An improved protocol for bacteria identification by MALDI-TOF MS directly from positive blood cultures.

FASTinov® developed a rapid antimicrobial susceptibility test that includes the purification of a bacterial suspension directly from positive blood cultures (BC). In order to streamline laboratory workflow, the use of the bacterial suspension obtained through FASTinov® sample prep was tested for identification (ID) by matrix absorption laser deionization-time of flight mass spectrometry (MALDI-TOF MS) (Bruker) in 364 positive BC, and its accuracy assessed comparing with the MALDI-TOF MS ID of the next-day subcultured colonies. FASTinov sample prep was highly reliable for rapid ID directly from BC with proportion of agreement of 94.9% for Gram-positive and 96.3% for Gram-negative bacteria.

Same-day discharge after elective percutaneous closure of patent foramen ovale.

Percutaneous closure of the patent foramen ovale (PFO) is increasingly performed in specific patients with cryptogenic stroke or clinical evidence of a paradoxical embolism. This study was performed to determine the safety of same-day discharge (SDD) following such procedures. This is a prospective, observational study of patients undergoing elective percutaneous PFO closure in a single tertiary center in Portugal between January 2020 and July 2023. AmplatzerTM devices (St. Jude Medical, St. Paul, MN, USA) and NobblestichTM EL (HeartStitch, Inc., Fountain Valley, CA, USA) were used. After 6 months, the following events were looked at: post-procedural paroxysmal atrial fibrillation, stroke, unplanned cardiac re-hospitalization, urgent cardiac surgery, major vascular complications, pericardial effusions, device embolization, and death. We studied 122 consecutive patients (52% female, 68; 48±12 years old) who had elective percutaneous closure with success and no complications. Forty-nine (40%) had SDD. AmplatzerTM devices were used more frequently in the SDD group, while NobblestichTM EL was more common in the overnight group. During the overnight group's follow-up period, there was one non-cardiovascular death; there were no further events. SDD after elective percutaneous closure of PFO was shown to be a safe and successful patient management method, including NobblestichTM, which we describe for the first time. Our results prove the safety of this same-day discharge strategy. We hypothesize that in the near future, in selected cases, PFO closure might become an ambulatory procedure.

Imported Strongyloides stercoralis infection and diabetes mellitus and other metabolic diseases: Is there any association?

OBJECTIVES: Strongyloidiasis is a nematode infection caused by Strongyloides stercoralis. Previous studies have addressed the possibility of the parasite to establish a complex relationship with the host that could affect the risk of developing diabetes mellitus or modify its presentation. This study aims to evaluate the potential impact of strongyloidiasis in diabetes mellitus and other metabolic diseases. METHODS: Case-control observational retrospective study that included 95 S. stercoralis-infected patients and 83 non-infected individuals. Epidemiological and clinical variables were retrieved from medical records, and a statistical analysis was carried out to explore any association between strongyloidiasis and diabetes mellitus and other metabolic diseases. RESULTS: Most of the patients were men (99, 55.60%) with a mean age of 42.53 ± SD 14 years. Twelve (6.70%) patients were diabetic; 30 (16.90%) presented arterial hypertension; 28 (15.70%) had dyslipidaemia; and 10 (5.60%) had thyroid pathology. When comparing patients with strongyloidiasis and uninfected patients, no differences were found regarding diabetes mellitus or other metabolic diseases. CONCLUSIONS: The results obtained in the present study do not confirm any type of association between strongyloidiasis and diabetes mellitus or other metabolic diseases.

An integrated modelling methodology for estimating global incidence and prevalence of hereditary spastic paraplegia subtypes SPG4, SPG7, SPG11, and SPG15.

