Small structural changes of the imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitors produce an improved safety profile.

Small molecule DGAT2 inhibitors have shown promise for the treatment of metabolic diseases in preclinical models. Herein, we report the first toxicological evaluation of imidazopyridine-based DGAT2 inhibitors and show that the arteriopathy associated with imidazopyridine 1 can be mitigated with small structural modifications, and is thus not mechanism related.

[Post-treatment sequelae after breast cancer conservative surgery]. / Séquelles thérapeutiques du sein après traitement conservateur du cancer du sein.

Thanks to the earlier detection of breast cancer, the advent of neoadjuvant therapy and the development of more effective surgical procedures reducing treatment sequelae, conservative treatment has dramatically expanded over the past 15 years. Several factors have recognized negative aesthetic consequences for breast cancer patients: being overweight, having voluminous or on the contrary, very small breasts, having a tumor located in the lower quadrant, having high breast-tumor: breast-volume ratio. Tissue injuries induced by radiotherapy and chemotherapy, such as shrinking, fibrosis or induration, maximize the deleterious impact of surgery. The results of conservative treatment also deteriorate with time: weight gain is common and may result in increased breast asymmetry. Patients undergoing conservative treatment may experience sequelae including various degrees of the following dimorphisms, all possibly responsible for minor or even major breast deformity: breast asymmetry, loss of the nipple/areola complex, scar shrinkage and skin impairment, irregular shape and position of the nipple and areola. Various sensory symptoms have also been reported following conservative treatment, with patients complaining of hypo- or dysesthesia or even suffering actual pain. Breast lymphedema is also a common incapacitating after-effect that is believed to be largely underdiagnosed in clinical practice. Finally, like mastectomy, conservative breast surgery may induce serious psychological distress in patients who suffer the loss of physical integrity, womanhood or sexual arousal. Clinicians must be aware of the radiological changes indicative of late cancer recurrence. There are four types of modifications as follows: increased breast density, architectural distortion at the surgical site and formation of scar, mammary fat necrosis, and occurrence of microcalcifications. The management of sequelae of conservative breast treatment must therefore involve a multidisciplinary approach; patients not only expect better cosmetic appearance, but also a focus on other treatment advances such as improvement of psychological and sensory outcome. The interpretation of radiological images is also an integral part of the management of these patients at significant risk of recurrence.

[Efficacy of lipomodelling for the management of sequelae of breast cancer conservative treatment]. / Efficacité du lipomodelage pour la correction des séquelles du traitement conservateur du cancer du sein.

We report a study of 42 breast cancer patients undergoing lipomodelling, or fat transfer, for sequelae of conservative treatment. Detailed clinical and radiological data of the patients have been collected. These data demonstrate the feasibility of lipomodelling: the technique is simple but requires a learning curve to avoid cytosteatonecrotic lesions; the excellent results obtained in terms of shape and softness of the breast; no surgical implant or flap reconstruction is necessary; the reliability of the procedure: there is normal fat wasting within the first months after treatment, then results stabilize as the patient maintains a healthy weight; the small number of side-effects: only rare, predominantly infectious, rapidly resolving complications are induced. In conclusion, the fat transfer approach presented here represents a considerable advance for the management of moderate sequelae of conservative breast treatment. Using this technique makes it possible to restore the shape and softness of the breast better than any other surgical procedure before, particularly for patients with mild breast deformity.

[Radiological evaluation after lipomodelling for correction of breast conservative treatment sequelae]. / Aspects radiologiques des seins traités par lipomodelage après séquelles du traitement conservateur du cancer du sein.

