Tocilizumab provides dual benefits in treating immune checkpoint inhibitor-associated arthritis and preventing relapse during ICI rechallenge: the TAPIR study.

BACKGROUND: The aim of this retrospective study was to evaluate the dual efficacy of tocilizumab (TCZ) in the treatment of ICI-related arthritis (ICI-AR) and the prevention of relapses after rechallenge. PATIENTS AND METHODS: We identified 26 patients with ICI-AR. The primary objectives were to evaluate TCZ efficacy in ICI-AR treatment and as secondary prophylaxis during ICI rechallenge in 11 of them. Patients received prednisone (CS) at 0.3 mg/kg tapered at 0.05 mg/kg weekly for six weeks. TCZ was administered at a dose of 8 mg/kg Q2w. In the subgroup receiving secondary prophylaxis (rechallenge n=11), TCZ was reintroduced with the same regimen concurrently with ICI rechallenge, and without the addition of CS. A control group of patients (rechallenge n=5) was rechallenged without TCZ. Secondary endpoints included post rechallenge evaluation of ICI duration, reintroduction of CS > 0.1 mg/kg/day, ICI-RA flares, and DCR. RESULTS: The median age of the patients was 70 years. The median follow-up from ICI initiation was 864 days. Among the 20 patients treated with TCZ for ICI-AR, all (100%) achieved an ACR70 response rate, defined as greater than 70% improvement, at 10 weeks. 81% of these patients achieved steroid-free remission after 24 weeks on TCZ. The median follow-up period was 552 days in rechallenged patients. The results demonstrated a reduction in ICI-AR relapses upon ICI rechallenge in patients receiving TCZ prophylaxis as compared to patients who did not receive prophylaxis (17% vs 40%). The requirement for CS was completely abolished with prophylaxis (0% vs 20%), and the mean duration of ICI treatment was notably extended from 113 to 206 days. The 12-month post-rechallenge outcomes showed a disease control rate (DCR) of 77%. During TCZ prophylaxis, CXCL9 remained elevated, showing no decline from their levels at the onset of ICI-AR CONCLUSIONS: In addition to treating ICI-AR, TCZ demonstrated efficacy as a secondary prophylactic agent, preventing the recurrence symptoms and lengthening ICI treatment duration after ICI rechallenge.

French multicentre prospective evaluation of radiofrequency ablation in the management of haemorrhoidal disease.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of radiofrequency ablation (RFA) in the management of haemorrhoidal disease with 1 year's follow-up. METHOD: This prospective multicentre study assessed RFA (Rafaelo©) in outpatients with grade II-III haemorrhoids. RFA was performed in the operating room under locoregional or general anaesthesia. Primary endpoint was the evolution of a quality-of-life score adapted to the haemorrhoid pathology (HEMO-FISS-QoL) 3 months after surgery. Secondary endpoints were evolution of symptoms (prolapsus, bleeding, pain, itching, anal discomfort), complications, postoperative pain and medical leave. RESULTS: A total of 129 patients (69% men, median age 49 years) were operated on in 16 French centres. Median HEMO-FISS-QoL score dropped significantly from 17.4/100 to 0/100 (p < 0.0001) at 3 months. At 3 months, the rate of patients reporting bleeding (21% vs. 84%, p < 0.001), prolapse (34% vs. 91.3%, p < 0.001) and anal discomfort (0/10 vs. 5/10, p < 0.0001) decreased significantly. Median medical leave was 4 days [1-14]. Postoperative pain was 4/10, 1/10, 0/10 and 0/10 at weeks 1, 2, 3 and 4. Seven patients (5.4%) were reoperated on by haemorrhoidectomy for relapse, and three for complications. Reported complications were haemorrhage (3), dysuria (3), abscess (2), anal fissure (1), external haemorrhoidal thrombosis (10), pain requiring morphine (11). Degree of satisfaction was high (+ 5 at 3 months on a - 5/+ 5 scale). CONCLUSION: RFA is associated with an improvement in quality of life and symptoms with a good safety profile. As expected for minimally invasive surgery, postoperative pain is minor with short medical leave. CLINICAL TRIAL REGISTRATION AND DATE: Clinical trial NCT04229784 (18/01/2020).