BACKGROUND: Hereditary spastic paraplegias (HSPs) are progressively debilitating neurodegenerative disorders that follow heterogenous patterns of Mendelian inheritance. Available epidemiological evidence provides limited incidence and prevalence data, especially at the genetic subtype level, preventing a realistic estimation of the true social burden of the disease. The objectives of this study were to (1) review the literature on epidemiology of HSPs; and (2) develop an epidemiological model of the prevalence of HSP, focusing on four common HSP genetic subtypes at the country and region-level. METHODS: A model was constructed estimating the incidence at birth, survival, and prevalence of four genetic subtypes of HSP based on the most appropriate published literature. The key model parameters were assessed by HSP clinical experts, who provided feedback on the validity of assumptions. A model was then finalized and validated through comparison of outputs against available evidence. The global, regional, and national prevalence and patient pool were calculated per geographic region and per genetic subtype. RESULTS: The HSP global prevalence was estimated to be 3.6 per 100,000 for all HSP forms, whilst the estimated global prevalence per genetic subtype was 0.90 (SPG4), 0.22 (SPG7), 0.34 (SPG11), and 0.13 (SPG15), respectively. This equates to an estimated 3365 (SPG4) and 872 (SPG11) symptomatic patients, respectively, in the USA. CONCLUSIONS: This is the first epidemiological model of HSP prevalence at the genetic subtype-level reported at multiple geographic levels. This study offers additional data to better capture the burden of illness due to mutations in common genes causing HSP, that can inform public health policy and healthcare service planning, especially in regions with higher estimated prevalence of HSP.

Evaluation of FASTinov Ultrarapid Flow Cytometry Antimicrobial Susceptibility Testing Directly from Positive Blood Cultures.

The FASTinov flow cytometry kit, an ultrarapid antimicrobial susceptibility test, was directly evaluated on positive blood cultures (BC) at two sites: (i) FASTinov, S.A., in Porto, Portugal, using BC spiked with well-characterized bacteria, and (ii) Ramón y Cajal University Hospital in Madrid, Spain, using positive BC from patients. Two kits were evaluated, FASTgramneg (Enterobacterales, Pseudomonas, Acinetobacter) and FASTgrampos (Staphylococcus, Enterococcus). Dedicated software for cytometric data analysis and interpretative reporting, including both CLSI and EUCAST criteria, was used. The FASTgramneg kit also provides information about the presence of resistant mechanisms, including extended-spectrum beta-lactamases (ESBLs) and carbapenemases. After 1 h of incubation at 37°C, bacteria were analyzed using a CytoFLEX cytometer (Beckman, CA). Disk diffusion was performed as the reference susceptibility method. Overall, 447 positive BC were included, 100 from hospitalized patients. Categorical agreement values for the FASTgramneg panel were 96.8% based on EUCAST criteria and 96.4% based on CLSI criteria. For the FASTgrampos panel, categorical agreement was 98.6% when using both criteria. When EUCAST criteria were used, the percentages of errors for the FASTgramneg panel were 2.1% minor errors (mE), 1.3% major errors (ME), and 0.6% very major errors (VME). When CLSI criteria were used, 2.9% mE, 0.9% ME, and 0.4% VME were found. VME were mainly observed with amoxicillin-clavulanate, cefotaxime, ceftazidime, and gentamicin. The FASTgrampos panel showed 0.3% mE, 1.4% ME, and 0.4% VME when EUCAST criteria were used (VME with respect to gentamicin and Staphylococcus) and 0.4% mE, 1.4% ME, and no VME when CLSI criteria were used. The FASTinov flow cytometry kits represent a rapid alternative for direct antimicrobial susceptibility testing from positive BC, showing time to results of <2 h, and can be used to personalize antibiotic and stewardship practices.

Acute Aortic Regurgitation Due to Endocarditis Caused by Disseminated Gonococcal Infection: A Case Report.

ABSTRACT: A 23-year-old man presented with cough and progressive shortness of breath. Echocardiogram showed a biscupid aortic valve with a large vegetation causing severe regurgitation. Blood cultures were positive for Neisseria gonorrhoeae sensitive to cefotaxime and penicillin. Despite direct antibiotherapy, the patient required cardiac surgery with aortic valve replacement.

The value of chest and skeletal staging studies in conventional chondrosarcoma.