Breast lipomodelling has been used in our unit since 2002 to correct the sequelae of conservative treatment of cancer. Morphologically, satisfactory results have been recorded and the method is likely to develop considerably. However, the technique has also been questioned because of the possible deleterious radiological impact of injecting fat into the breast. The present work investigated the radiological aspect of conserved breast reconstructed by lipomodelling in a series of 21 patients undergoing ultrasound examination, mammography and MRI, before and after the procedure. Benign-looking microcalcifications were detected on 19% of the mammographies, small (<1cm) oily cysts and complex cysts were visible on respectively 57 and 19% of ultrasound images, whereas 47% of the MRI scans indicated cytosteatonecrotic lesions. Even though multiple events could be observed, their frequency is close to that observed following other conventional breast surgery. Besides, there is clear radiological evidence of benignity. The conclusion of the study is that images obtained after lipomodelling are satisfactory and in no way suggestive of recurrence of breast cancer. Provided that radiologists and experts are aware of this pattern, there is no impact on the radiological follow-up of the patients.

[Lipomodelling for correction of breast conservative treatment sequelae. Medicolegal aspects. Expert opinion on five problematic clinical cases]. / Lipomodelage et correction des séquelles du traitement conservateur du cancer du sein Aspects médicolégaux. Le point de vue de l'expert à partir de cinq cas cliniques délicats.

In our unit, breast cancer patients suffering mild sequelae of conservative cancer treatment receive fat transfer (lipomodelling), following a precise protocol, based on mammographic and ultrasound examinations and MRI. Available data do not seem to indicate any deleterious impact on patient outcome, notably in view of radiological images, but recurrence (or rather occurrence of new ipsilateral or contralateral cancer) is frequent. The correlation between new or recurrent breast cancer and lipomodelling is high; misinterpretations are possible and frequently arise. The present paper is a description of five complex clinical cases and a discussion of the medicolegal issues that may possibly arise; it also provides tentative expert evaluation of the cases. Clinical findings are reported and analyzed. The second step is a discussion of the radiological impact of lipomodelling, and of the problems caused by the transfer of potentially malignant cells when no preoperative diagnosis of recurrence is made; the morphological and esthetic benefits of the method are described, as well as the potential beneficial impact of fat transfer, notably associated with lower breast density and injections of fat stem cells. Our conclusion is that specialized radiologists, as well as plastic surgery and oncology experts should address the question of fat transfer in operated breast cancer patients and give their reasoned opinion about potentially litigious cases. This would help minimize or solve the conflicts between patients, doctors and experts. Establishing common ground between the different stakeholders would allow the development of the technique, as lipomodelling is, according to our experience, a tremendous advance in the treatment of sequelae from conservative breast cancer surgery.

Myopericarditis revealing adult-onset Still's disease.

We report the case of a 33 year-old man presenting with fever, arthralgias, sore throat, dyspnea and chest pain. Myopericarditis was diagnosed on the basis of electrocardiogram, echocardiography and cardiac magnetic resonance imaging (MRI). The dramatic increase in ferritinemia suggested the diagnosis of adult-onset Still's disease (AOSD), which could be established according to criteria of Yamaguchi. Rapid improvement occured under corticosteroids. Myocarditis is very rare in AOSD, pericarditis being more frequent. We report herein the first description of AOSD associated myocarditis evidenced by cardiac MRI.

[Diagnostic problems in brain abscess: 45 cases]. / L'abcès cérébral reste un problème diagnostique. A propos de 45 cas.

BACKGROUND AND PURPOSE: We analysed the difficulties encountered in the differential diagnosis between brain abscess and brain tumor and their influence on treatment and outcome. METHODS: - Forty-five adults with brain abscess operated on between 1993 and 1999 were retrospectively reviewed. We studied preoperative diagnosis, clinical, radiological, bacteriological findings, surgical procedure, primary sources of infection and outcome. RESULTS: Preoperative diagnosis was right in 55.6% (25/45), wrong in 22.2% (10/45) and doubtful in 22.2% (10/45). Diffusion-weighted MR imaging was successfully used in 4 doubtful cases to make the differential diagnosis between abscess and tumor. When the preoperative diagnosis was right, the surgical procedure was a burr-hole aspiration in 73.3% (22/25) whereas when it was wrong, an excision was performed in 60% (6/10) of the cases. Aspiration was the last diagnostic investigation in 80% (8/10) of doubtful cases. Microbacterial organisms were identified in 75.5% (34/45) of the cases and primary cause of infection in 62.2% (28/45). The outcome depended on clinical status on admission, preoperative diagnosis and surgical procedure. In four cases, diffusion-weighted MRI allowed differential diagnosis between brain abscess and tumor through calculation of the Apparent Diffusion Coefficient which is low in abscess and high in cystic tumor. CONCLUSION: The diagnosis of brain abscess remains difficult in certain patients. Correct preoperative diagnosis influences the decision on the appropriate surgical procedure and helps improve outcome.