A hot Jupiter orbiting a 2-million-year-old solar-mass T Tauri star.

Hot Jupiters are giant Jupiter-like exoplanets that orbit their host stars 100 times more closely than Jupiter orbits the Sun. These planets presumably form in the outer part of the primordial disk from which both the central star and surrounding planets are born, then migrate inwards and yet avoid falling into their host star. It is, however, unclear whether this occurs early in the lives of hot Jupiters, when they are still embedded within protoplanetary disks, or later, once multiple planets are formed and interact. Although numerous hot Jupiters have been detected around mature Sun-like stars, their existence has not yet been firmly demonstrated for young stars, whose magnetic activity is so intense that it overshadows the radial velocity signal that close-in giant planets can induce. Here we report that the radial velocities of the young star V830 Tau exhibit a sine wave of period 4.93 days and semi-amplitude 75 metres per second, detected with a false-alarm probability of less than 0.03 per cent, after filtering out the magnetic activity plaguing the spectra. We find that this signal is unrelated to the 2.741-day rotation period of V830 Tau and we attribute it to the presence of a planet of mass 0.77 times that of Jupiter, orbiting at a distance of 0.057 astronomical units from the host star. Our result demonstrates that hot Jupiters can migrate inwards in less than two million years, probably as a result of planet­disk interactions.

[Uterine rupture in a patient with a cesarean scar pregnancy]. / Cas clinique. Rupture utérine en début de grossesse sur cicatrice de césarienne.

Caesarean scar pregnancy is a rare form of ectopic pregnancy, but it is increasingly common due to the increasing number of caesarean sections and advances in medical imaging. There are two types of cesarean scar pregnancy depending on the depth of the implantation : endogenous type I and exogenous type II. In the case of a pregnancy resulting from a type II caesarean scar, the main complication is uterine rupture, which could be life-threatening for the patient. Early diagnosis and treatment are therefore essential for the woman. We report the case of a patient in early pregnancy with a history of cesarean section who presented with severe pelvic pain due to uterine rupture.

La grossesse sur cicatrice de césarienne est une forme rare de grossesse extra-utérine mais dont la fréquence augmente en raison du nombre croissant de césariennes et du progrès de l'imagerie médicale. Il en existe deux types en fonction de la profondeur d'implantation : le type I endogène et le type II exogène. Dans les cas d'une grossesse sur cicatrice de césarienne de type II, la complication principale est la rupture utérine qui pourrait engager le pronostic vital de la patiente. Un diagnostic et un traitement précoce sont donc primordiaux pour la patiente. Nous rapportons le cas d'une patiente en début de grossesse avec un antécédent de césarienne qui se présente pour des douleurs abdominales aiguës dues à une rupture utérine.

[Alcohol, pregnancy and breast-feeding]. / Alcool, grossesse et allaitement.

Perinatal studies over the last ten years report that 3 % of pregnant women have alcohol consumption. The malformative and neurological consequences of prenatal exposure to alcohol have been known for more than 50 years. Research has shown that the effects of alcohol during pregnancy and breast-feeding go far beyond visible abnormalities at birth. Neurological consequences, from minor psychomotor retardation to severe behavioural disorders, make all the severity of this intoxication and justify strict instructions to refrain from taking alcohol during pregnancy and breast-feeding.

Les enquêtes périnatales réalisées au cours des dix dernières années rapportent que 3 % des femmes enceintes consomment de l'alcool. Les conséquences malformatives et neurologiques de l'exposition prénatale à l'alcool sont pourtant connues depuis plus de 50 ans et l'avancée des recherches a montré que les effets de l'alcool durant la grossesse et l'allaitement vont bien au-delà d'anomalies visibles à la naissance. Les conséquences neurologiques, du retard mineur aux troubles comportementaux sévères, illustrent toute la gravité de cette intoxication. Ils justifient une consigne stricte d'abstention de consommation d'alcool durant la grossesse et l'allaitement.