OBJECTIVE: To determine the value of chest and skeletal staging in patients presenting with conventional chondrosarcoma (CS). MATERIALS AND METHODS: Retrospective review of patients with CS diagnosed between January 2007 and December 2019. Data collected included age, sex, skeletal location and results of chest CT and whole-body bone scintigraphy (WB-BSc) obtained at initial diagnosis. The histological tumour grade based on surgical resection or needle biopsy was classified as low-grade (LGCT), high-grade (HGCT) and dedifferentiated (DD-CS). Findings of chest CT and WB-BSc were correlated with tumour grade. RESULTS: Four hundred twenty patients were included (234 males and 186 females with mean age 54.5 years, range 9-91 years). The major long bones were involved in 205 cases, the flat bones in 166 cases, the mobile spine in 14 cases and the small bones of the hands and feet in 35 cases. Three hundred fifty tumours were central in location, 39 peripheral and 31 on the surface of the bone. There were 151 LGCTs, 196 HGCTs and 73 DD-CSs. Of patients with LGCT, 41.7% underwent chest CT and 25.2% WB-BSc. Of patients with HGCT, 95.4% underwent chest CT and 76.5% WB-BSc. Of patients with DD-CS, 98.6% underwent chest CT and 86.3% WB-BSc. Metastases were diagnosed in 2 (3.3%) chest CT studies and 0 WB-BSc in LGCT, in 8 (4.3%) chest CT studies and 0 WB-BSc in HGCT and in 21 (30%) chest CT studies and 6 (21%) WB-BSc in DD-CS. DISCUSSION: Staging chest CT and WB-BSc is of little or no value except in DD-CS.

Magnetic resonance imaging of trunk and extremity myxoid liposarcoma: diagnosis, staging, and response to treatment.

Myxoid liposarcoma (MLS) accounts for approximately 30% of all liposarcomas. The majority are intermediate-grade tumours, but the presence of >5% round cell component renders it a high-grade sarcoma with subsequent poorer outcome. MLS most commonly arises in the lower extremities, has a predilection for extra-pulmonary sites of metastatic disease, and is recognized to be radiosensitive. The purpose of the current article is to review the role of MRI in the management of MLS, including the characteristic features of the primary tumour, features which help to identify a round cell component and thus determine prognosis, the role of whole-body MRI for evaluation of extra-pulmonary metastatic disease, and the utility of MRI for assessing treatment response. The MRI differential diagnosis of MLS is also considered.

The incidence and diagnostic relevance of pathological fracture in conventional central chondrosarcoma.

OBJECTIVE: To determine the incidence and diagnostic relevance of pathological fracture in patients with conventional central chondrosarcoma (CC-CS). MATERIALS AND METHODS: Retrospective review of patients with CC-CS diagnosed between January 2007 and December 2019. Data collected included age, sex, skeletal location and the presence of pathological fracture at presentation. Histological tumour grade based on surgical resection or needle biopsy was classified as atypical cartilaginous tumour (ACT)/grade 1 CS (ACT/Gd1 CS), high-grade CS (HG-CS) and dedifferentiated CS (DD-CS). The presence of pathological fracture was correlated with age, skeletal location and tumour grade. RESULTS: Three hundred seventeen patients were included (177 males and 140 females with mean age 55.8 years, range 9-91 years). Mean age of patients without pathological fracture was 54.4 years and those with pathological fracture 62.9 years (p = 0.002). The major long bones were involved in 171 cases, the flat bones in 112 cases, the mobile spine in 7 cases and the small bones of the hands and feet in 27 cases. There were 81 ACT/Gd 1 CS, 168 HGCS and 68 DD-CS. Pathological fracture was evident at presentation in 51 (16.1%) cases, the commonest bones involved being the femur (n = 21; 41.2%), humerus (n = 10; 19.6%) and acetabulum (n = 7; 13.7%). Pathological facture occurred in 7 cases of ACT/Gd 1 CS (13.7%), 23 cases of HGCS (45.1%) and 21 cases of DD-CS (41.2%) (p = 0.001). Following multivariate analysis, both older age and histological grade were independently significant factors. CONCLUSIONS: Pathological fracture was seen in 16.1% of patients with CC-CS. Pathological fractures in the femur, humerus and acetabulum very likely indicate higher tumour grade.

The importance of MRI review following the diagnosis of atypical cartilaginous tumour using image-guided needle biopsy.

