MRI of brachial plexus using diffusion tensor imaging: a pilot study for the use of resolve sequence surgical and radiologic anatomy.

BACKGROUND: Clinical exam is the goldstandard for surgical indication. ENMG and conventional MRI are insufficient to understand the highly variable clinical presentation of brachial plexus (BP) lesions. DTI is based on motion of water molecules and can explore nerve function. PURPOSE: This pilot study of healthy subjects aimed to develop RESOLVE sequence for BP exploration using diffusion MRI. The main objective was to provide complete precise information from DTI cartography associated with anatomical data. METHODS: Six healthy volunteers were scanned using 3T PRISMA scanner with anatomic 3D STIR SPACE and RESOLVE diffusion sequences. Diffusion parametric maps of fractional anisotropy (FA) were extracted from RESOLVE acquisitions. A reproducible method for roots volumes and angles measurements was created using 3DSlicer. ROI were segmented on Mean B0 sequences. FA measurements were obtained with ROI on Mean B0 sequences. RESULTS: RESOLVE sequence was adapted to the BP. Mean FA was 0.30. Angles measurements on 3D STIR SPACE sequences showed increasing values from proximal to distal roots with an 0.6 ICC. Volume measurements on anatomic sequences varied widely from one root to another but did not show any significant difference on laterality. CONCLUSIONS: A new and reproducible method for BP exploration was developed, using MRI RESOLVE DTI sequences. Complete mapping was obtained but a low resolution of track density imaging did not allow to exploit distal nerves. Deterministic tractography principal limit was the lack of resolution. Extraction of diffusion, volumetric and angular parameters of the plexus roots, and scripts creation for image processing was adapted to the healthy BP.

[Release of amniotic constricted grooves by hemi-circumferential excision and skin closure without Z-plasty]. / Libérations des sillons de constriction amniotique par excision hémi-circonférentielle et fermeture cutanée sans plastie en Z.

INTRODUCTION: Constriction grooves are typical abnormalities of constriction band syndrome (CBS). Treatment by complete excision and Z-plastic closure is the gold standard for release of these grooves. However, the results of these Z-plasties are often judged to be aesthetically insufficient. The hypothesis was that direct excisional surgery without Z-plasty gave better aesthetic results. The objectives of this study were (1) to evaluate the clinicaal results of the release of amniotic furrows by simple hemi-circumferential excision without resorting to Z-plasties, (2) to study the occurrence of complications, (3) to study the factors leading to complications. MATERIALS AND METHODS: All patients who had release of amniotic grooves by linear hemi-circumferential excision and closure without Z-plasties were included between 2011 and 2017. Release of complete or circumferential grooves was carried out in 2 stages. Clinical evaluation was based on parental satisfaction with the aesthetic appearance and occurrence of any complications or recurrence. RESULTS: Fourteen grooves including 8 circumferential and 6 semi-circumferential were released, in 7 patients. Average age at surgery was 9 months (3-18 months). Some patients had 1, 2 or 3 surgeries. The groove was localized in 7 cases in the leg, in 4 in the fingers and in 1 in the thigh, toes and forearm. At the last average follow-up of 25 months (12-41 months), all parents were very satisfied with the aesthetic appearance. No complications, including scarring, vascular or lymphatic disease, were noted. No recurrence was noted. CONCLUSION: Release of amniotic grooves by simple linear hemi-circumferential excision without Z-plasties is a simple, safe and effective technique. The aesthetic results are very satisfactory. LEVEL OF EVIDENCE: IV - retrospective study.

Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

Meropenem-clavulanate for drug-resistant tuberculosis: a follow-up of relapse-free cases.

BACKGROUND: Extensively drug-resistant tuberculosis (XDR-TB), defined as TB caused by a Mycobacterium strain resistant to at least rifampicin, isoniazid, any fluoroquinolone and one of the injectable anti-tuberculosis drugs, remains a worldwide public health threat. Among repurposed drugs empirically used for XDR-TB cases, carbapenems have been studied in vitro and in animal models, with encouraging results. However, only short-term follow-up data from clinical studies are currently available. OBJECTIVES: To study the long-term follow-up of XDR-TB cases treated with a regimen containing meropenem-clavulanate (M/Clav). DESIGN: Retrospective observational case series study at a single hospital. METHODS: All hospitalised drug-resistant TB patients who received M/Clav as part of their treatment from 2009 to 2016 were included. Demographic and clinical data were extracted from medical records. RESULTS: Eighteen XDR-TB patients were included in the analysis. The successful outcome and mortality rates were respectively 83.3% and 11.1%. No relapses were observed in cured patients after a median follow-up of 4 years. No specific adverse events were attributed to treatment with M/Clav. CONCLUSION: The rate of sustained successful treatment outcome observed here is far higher than the 26% observed in the 2014 World Health Organization XDR-TB cohort, suggesting that carbapenems may be beneficial for the treatment of difficult-to-treat TB cases.