The first joint ESGAR/ ESPR consensus statement on the technical performance of cross-sectional small bowel and colonic imaging.

OBJECTIVES: To develop guidelines describing a standardised approach to patient preparation and acquisition protocols for magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound (US) of the small bowel and colon, with an emphasis on imaging inflammatory bowel disease. METHODS: An expert consensus committee of 13 members from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and European Society of Paediatric Radiology (ESPR) undertook a six-stage modified Delphi process, including a detailed literature review, to create a series of consensus statements concerning patient preparation, imaging hardware and image acquisition protocols. RESULTS: One hundred and fifty-seven statements were scored for agreement by the panel of which 129 statements (82 %) achieved immediate consensus with a further 19 (12 %) achieving consensus after appropriate modification. Nine (6 %) statements were rejected as consensus could not be reached. CONCLUSIONS: These expert consensus recommendations can be used to help guide cross-sectional radiological practice for imaging the small bowel and colon. KEY POINTS: • Cross-sectional imaging is increasingly used to evaluate the bowel • Image quality is paramount to achieving high diagnostic accuracy • Guidelines concerning patient preparation and image acquisition protocols are provided.

[VENOUS THROMBOSIS OF THE LEFT OVARIAN AND EXTENSION TO THE RENAL VEIN]. / LE CAS CLINIQUE DU MOIS. Thrombose veineuse ovarienne gauche et extension à la veine rénale.

Ovarian vein thrombosis is a rare, but potentially serious postpartum complication. In 80% of the cases, it occurs on the right side and in less than 6% on the left side; it is bilateral in 14% of cases. The usual clinical features include abdominal pain, fever and leucocytosis. However, the diagnosis is often complicated by other non specific signs and symptoms. Ovarian vein thrombosis may cause sepsis, pulmonary thromboembolism, and thrombosis of the inferior vena cava and the renal vein. The diagnosis can be established by CT scan or nuclear magnetic resonance imaging, which has a high sensitivity and specificity. Treatment for the ovarian vein thrombosis includes antibiotics and anticoagulation. The complications can sometimes be surgically managed. Prompt diagnosis and treatment can decrease the morbidity and the mortality. Nowadays, the fatal issue is rare as the appropriate treatment is quickly instaured.

Radiofrequency ablation of metastases from osteosarcoma in patients under 25 years: the SCFE experience.

BACKGROUND: Radiofrequency ablation (RFA) has demonstrated its effectiveness in controlling metastases measuring less than 3 cm in several adult malignancies but not yet in osteosarcoma. We report our experience of RFA in the treatment of metastases in adolescents and young adults (AYA) with osteosarcoma. PROCEDURE: Sixteen patients treated for osteosarcoma in French Society of Childhood Cancer centers had undergone an RFA procedure between 2006 and 2012. RESULTS: Thirteen sessions were performed in 10 patients to treat 22 lung metastases. Seven patients were in complete remission at last follow up (range 19-51 months; median, 24 months after RFA). None had a recurrence at RFA sites. We report three cases each of hemoptysis and pneumothorax. Eight sessions were performed in seven patients to treat bone lesions. PROCEDURE was intended as: curative for a small metastatic lesion (n = 3, all in remission more than 3 years after); local control of small bone lesions in multi-metastatic diseases (n = 3); analgesia (n = 1). Complications included one first-degree burn, one fracture, and one soft tissue infection. CONCLUSIONS: RFA is feasible in AYA with osteosarcoma. It efficiently achieved local control of small peripheral lung metastases. Its role in the curative care of small secondary bone lesions remains to be confirmed.

Lower limbs power and stiffness after whole-body vibration.