OBJECTIVE: To evaluate the role of pre-biopsy MRI for management planning in patients with atypical cartilaginous tumours (ACT) diagnosed on image-guided core needle biopsy (IGCNB). MATERIALS AND METHODS: Retrospective review of patients diagnosed with ACT of the appendicular skeleton based on IGCNB who subsequently underwent surgical curettage or resection. Data collected included age, sex, skeletal location and surgical histology classified as ACT, high-grade chondrosarcoma (HG-CS) and dedifferentiated chondrosarcoma (DD-CS). Pre-biopsy MRI studies were reviewed independently by 2 radiologists blinded to surgical histology results and graded as ACT, HG-CS and DD-CS based on MRI features. RESULTS: The study included 24 males and 28 females (mean age 42.1 years; range 9-76 years). One patient had 2 lesions treated, making a total of 53 lesions. Tumours were located in the femur in 21 cases, humerus in 17, tibia in 9, radius in 4 and ulna and fibula in 1 each. Surgical histology was ACT in 41 cases, HG-CS in 10 and DD-CS in 2, indicating mismatch between IGCNB and surgical histology in 12/53 cases (22.6%). Predicted MRI grade for the 2 readers was ACT in 39 cases each, HG-CS in 13 and 14 cases and DD-CS in 1 and 0 cases. Sensitivity, specificity and accuracy of MRI for predicting HG-CS/DD-CS were 91%, 93% and 92%, respectively. Inter-observer correlation was very good (kappa = 0.94). DISCUSSION: Review of MRI findings in patients with ACT diagnosed on IGCNB is vital for identifying patients with a HG-CS/DD-CS and is recommended when planning surgical management or considering repeat IGCNB.

Zebrafish Model as a Screen to Prevent Cyst Inflation in Autosomal Dominant Polycystic Kidney Disease.

In autosomal dominant polycystic kidney disease (ADPKD), kidney cyst growth requires the recruitment of CFTR (cystic fibrosis transmembrane conductance regulator), the chloride channel that is defective in cystic fibrosis. We have been studying cyst inflation using the zebrafish Kupffer's vesicle (KV) as model system because we previously demonstrated that knocking down polycystin 2 (PC2) induced a CFTR-mediated enlargement of the organ. We have now quantified the PC2 knockdown by showing that it causes a 73% reduction in the number of KV cilia expressing PC2. According to the literature, this is an essential event in kidney cystogenesis in ADPKD mice. Additionally, we demonstrated that the PC2 knockdown leads to a significant accumulation of CFTR-GFP at the apical region of the KV cells. Furthermore, we determined that KV enlargement is rescued by the injection of Xenopus pkd2 mRNA and by 100 µM tolvaptan treatment, the unique and approved pharmacologic approach for ADPKD management. We expected vasopressin V2 receptor antagonist to lower the cAMP levels of KV-lining cells and, thus, to inactivate CFTR. These findings further support the use of the KV as an in vivo model for screening compounds that may prevent cyst enlargement in this ciliopathy, through CFTR inhibition.

Hantavirus Pulmonary Syndrome in Traveler Returning from Nepal to Spain.

Most human hantavirus infections occur in Asia, but some cases have been described in Europe in travelers returning from Asia. We describe a case of hantavirus pulmonary syndrome in a previously healthy traveler occurring shortly after he returned to Spain from Nepal. Serologic tests suggested a Puumala virus-like infection.

Imported Arbovirus Infections in Spain, 2009-2018.

To determine the epidemiologic and clinical characteristics of patients in Spain with imported arbovirus infections, we analyzed 22,655 records from a collaborative network for January 2009-December 2018. Among 861 arbovirus infections, 845 were monoinfections (456 [53%] dengue, 280 [32.5%] chikungunya, 109 [12.7%] Zika) and 16 (1.8%) were co-infections. Most patients were travelers (56.3%) or immigrants returning to Spain after visiting friends or relatives (31.3%). Median patient age was 37 years; most (62.3%) were women and some (28.6%) had received pretravel advice. Only 12 patients were immunosuppressed. Six cases (all dengue monoinfections, none in immunosuppressed patients) were severe. Since 2014, nondengue arbovirus infections increased; until 2016, chikungunya and Zika were most common. Imported arbovirus infections (mostly dengue) were frequently diagnosed, although increased chikungunya and Zika virus infections coincided with their introduction and spread in the Americas. A large proportion of cases occurred in women of childbearing age, some despite receipt of pretravel advice.

Strongyloidiasis screening in migrants living in Spain: systematic review and meta-analysis.