Team approach to manage difficult-to-treat TB cases: Experiences in Europe and beyond.

As recommended by the World Health Organization (WHO), optimal management of MDR-TB cases can be ensured by a multi-speciality consultation body known as 'TB Consilium'. This body usually includes different medical specialities, competences and perspectives (e.g., clinical expertise both for adults and children; surgical, radiological and public health expertise; psychological background and nursing experience, among others), thus lowering the risk of making mistakes - or managing the patients inappropriately, in order to improve their clinical outcomes. At present, several high MDR-TB burden countries in the different WHO regions (and beyond) have introduced TB Consilium-like bodies at the national or subnational level to reach consensus on the best treatment approach for their patients affected by TB. In addition, in countries/settings where a formal system of consultation does not exist, specialized staff from MDR-TB reference centres or international organizations usually spend a considerable amount of their working time responding to phone or e-mail clinical queries on how to manage M/XDR-TB cases. The aim of this manuscript is to describe the different experiences with the TB Consilia both at the international level (European Respiratory Society - ERS/WHO TB Consilium) and in some of the countries where this experience operates successfully in Europe and beyond. The Consilium experiences are described around the following topics: (1) history, aims and focus; (2) management and funding; (3) technical functioning and structure; (4) results achieved. In addition a comparative analysis of the TB Consilia in the different countries has been performed.

Isolation unit for multidrug-resistant tuberculosis patients in a low endemic country, a step towards the World Health Organization End TB Strategy.

Tuberculosis (TB) remains a threat to public health and is the second cause of death due to a single infectious agent after HIV/AIDS. The worldwide distribution of TB is heterogeneous. The incidence is decreasing in most high-income regions, but the situation remains worrying in many parts of the world. The emergence of Mycobacterium tuberculosis strains resistant to key agents used in treatment (rifampin and isoniazid) contributes to TB transmission around the world. To achieve TB elimination, both high and low endemic countries must upscale their efforts to decrease disease transmission and improve cure rates. Management of drug-resistant TB is of particular importance. In this paper, we discuss the different models of care of multidrug-resistant TB (MDR-TB), the ethical considerations and the specific constraints present in high income countries. The management model chosen by the Belgian TB specialists in accordance with public health authorities as well as building of a specific MDR/XDR-TB isolation unit are also discussed.

Optogenetic activation of intracellular adenosine A2A receptor signaling in the hippocampus is sufficient to trigger CREB phosphorylation and impair memory.

Human and animal studies have converged to suggest that caffeine consumption prevents memory deficits in aging and Alzheimer's disease through the antagonism of adenosine A2A receptors (A2ARs). To test if A2AR activation in the hippocampus is actually sufficient to impair memory function and to begin elucidating the intracellular pathways operated by A2AR, we have developed a chimeric rhodopsin-A2AR protein (optoA2AR), which retains the extracellular and transmembrane domains of rhodopsin (conferring light responsiveness and eliminating adenosine-binding pockets) fused to the intracellular loop of A2AR to confer specific A2AR signaling. The specificity of the optoA2AR signaling was confirmed by light-induced selective enhancement of cAMP and phospho-mitogen-activated protein kinase (p-MAPK) (but not cGMP) levels in human embryonic kidney 293 (HEK293) cells, which was abolished by a point mutation at the C terminal of A2AR. Supporting its physiological relevance, optoA2AR activation and the A2AR agonist CGS21680 produced similar activation of cAMP and p-MAPK signaling in HEK293 cells, of p-MAPK in the nucleus accumbens and of c-Fos/phosphorylated-CREB (p-CREB) in the hippocampus, and similarly enhanced long-term potentiation in the hippocampus. Remarkably, optoA2AR activation triggered a preferential p-CREB signaling in the hippocampus and impaired spatial memory performance, while optoA2AR activation in the nucleus accumbens triggered MAPK signaling and modulated locomotor activity. This shows that the recruitment of intracellular A2AR signaling in the hippocampus is sufficient to trigger memory dysfunction. Furthermore, the demonstration that the biased A2AR signaling and functions depend on intracellular A2AR loops prompts the possibility of targeting the intracellular A2AR-interacting partners to selectively control different neuropsychiatric behaviors.

Meningitis and splenic infarction due to disseminated Mycobacterium genavense infection in an HIV patient. Case report and review of the literature.