The interest in whole-body vibration (WBV) for the enhancement of neuromuscular performance has received considerable attention. However, scientific evidence supporting the optimal prescription of WBV settings is lacking. This study investigated the acute effect of WBV combining high frequency/high peak-to-peak displacement (HH) or low frequency/low peak-to-peak displacement (LL) vs. sham intervention (SHAM) on lower limb muscle power and stiffness. A total of 223 volunteers were randomly assigned to either the HH, LL or SHAM group. Countermovement jump (CMJ) height, maximal and average power, maximal and average lower limbs stiffness obtained during a hopping test were recorded before and after the respective intervention. After the intervention, the HH group showed an increase of 4.64% in CMJ height (p<0.001) whereas the values of both the LL and SHAM groups did not change. In addition, maximal and average power of the lower limbs were significantly increased in all groups (p<0.001; 10.89% and 12.82%, respectively) while no effect on lower limbs stiffness was observed. Our data show that high frequency combined with high peak-to-peak displacement is the most optimal WBV setting for CMJ height enhancement. Further investigation should be undertaken to ascertain the effectiveness of WBV on lower limbs stiffness.

Comparison of contamination of femoral heads and pre-processed bone chips during hip revision arthroplasty.

With bone impaction grafting, cancellous bone chips made from allograft femoral heads are impacted in a bone defect, which introduces an additional source of infection. The potential benefit of the use of pre-processed bone chips was investigated by comparing the bacterial contamination of bone chips prepared intraoperatively with the bacterial contamination of pre-processed bone chips at different stages in the surgical procedure. To investigate baseline contamination of the bone grafts, specimens were collected during 88 procedures before actual use or preparation of the bone chips: in 44 procedures intraoperatively prepared chips were used (Group A) and in the other 44 procedures pre-processed bone chips were used (Group B). In 64 of these procedures (32 using locally prepared bone chips and 32 using pre-processed bone chips) specimens were also collected later in the procedure to investigate contamination after use and preparation of the bone chips. In total, 8 procedures had one or more positive specimen(s) (12.5 %). Contamination rates were not significantly different between bone chips prepared at the operating theatre and pre-processed bone chips. In conclusion, there was no difference in bacterial contamination between bone chips prepared from whole femoral heads in the operating room and pre-processed bone chips, and therefore, both types of bone allografts are comparable with respect to risk of infection.

Outbreak of adenovirus D8 in a neonatal intensive care unit involving multiple simultaneous transmission pathways.

BACKGROUND: Adenovirus (ADV) outbreaks in neonatal intensive care units (NICU) can lead to durable transmission and serious adverse outcomes. This study describes the investigation and control of an ADV-D8 outbreak in an NICU, associated with ophthalmologic equipment used during retinopathy of prematurity (ROP) screening. Cases were observed in neonates, parents and nurses. METHODS: The outbreak investigation was performed including sampling patients, parents and health care workers as well as the environment for molecular detection of ADV DNA. The investigation was also conducted in the guest house where some parents were temporary residents. A retrospective cohort study focused on neonates hospitalized during the epidemic period to assess the risk associated with ROP examination. RESULTS: Fifteen cases were identified in neonates; all but one presented with conjunctivitis. Two healthcare workers and 18 parents acquired conjunctivitis. ADV DNA was identified on the RetCam and on the freezer shared by parents. All ADV-positive samples were typed as ADV-D8. ADV infections occurred more frequently in neonates who had ROP examinations (37.8% (14/37) vs (0.9% (1/110); P<0.001) (relative risk 41.6; (5.7-305.8)). The RetCam was disinfected between two examinations using a disinfectant that was virucidal on ADV after a 30-min contact. CONCLUSION: This outbreak was significantly associated with ROP examination with a RetCam that had a disinfection protocol ill-adapted to rapid patient turnover. In addition, nosocomial transmission via the parents to neonates and parent-to-parent transmission is likely to have played a role in the dissemination of cases. No further cases were observed after the new disinfection procedure was enforced.

Effect of a high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers.