OBJECTIVES: To provide information regarding the prevalence of strongyloidiasis among migrants coming from Strongyloides stercoralis-endemic areas who reside in Spain. METHODS: Systematic review of the literature and meta-analysis of studies showing prevalence of S. stercoralis infection among migrants from Latin America, Africa, Eastern Europe, Asia and Oceania who reside in Spain. We included articles published until 30 April 2019 without language restriction. The keywords used for the search included 'Strongyloides stercoralis', 'strongyloidiasis', 'Spain', 'screening' and 'migrants'. RESULTS: Twenty-four studies were included in the review and meta-analysis, comprising 12 386 screened people. Eleven studies (7020 patients) evaluated the presence of S. stercoralis infection only through investigation of larvae in faeces, showing an overall prevalence of 1% (95%CI 1-1%). Thirteen studies (5366 patients) used a serological test, showing an overall prevalence of 14% (95%CI 11-17%). Strongyloidiasis seroprevalence was 20% (95%CI 15-24%) among migrants from sub-Saharan Africa, 14% (95%CI 10-18%) among those from Latin America and 8% (95%CI 5-11%) among migrants from North Africa. CONCLUSIONS: Migrants coming from strongyloidiasis-endemic areas living in Spain had a high S. stercoralis infection prevalence, particularly those from sub-Saharan Africa and Latin America. This population should be screened using serology as the most sensitive test for S. stercoralis infection. This could be easily implemented at primary care level.

OBJECTIFS: Fournir des informations sur la prévalence de la strongyloïdose parmi les migrants résidant en Espagne et provenant de zones endémiques pour Strongyloides stercoralis. MÉTHODES: Revue systématique de la littérature et méta-analyse des études montrant la prévalence de l'infection à S. stercoralis parmi les migrants d'Amérique latine, d'Afrique, d'Europe de l'Est, d'Asie et d'Océanie qui résident en Espagne. Nous avons inclus des articles publiés jusqu'au 30 avril e 2019 sans restriction de langue. Les mots clés utilisés pour la recherche comprenaient "Strongyloides stercoralis", "strongyloïdose", "Espagne", "dépistage" et "migrants". RÉSULTATS: Vingt-quatre études ont été incluses dans la revue et la méta-analyse, comprenant 12.386 personnes dépistées. Onze études (7.020 patients) ont évalué la présence d'une infection à S. stercoralis uniquement en examinant les larves dans les selles, montrant une prévalence globale de 1% (IC95%: 1-1%). Treize études (5.366 patients) ont utilisé un test sérologique, montrant une prévalence globale de 14% (IC95%: 11-17%). La séroprévalence de la strongyloïdose était de 20% (IC95%: 15-24%) chez les migrants d'Afrique subsaharienne, 14% (IC95%: 10-18%) chez ceux d'Amérique latine et 8% (IC95%: 5-11%) chez ceux d'Afrique du Nord. CONCLUSIONS: Les migrants en provenance de zones d'endémie pour la strongyloïdose vivant en Espagne avaient une prévalence élevée d'infection à S. stercoralis, en particulier ceux d'Afrique subsaharienne et d'Amérique latine. Cette population devrait être dépistée en utilisant la sérologie comme le test le plus sensible pour l' infection à S. stercoralis. Cela pourrait être facilement mis en œuvre au niveau des soins primaires.

Image-guided core needle biopsy for Ewing sarcoma of bone: a 10-year single-institution review.

OBJECTIVE: To evaluate the performance of image-guided core needle biopsy (IGCNB) for the diagnosis of Ewing sarcoma of bone. METHODS: All patients with a confirmed diagnosis of Ewing sarcoma who underwent IGCNB between January 2007 and December 2016 were included in this retrospective study. Analysis included mean age, skeletal distribution, imaging modality used for biopsy guidance, type of anaesthesia, needle type, number of passes, type of tissue sampled, and complications. RESULTS: The study included 139 patients (94 males and 45 females; mean age 18.7 years) who underwent 141 image-guided core needle biopsies as the primary diagnostic test. Of these, 101 were CT-guided, 38 ultrasound-guided, and 2 utilised both CT and ultrasound guidance. A total of 97.9% were diagnostic at first procedure. Of the 3 non-diagnostic cases, 2 underwent a further IGCNB and were positive, while 1 patient required an open surgical procedure. Only 1 patient (0.7%) suffered an immediate complication, and there were no recorded delayed complications. CONCLUSION: IGCNB is a safe procedure providing a positive diagnosis of Ewing sarcoma of bone in a very high percentage of cases. It should be the first-line method for establishing a diagnosis in suspected Ewing sarcoma of bone. KEY POINTS: • Image-guided core needle biopsy is a safe procedure providing a positive diagnosis of Ewing sarcoma of bone in a very high percentage of cases. • Image-guided core needle biopsy should be the first-line method for establishing a definitive diagnosis in Ewing sarcoma and should be performed at a specialist sarcoma referral centre. • When technically feasible, extra-osseous soft tissue alone can be sampled with confidence as there is no difference in diagnostic performance whether bone or an extra-osseous soft tissue component of the tumour is sampled.