Vertebral sarcoidosis of the spine in a football player.

Osseous involvement is common in sarcoidosis, but most cases of osseous sarcoidosis occur in the long bones of the hands and feet. Vertebral involvement in sarcoidosis is rare. A case of vertebral sarcoidosis in a 19-year-old male football player is presented. The patient had clinical, radiologic, laboratory, and pathologic findings consistent with a case of vertebral sarcoidosis. A review of the literature on sarcoid involvement of the spine is also presented. Although rare, sarcoid infiltration of the vertebrae is a recognized entity. Magnetic resonance imaging can be helpful in making the diagnosis, but biopsy is needed for confirmation.

Angiogenesis in a patient with ischemic limb induced by intramuscular injection of vascular endothelial growth factor and fibrin platform.

Direct revascularization of critical ischemia of the limb is often unsuccessful due to the anatomic extent and distribution of arterial occlusive disease, and no pharmacologic treatment has proved effective in treating this condition. Patients with ischemic limb may eventually require amputation and may develop serious morbidity and mortality. The goal of limb salvage in these patients has stimulated research into alternative treatment methods, including angiogenesis. Attempts have been made to apply growth factors directly or to encode DNA for such factors, but it is unknown whether these factors remain at the target site long enough to be effective. We report our strategy of using vascular endothelial growth factor in a fibrin network, which enables the sustained release of biologic material at the target site.

Nuclear collective flow and charged-pion emission in Ne-nucleus collisions at E/A = 800 MeV.

Triple-differential cross sections of charged pions were measured for collisions of Ne projectiles at E/A = 800 MeV with NaF, Nb, and Pb targets. The reaction plane was estimated event by event from the light-baryon momentum distribution. For heavy targets, preferential emission of charged pions away from the interaction zone towards the projectile side was observed in the transverse direction. Such a preferential emission, which is not predicted by cascade calculations, may be attributed to a stronger pion absorption by the heavier spectator remnant.

Proton-proton correlations at small relative momentum in neon-nucleus collisions at E/A=400 and 800 MeV.

Proton-proton small angle correlations have been measured in neon-nucleus collisions, using the 4 pi detector Diogene, at 400 and 800 MeV per nucleon incident energies. Values of the size of the emitting region are obtained by comparison with the Koonin formula, taking into account the biases of the apparatus. The dependence of the density on target mass and incident energy is also analysed.

Exclusive measurements of mean pion multiplicities in 4He-nucleus reactions from 200 to 800 MeV/nucleon.

Mean multiplicities of pi+ and pi- in 4He collisions with C, Cu, and Pb at 200, 600, and 800 MeV/u, and with C and Pb at 400 MeV/u have been measured using the large solid angle detector Diogene. The independence of pion multiplicity on projectile incident energy, target mass and proton multiplicity is studied in comparison with intra-nuclear cascade predictions. The discrepancy between experimental results and theory is pointed out and discussed.

The Diogene 4 pi detector at Saturne.

Diogene, an electronic 4 pi detector, has been built and installed at the Saturne synchrotron in Saclay. The forward angular range (0 degree-6 degrees) is covered by 48 time-of-flight scintillator telescopes that provide charge identification. The trajectories of fragments emitted at larger angles are recorded in a cylindrical 0.4-m3 Pictorial Drift Chamber (PDC) surrounding the target. The PDC is inside a 1-T magnetic field; the axis of the PDC cylinder and the magnetic field are parallel to the beam. Good identification has been obtained for both positive and negative pi mesons and for hydrogen and helium isotopes. Multiplicities in relativistic nucleus-nucleus reactions up to 40 have been detected, limited mainly by the present electronics.