Statin use may be limited by muscle side effects. Although incompletely understood to date, their pathophysiology may involve oxidative stress and impairments of mitochondrial function and of muscle Ca(2+) homeostasis. In order to simultaneously assess these mechanisms, 24 male healthy volunteers were randomized to receive either simvastatin for 80 mg daily or placebo for 8 weeks. Blood and urine samples and a stress test were performed at baseline and at follow-up, and mitochondrial respiration and Ca(2+) spark properties were evaluated on a muscle biopsy 4 days before the second stress test. Simvastatin-treated subjects were separated according to their median creatine kinase (CK) increase. Simvastatin treatment induced a significant elevation of aspartate amino transferase (3.38±5.68 vs -1.15±4.32 UI/L, P<0.001) and CK (-24.3±99.1±189.3 vs 48.3 UI/L, P=0.01) and a trend to an elevation of isoprostanes (193±408 vs 12±53 pmol/mmol creatinine, P=0.09) with no global change in mitochondrial respiration, lactate/pyruvate ratio or Ca(2+) sparks. However, among statin-treated subjects, those with the highest CK increase displayed a significantly lower Vmax rotenone succinate and an increase in Ca(2+) spark amplitude vs both subjects with the lowest CK increase and placebo-treated subjects. Moreover, Ca(2+) spark amplitude was positively correlated with treatment-induced CK increase in the whole group (r=0.71, P=0.0045). In conclusion, this study further supports that statin induced muscular toxicity may be related to alterations in mitochondrial respiration and muscle calcium homeostasis independently of underlying disease or concomitant medication.

Value of diffusion-weighted images in differentiating mid-course responders to chemotherapy for osteosarcoma compared to the histological response: preliminary results.

BACKGROUND: Preoperative diffusion-weighted MRI (DW-MRI) has been described as an efficient method to differentiate good and poor responders to chemotherapy in osteosarcoma patients. A DW-MRI performed earlier during treatment could be helpful in monitoring chemotherapy. OBJECTIVE: To assess the accuracy of DW-MRI in evaluating response to chemotherapy in the treatment of osteosarcoma, more specifically at mid-course of treatment. MATERIALS AND METHODS: This study was carried out on a prospective series of adolescents treated for long-bone osteosarcoma. MR examinations were performed at diagnosis (MRI-1), at mid-course of chemotherapy (MRI-2), and immediately before surgery (MRI-3). A DW sequence was performed using diffusion gradients of b0 and b900. The apparent diffusion coefficients (ADC1, ADC2, ADC3, respectively), their differentials (ADC2 - ADC1 and ADC3 - ADC1), and their variation (ADC2 - ADC1/ADC1 and ADC3 - ADC1/ADC1) were calculated for each of these three time points. RESULTS: Fifteen patients were included. Patients with no increase in ADC showed a poor response to chemotherapy on their histology results. At mid-course, the three calculated values were significantly different between good and poor responders. ADC2 - ADC1 enabled us to detect, with 100% specificity, four out of seven of the poor responders. There was no significant difference in the values at MRI-3 between the two groups. CONCLUSION: DW-MRI performed both at baseline and mid-course of neoadjuvant chemotherapy is an efficient method to predict further histological response of osteosarcoma. This method could be used as an early prognostic factor to monitor preoperative chemotherapy.

Increased neuronal nitric oxide synthase dimerisation is involved in rat and human pancreatic beta cell hyperactivity in obesity.

AIMS/HYPOTHESIS: Pancreatic beta cell hyperactivity is known to occur in obesity, particularly in insulin-resistant states. Our aim was to investigate whether changes in neuronal nitric oxide synthase (nNOS) function affect beta cell compensation in two relevant models: the Zucker fa/fa rats and pancreatic islets from obese humans. METHODS: Glucose-induced insulin response was evaluated in the isolated perfused rat pancreas and in human pancreatic islets from obese individuals. Expression of nNOS (also known as NOS1) and subcellular localisation of nNOS were studied by quantitative RT-PCR, immunoblotting, immunofluorescence and electron microscopy. RESULTS: Pancreatic beta cells from Zucker fa/fa rats and obese individuals were found to be hyper-responsive to glucose. Pharmacological blockade of nNOS was unable to modify beta cell response to glucose in fa/fa rats and in islets from obese individuals, suggesting an abnormal control of insulin secretion by the enzyme. In both cases, nNOS activity in islet cell extracts remained unchanged, despite a drastic increase in nNOS protein and an enhancement in the dimer/monomer ratio, pointing to the presence of high amounts of catalytically inactive enzyme. This relative decrease in activity could be mainly related to increases in islet asymmetric dimethyl-arginine content, an endogenous inhibitor of nNOS activity. In addition, mitochondrial nNOS level was decreased, which contrasts with a strongly increased association with insulin granules. CONCLUSIONS/INTERPRETATION: Increased nNOS production and dimerisation, together with a relative decrease in catalytic activity and relocalisation, are involved in beta cell hyperactivity in insulin-resistant rats but also in human islets isolated from obese individuals.