Evaluation of ultra-rapid susceptibility testing of ceftolozane-tazobactam by a flow cytometry assay directly from positive blood cultures.

The urgent need for rapid antimicrobial susceptibility is broadly apparent from government reports to the lay press. Accordingly, we developed a flow-cytometry assay (FCM) for evaluating ceftolozane-tazobactam (C/T) susceptibility directly on blood cultures (BC) requiring < 2 h from flag positivity to report. The protocol was optimized with C/T-susceptible and C/T-resistant gram-negative bacilli inoculated in BC aerobic bottles (Becton-Dickinson, USA), and afterward optimized for different C/T concentrations (1/4, 2/4, 4/4, and 8/4 mg/L) for 1 h incubation (37 °C), followed by FCM and software analysis. Fluorescent membrane permeability and membrane potential dyes were comparatively used to detect early cell lesions using the CytoFLEX cytometer (Beckman-Coulter, USA). Repeatability, reproducibility, and stability of the assay up to 48 h after BC positivity were determined. Internal validation was performed in spiked BC bottles with 130 Enterobacterales and 32 Pseudomonas aeruginosa isolates from Porto University (Portugal), including 13 ATCC isolates. Additionally, 64 gram-negative bacilli recovered from positive BC at Ramon y Cajal Hospital (Madrid, Spain) were tested. Categorical agreement (CA) and analytical errors were calculated comparing FCM with broth microdilution results. Only the membrane potential dyes clearly distinguished CT-susceptible and CT-resistant isolates. Excellent repeatability, reproducibility, and inter-method concordance was observed. Overall, CA was 99.1% using EUCAST criteria with 2 major errors and 98.7% with CLSI criteria with 2 major and 1 minor errors. A new, accurate, and ultra-rapid FCM (< 2 h) for testing C/T susceptibility gave accurate results and would expand current FCM antimicrobial susceptibility assay.

Chondral tumours: discrepancy rate between needle biopsy and surgical histology.

OBJECTIVE: To determine the reliability of image-guided core needle biopsy (IGCNB) for the diagnosis and grading of chondral tumours of bone compared with surgical histology. MATERIALS AND METHODS: Retrospective review of patients with a chondral tumour of bone who underwent IGCNB and surgical resection between January 2007 and December 2017. Data collected included age, sex, skeletal location, technique used for IGCNB, IGCNB result including histological grade and comparison with surgical histology. RESULTS: A total of 237 patients were included (135 males and 102 females with mean age 53.7 years, range 9-89 years). A total of 174 IGCNBs were CT-guided, 57 ultrasound-guided and 6 fluoroscopic-guided. Two hundred thirty-six of 237 (99.6%) IGCNBs were diagnostic for a chondral tumour, although grade could not be determined in 13 (5.5%) due to necrosis. A positive correlation for tumour grade between IGCNB and surgical histology was achieved in 181 cases (76.4%). In 36 patients (15.2%), IGCNB under-graded the tumour, while in 6 (2.5%), IGCNB over-graded the tumour. Discrepancy between IGCNB and surgical histology was significantly greater for surface/peripheral lesions (p = 0.02) and lesions arising from the flat bones or spine (p = 0.002). DISCUSSION: IGCNB can achieve a diagnosis of a chondral tumour in a high proportion of cases when compared with final diagnosis from surgical resection specimens. However, correlation of tumour grade between IGCNB and resection histology is less reliable with discordance seen in almost one-quarter of cases, most commonly at non-appendicular sites. Therefore, IGCNB results should not be considered in isolation of imaging and clinical features when planning surgical management.

The incidence of skip metastases on whole bone MRI in high-grade bone sarcomas.