We report a case of disseminated infection with Mycobacterium genavense in a 58 year old HIV positive woman presenting with fever, diarrhea, abdominal pain and weight loss. She had a striking hepatosplenomegaly, abdominal lymphadenopathy, anaemia and thrombopenia. Direct smears and cultures of blood, stool, sputum, urine and bone marrow were negative for common and opportunistic microorganisms. Splenectomy revealed numerous acid fast bacill. Lumbar puncture also showed acid fast bacilli at direct examination. Specific PCR and 16s rRNA gene sequencing identified M. genavense. The outcome was fatal despite antimycobacterial therapy. M. genavense must be included in the differential diagnosis of fever, weight loss, lymphadenopathy and splenomegaly in immunocompromised patients. Prompt diagnosis is based on molecular biology methods. Empirical therapy, using at least three antimycobacterial agents, including clarithromycin should be introduced in case of high clinical suspicion.

Epidemiology of MDR-TB in a Belgian infectious diseases unit: a 15 years review.

INTRODUCTION: For the last 20 years the world has seen the emergence of a growing epidemic of MDR-TB, followed by the appearance of XDR-TB. Both require longer, more expensive and more toxic treatments. MDR-TB and especially XDR-TB are associated with a lower cure rate than non MDR-TB. MATERIALS AND METHODS: We reviewed retrospectively all cases of MDR-and XDR-TB managed at St Pierre University Hospital between 1996 and 2010. Epidemiological, clinical, bacteriological, treatment, follow up and outcome were collected and analysed. RESULTS: We recorded 73 instances of MDR-TB and 11 XDR-TB for a total of 78 patients. All but 4 patients were of non Belgian origin. 10 patients were co-infected with HIV. A median of 4 active drugs (1-5) were used for a median of 448 days (329-616). 41 MDR-TB (56%) and 1 XDR-TB (1%) were considered as cured and 20 are still on treatment. Since 2007, increasing resistance to second line injectable drugs, fluoroquinolones and even linezolid (1 case) is observed. Extensive resistance was mainly found in patients who had previously been mismanaged with second line agents. CONCLUSIONS: This study illustrates the growing epidemic of MDR and XDR-TB, it emphasizes the importance of proper diagnosis and adequate management of TB in patients at risk for resistance and stresses the need for new therapies.

Clinical use of the meropenem-clavulanate combination for extensively drug-resistant tuberculosis.

Mycobacterium tuberculosis strains resistant to almost all available anti-tuberculosis drugs are an increasing threat to public health worldwide. Among existing drugs with potential antimycobacterial effects, the combination of meropenem with clavulanate has been shown to have potent in vitro bactericidal activity against extensively drug-resistant tuberculosis (XDR-TB). To explore its potential clinical efficacy, a meropenem-clavulanate-containing salvage regimen was started in six patients with severe pulmonary XDR-TB, in association with the only one or two remaining active second-line drugs. Encouraging preliminary data are detailed and discussed.

Thyroid volume measured by ultrasonography and CT.

PURPOSE: To evaluate measurements of thyroid volume by two different US methods and CT in a blinded design. MATERIAL AND METHODS: Four observers evaluated 27 patients. Observer 1 used US and calculated thyroid volume based on recordings of cross-sections through the gland. Observer 2 used US and calculated the volume of each lobe as a rotation ellipsoid. Observers A and B used CT images and calculated thyroid volume based on recordings of cross-sections through the gland. All measurements were made twice. RESULTS: The median thyroid volume was 81 ml (range 7-470 ml) evaluated by CT. All three methods had fair reproducibility. When correlating the two different methods using US, an r of 0.837 was found. When correlating data from patients without intrathoracic goitre evaluated by US (Observer 1) and CT, r = 0.945. The method based on a rotation ellipsoid systematically produced smaller thyroid volumes than those of the cross-sectional method. Evaluation by US systematically produced smaller thyroid volumes than CT. CONCLUSION: Calculation of thyroid volume based on US recordings of cross-sectional areas is a reproducible method in patients without substernal goitre extension. The US method calculating thyroid volume as a rotation ellipsoid is less reproducible, especially in large goitres. Measurement of thyroid volume using CT should be preferred in goitres with substernal extension.

US-guided fine-needle aspiration biopsy of thyroid nodules.

PURPOSE: To determine which nodular areas provide most adequate and accurate material for cytology during US-guided fine-needle aspiration biopsy (FNAB) of thyroid nodules. MATERIAL AND METHODS: In a prospective multicentre study, US-guided FNAB (0.8 mm) was performed in 342 thyroid nodules (338 patients, 285 women, 18-83 years, 285 palpable). Histology was obtained in 169 nodules, revealing 75 neoplasms (44.4%) including 18 cancers (10.7%). In 206 solid nodules, 2 passes (central and peripheral) were compared. In 82 complex nodules, 2 passes (solid area and cystic area) were compared. RESULTS: The inadequacy rate was 16.4% and the false-negative rates were 2.2% and 28.1% for the diagnosis of cancer and neoplasm, respectively. In solid nodules, material was more adequate with peripheral passes compared to central passes, but the difference was not significant. In complex nodules, the inadequacy rate was much higher for passes in cystic areas (80.5%) compared to passes in solid areas (46.3%). CONCLUSION: Cystic areas due to degeneration seldom provided adequate material when aspirated. Aspiration should always be obtained from solid areas, at best using US-guidance. Adenomas and non-neoplastic nodules were difficult to distinguish.