[Vascular anomalies: information documents]. / Les anomalies vasculaires : fiches d'information.

Vascular anomalies are a complex pathological group. They are composed of hemangiomas and other vascular tumors and congenital vascular malformations: venous, lymphatic, arteriovenous and capillary malformations. The management of these anomalies is difficult and must involve an interdisciplinary approach. To help patients to understand their pathology, we have made some information documents.

[Diagnosis and management of vascular anomalies]. / Diagnostic et prise en charge des anomalies vasculaires.

Vascular anomalies are a complex pathological group. They are especially difficult to study because of confusion in the terminology used. The classification developed by the International Society for the Study of Vascular Anomalies (ISSVA) in 1996 allows using a common scientific language. There are two groups of lesions: vascular tumor and vascular malformation. The management of these anomalies is difficult and must involve an interdisciplinary approach including specialists in plastic surgery, radiology, pediatry and dermatology. We propose a simplified approach for the management of these pathologies. This approach is coming from the experience of Marseille (France) multidisciplinary team.

Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo.

In a number of experimental systems in which lymphocyte depletion was induced by apoptosis-inducing manipulations, no apoptotic morphology and ladder-type DNA fragmentation were detected among freshly isolated peripheral lymphocytes ex vivo. Here we report that one alteration that can be detected among splenocytes stimulated with lymphocyte-depleting doses of dexamethasone (DEX) in vivo is a reduced uptake of 3,3'dihexyloxacarbocyanine iodide (DiOC6[3]), a fluorochrome which incorporates into cells dependent upon their mitochondrial transmembrane potential (delta psi m). In contrast, ex vivo isolated splenocytes still lacked established signs of programmed cell death (PCD):DNA degradation into high or low molecular weight fragments, ultrastructural changes of chromatin arrangement and endoplasmatic reticulum, loss in viability, or accumulation of intracellular peroxides. Moreover, no changes in cell membrane potential could be detected. A reduced delta psi m has been observed in response to different agents inducing lymphoid cell depletion in vivo (superantigen and glucocorticoids [GC]), in mature T and B lymphocytes, as well as their precursors. DEX treatment in vivo, followed by cytofluorometric purification of viable delta psi mlow splenic T cells ex vivo, revealed that this fraction of cells is irreversibly committed to undergoing DNA fragmentation. Immediately after purification neither delta psi mlow, nor delta psi mhigh cells, exhibit detectable DNA fragmentation. However, after short-term culture (37 degrees C, 1 h) delta psi mlow cells show endonucleolysis, followed by cytolysis several hours later. Incubation of delta psi mlow cells in the presence of excess amount of the GC receptor antagonist RU38486 (which displaces DEX from the GC receptor), cytokines that inhibit DEX-induced cell death, or cycloheximide fails to prevent cytolysis. The antioxidant, N-acetylcysteine, as well as linomide, an agent that effectively inhibits DEX or superantigen-induced lymphocyte depletion in vivo, also stabilize the DiOC6(3) uptake. In contrast, the endonuclease inhibitor, aurintricarboxylic acid acts at later stages of apoptosis and only retards the transition from the viable delta psi mlow to the nonviable fraction. Altogether, these data suggest a sequence of PCD-associated events in which a reduction in delta psi m constitutes an obligate irreversible step of ongoing lymphocyte death, preceding other alterations of cellular physiology, and thus allowing for the ex vivo assessment of PCD.

Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death.