INTRODUCTION: Skip metastases have been described with osteosarcoma, Ewing sarcoma and rarely chondrosarcoma. The aim of this study was to determine the incidence of skip metastases on whole bone MRI in all primary high-grade sarcomas of the major long bones. MATERIALS AND METHOD: Retrospective review of patients from April 2007 to April 2019 with high-grade primary bone sarcomas of the humerus, radius, ulna, femur, tibia or fibula who had whole bone MRI at initial staging. Data collected included age, sex, tumour type, presence and location of skip metastases based on whole bone MRI and presence of distant metastases (the skeleton and lung). RESULTS: The study included 216 males and 171 females with mean age 30.6 years (range 4-92 years). Tumour types were as follows: High-grade osteosarcoma n = 202, Ewing sarcoma n = 68, high-grade chondrosarcoma n = 44, dedifferentiated chondrosarcoma n = 37, high-grade spindle cell sarcoma n = 29 and angiosarcoma n = 7. Skip lesions were identified in 63 (16.3%). However, after taking into account the presence of distant skeletal (n = 11) and pulmonary (n = 33) metastases, the overall incidence of skip metastases was 6.5%, occurring in 15 (7.5%) high-grade osteosarcomas, 3 (4.5%) Ewing sarcoma, 1 (2.8%) high-grade chondrosarcoma, 4 (10.8%) dedifferentiated chondrosarcomas, and 2 (6.9%) high-grade spindle cell sarcomas. A false positive MRI diagnosis of skip metastasis was made in 4 cases, 3 enchondromata and one focal nodular marrow hyperplasia. CONCLUSION: The current study has documented the incidence of skip metastases in common types of high-grade primary bone sarcoma. The possibility of false positive skip metastases has also been highlighted.

The horizontal calcaneofibular ligament: a sign of hindfoot valgus on ankle MRI.

OBJECTIVE: Hindfoot valgus malalignment has been assessed on coronal MRI by the measurement of the tibio-calcaneal (TC) angle and apparent moment arm (AMA). This study aimed to determine if the calcaneofibular ligament (CFL) angle could be used as a further marker of hindfoot valgus malalignment on routine non-weight-bearing ankle MRI. MATERIAL AND METHODS: One hundred ninety-five consecutive 3-T ankle MRI studies were identified from the hospital PACS system. The TC and CFL angles could be measured in 155 cases (78%), and the AMA on 153 cases. RESULTS: The study group comprised 56 males and 72 females with a mean age of 46 years (range 4-89 years). In 27 patients, both ankles had been imaged. The Pearson correlation between the TC and CFL angles was -0.43, with a corresponding p value of 0.001 indicating a strong negative correlation between the TC and CFL angles. The CFL angle was significantly lower in those with hindfoot valgus (113 ± 14) compared with those without (123° ± 15°) (p = 0.001). The optimal cut-off point of the CFL angle for hindfoot valgus was ≤119°, with a sensitivity and specificity of 66% and 63% respectively. The Pearson correlation between the CFL angle and AMA was -0.10, with a corresponding p value of 0.21 indicating a weak negative correlation that did not reach statistical significance. CONCLUSION: Hindfoot valgus as estimated by the increased TC angle on coronal non-weight-bearing ankle MRI is associated with a reduced CFL angle on sagittal MR images, but is not associated with AMA. Therefore, a horizontal orientation of the CFL on sagittal MR images may be a further useful sign of hindfoot valgus.

Multigenic truncation of the semaphorin-plexin pathway by a germline chromothriptic rearrangement associated with Moebius syndrome.

Moebius syndrome (MBS) is a congenital disorder caused by paralysis of the facial and abducens nerves. Although a number of candidate genes have been suspected, so far only mutations in PLXND1 and REV3L are confirmed to cause MBS. Here, we fine mapped the breakpoints of a complex chromosomal rearrangement (CCR) 46,XY,t(7;8;11;13) in a patient with MBS, which revealed 41 clustered breakpoints with typical hallmarks of chromothripsis. Among 12 truncated protein-coding genes, SEMA3A is known to bind to the MBS-associated PLXND1. Intriguingly, the CCR also truncated PIK3CG, which in silico interacts with REVL3 encoded by the other known MBS-gene REV3L, and with the SEMA3A/PLXND1 complex via FLT1. Additional studies of other complex rearrangements may reveal whether the multiple breakpoints in germline chromothripsis may predispose to complex multigenic disorders.