Power Doppler ultrasonography for assessment of synovitis in the metacarpophalangeal joints of patients with rheumatoid arthritis: a comparison with dynamic magnetic resonance imaging.

OBJECTIVE: To evaluate the effectiveness of power Doppler ultrasonography (PDUS) for assessing inflammatory activity in the metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA), using dynamic magnetic resonance imaging (MRI) as a reference method. METHODS: PDUS and dynamic MRI were performed on 54 MCP joints of 15 patients with active RA and on 12 MCP joints of 3 healthy controls. PDUS was performed with a LOGIQ 500 unit by means of a 7-13-MHz linear array transducer. Later the same day, MRI was performed with a 1.0T MR unit. A series of 24 coronal T1-weighted images of the second through the fifth MCP joints was obtained, with intravenous injection of gadolinium diethylenetriaminepentaacetic acid after the fourth image (dynamic MRI). From the MR images, the rate of early synovial enhancement (RESE; defined as the relative enhancement per second during the first 55 seconds postinjection) was calculated and compared with the flow signal on PDUS, which was scored as present or absent. RESULTS: In RA patients, flow signal on PDUS was detected in 17 of 54 MCP joints examined. Postcontrast MR images revealed an RESE of > or = 1.0%/second in 18 of 54 RA MCP joints. PDUS showed no flow in 47 of 48 MCP joints with an RESE of <1.0%/second and revealed flow in 16 of 18 MCP joints with an RESE of > or = 1.0%/second. Using dynamic MRI as a reference, PDUS had a sensitivity of 88.8% and a specificity of 97.9%. CONCLUSION: PDUS was reliable for assessing inflammatory activity in the MCP joints of RA patients, using dynamic MRI as the standard. PDUS and clinical assessment of joint swelling/tenderness were only weakly correlated.

[Lipids and AIDS]. / Lipides et SIDA.

HIV infection induces an early decrease of cholesterol and a late increase of triglycerides (TG) with a reduction of HDL. These changes are proportional with the lowering of CD4, which reflects the infection's severity. Both the increase of TG synthesis and the decrease of TG catabolism, in relation with a reduction of lipoprotein lipase activity, are responsible of these changes. Moreover, LDL catabolism is enhanced by macrophage scavenger receptors, due to a high proportion of small, dense LDL which are more easily oxidized. Many cytokines (interferon alpha, interleukins, TNF) play probably a pathogenic role in the dyslipidemia. Some HIV patients who received antiproteases may develop lipodystrophy with central obesity, insulino-resistance, glucose intolerance and sometimes diabetes (like in syndrome X). Other patients present a cushingoid, buffalo hump. This complication may be observed also with antiretroviral treatment other than antiproteases. The physiopathology of these findings could be in relation with structural homologies between antiproteases and some important proteins, involved in lipid and adipocyte metabolism. Cardiovascular risk linked to these perturbations is evident. The treatment is not different from the treatment for seronegative, hyperlipidemic patients: struggle against risk factors, diet advices, fibrates or statins. The antiproteases bring huge contribution to the prognosis of AIDS patients but the risk of cardiovascular complications could impair this therapeutic progress. So, it is essential to understand the pathogeny of these complications in order to discover new antiproteases, without these adverse side effects.

Impact of intraoperative ultrasonography on surgical treatment of liver tumours.

PURPOSE: The aim of this study was to evaluate the impact of intraoperative ultrasonography (IOUS) on surgical decision-making in patients with liver tumours. MATERIAL AND METHODS: IOUS of the liver was performed in 116 patients undergoing surgery for liver tumours. The patients were evaluated preoperatively by ultrasonography, CT and in some cases, by ERCP and scintigraphy. IOUS findings were compared with the results of preoperative imaging and surgical findings. RESULTS: The surgical procedures were altered in 50 cases (43%), extended in 19 cases (16%) and reduced in 8 cases (7%). Twenty-three patients (20%) were found inoperable. Intraoperative evaluation caused surgical modification by IOUS in 13 patients (11%), by surgical findings in 14 patients (12%) and by a combination of both in 23 patients (20%). CONCLUSION: IOUS is a precise diagnostic method for staging the operability of liver tumours. Unnecessary surgical procedures can be avoided. In total, IOUS altered the preoperative plan in one-third of our patients and is therefore recommended as a routine procedure in connection with major liver surgery.