Programmed cell death (PCD) is a physiological process commonly defined by alterations in nuclear morphology (apoptosis) and/or characteristic stepwise degradation of chromosomal DNA occurring before cytolysis. However, determined characteristics of PCD such as loss in mitochondrial reductase activity or cytolysis can be induced in enucleated cells, indicating cytoplasmic PCD control. Here we report a sequential disregulation of mitochondrial function that precedes cell shrinkage and nuclear fragmentation. A first cyclosporin A-inhibitable step of ongoing PCD is characterized by a reduction of mitochondrial transmembrane potential, as determined by specific fluorochromes (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine++ + iodide; 3,3'dihexyloxacarbocyanine iodide). Cytofluorometrically purified cells with reduced mitochondrial transmembrane potential are initially incapable of oxidizing hydroethidine (HE) into ethidium. Upon short-term in vitro culture, such cells acquire the capacity of HE oxidation, thus revealing a second step of PCD marked by mitochondrial generation of reactive oxygen species (ROS). This step can be selectively inhibited by rotenone and ruthenium red yet is not affected by cyclosporin A. Finally, cells reduce their volume, a step that is delayed by radical scavengers, indicating the implication of ROS in the apoptotic process. This sequence of alterations accompanying early PCD is found in very different models of apoptosis induction: glucocorticoid-induced death of lymphocytes, activation-induced PCD of T cell hybridomas, and tumor necrosis factor-induced death of U937 cells. Transfection with the antiapoptotic protooncogene Bcl-2 simultaneously inhibits mitochondrial alterations and apoptotic cell death triggered by steroids or ceramide. In vivo injection of fluorochromes such as 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide; 3,3'dihexyloxacarbocyanine iodide; or HE allows for the detection of cells that are programmed for death but still lack nuclear DNA fragmentation. In particular, assessment of mitochondrial ROS generation provides an accurate picture of PCD-mediated lymphocyte depletion. In conclusion, alterations of mitochondrial function constitute an important feature of early PCD.

[Infrapatellar fat pad: anterior crossroads of the knee]. / Le corps adipeux infra-patellaire: carrefour antérieur du genou.

The infrapatellar fat pad or Hoffa's fat pad is a cylindrical extrasynovial collection of fat located in the infrapatellar region. Anatomical, biomechanical and imaging data show that the infrapatellar fat pad constitutes a true crossroads between patella, femur and tibia and helps in understanding if not describing regional pathology. Intrinsic lesions (with abnormal signal on MRI) such as hoffitis, anterolateral impingement, plica syndrome, post-arthroscopic changes, trauma, patellar dislocation and extrasynovial tumors are less frequent. On the other hand, extrinsic lesions are more frequent and may affect the synovium, patellar ligament, vascular structures, and bursae. Mucoid and parameniscal cysts may develop in the infrapatellar fat pad. In this article, the anatomical and imaging features of the infrapatellar fat pad will be summarized and the most common lesions will be illustrated.

Alterations in mitochondrial structure and function are early events of dexamethasone-induced thymocyte apoptosis.

In this paper we used a multiparametric approach to analyze extensively the events occurring during apoptotic cell death of thymocytes, and furthermore, we asked whether alterations in mitochondrial structure and function are occurring in early stages of apoptosis. A multiparametric quantitative analysis was performed on normal or apoptotic thymocytes emerging from a few-hour culture performed in culture medium or in the presence of dexamethasone. Simultaneous detection of light scattering properties, integrity of plasma membrane (trypan blue exclusion), chromatin condensation (AO/EB staining of entire cells or PI staining of nuclei), and DNA fragmentation (in situ nick-translation in apoptotic cells) allowed a precise analysis of the preapoptotic and apoptotic stages. Moreover a thorough study of mitochondrial transmembrane potential (delta psi m) assessed following in a time course study the uptake by apoptotic cells of the cationic lipophilic dye DiOC6(3) or the J-aggregate-forming cation JC-1, indicates that a drop in delta psi m occurs very early in thymocyte apoptosis, before DNA fragmentation. This is associated with alteration in mitochondrial structure assessed by cytofluorimetric study of NAO uptake in apoptotic cells. Finally these dramatic alterations in mitochondrial structure and function occurring in early stages of apoptosis were confirmed by confocal and electron microscopy analysis.