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration.

Link modules are hyaluronan-binding domains found in proteins involved in the assembly of extracellular matrix, cell adhesion, and migration. The solution structure of the Link module from human TSG-6 was determined and found to consist of two alpha helices and two antiparallel beta sheets arranged around a large hydrophobic core. This defines the consensus fold for the Link module superfamily, which includes CD44, cartilage link protein, and aggrecan. The TSG-6 Link module was shown to interact with hyaluronan, and a putative binding surface was identified on the structure. A structural database search revealed close similarity between the Link module and the C-type lectin domain, with the predicted hyaluronan-binding site at an analogous position to the carbohydrate-binding pocket in E-selectin.