Early viscoelastometric guided fibrinogen replacement combined with escalation of clinical care reduces progression in postpartum haemorrhage: a comparison of outcomes from two prospective observational studies.

BACKGROUND: Viscoelastometric haemostatic assays (VHA) give rapid information on coagulation status, allowing individualised resuscitation. METHODS: This paper compares outcomes from two observational studies of postpartum haemorrhage (PPH) in the same institution, before and after practice changed from fixed ratio empirical transfusion of coagulation products with laboratory coagulation testing to VHA-guided fibrinogen replacement incorporated into an enhanced PPH care bundle. In both studies, all blood samples were taken near 1000 mL qualitative blood loss (QBL). In Study One, QBL started once PPH was identified, and resuscitation with coagulation blood products was empirical or based on laboratory tests of coagulation. In Study Two, QBL started at delivery and VHA was used to guide fibrinogen replacement if FIBTEM A5 was <12 mm (Claus fibrinogen ≤2 g/L) or to withhold coagulation products if FIBTEM A5 was >12 mm. RESULTS: Improved PPH outcomes were observed in Study Two, with rates of measured blood loss ≥2500 mL, ≥4 units red blood cell (RBC) transfusion, fresh frozen plasma transfusion and ≥8 units of any blood product transfusion all reduced (P < 0.01). Clinically significant improvements occurred in women with fibrinogen ≤2 g/L at study entry, where the proportion of women who received ≥4 units RBC transfusion fell from 67% in Study One to 0% in Study Two (P = 0.0007). CONCLUSIONS: These results suggest that use of VHA as part of an early bundle of PPH care targeting fibrinogen ≤2 g/L with fibrinogen concentrate reduces PPH progression. The greatest benefit was seen when fibrinogen levels were ≤2 g/L at first testing.

Clinical Features and Survival of Multiple Primary Melanoma: A Belgian Single Center Cohort.

INTRODUCTION: It remains unclear whether multiple primary melanoma (MPM) patients have a worse survival prognosis compared with single primary melanoma (SPM) patients. OBJECTIVES: To investigate the demographics, histological features, and survival of MPM versus SPM patients. METHODS: Cox regression analyses compared survival between SPM and MPM patients. Furthermore, demographics and histological features of the MPM cohort were compared with the SPM patients retrieved from dermatopathology files between 2000 and 2019. RESULTS: Out of 3853 melanoma patients, 95 MPM patients were retrieved: 81 with two primary melanomas (85.2%) and 14.8% with three or more. Mean Breslow of the first melanoma was 0.84 mm [minimum (min): 0 mm, maximum (max): 16 mm, standard deviation (SD) 1.77] versus 0.37 mm (second MPM) (min: 0 mm, max: 2.5 mm, SD 0.50) and 0.33 mm (third MPM) (min: 0 mm, max: 0.6 mm, SD 0.22). The mean Breslow for the second MPM was significantly higher for men than women (0.59 mm versus 0.27 mm). First and second melanoma in MPM patients developed on preexisting melanocytic nevi in 13% and 12%, respectively. In contrast with the mean age of primary melanoma in Belgium for women (58.2 years) and men (63.3 years), MPM patients developed their first melanoma earlier, at 44.8 years and 54.6 years, respectively. The mean distribution of anatomical localization of primary and secondary melanoma was highly similar in women, whereas in men a shift towards lower extremities was observed (19% versus 28%). The thicker the primary melanoma was, the sooner the second appeared. Follow-up (2-4/year) versus (1/year) yielded a mean Breslow of 0.29 mm and 0.55 mm, respectively. Cox regression analysis with time-varying covariate revealed a tendency for a worse prognosis in 5-year survival rates, but this was not statistically significant (p = 0.09). Patient phenotypes were not available on the histological reports. CONCLUSION: A closer follow-up regimen of MPM versus SPM patients is probably justified.

[Unilocular cutaneous lymphoma : the hand and the blade]. / Cas clinique. Le lymphome cutané uniloculaire : la main et la lame.

Mycosis fungoides (MF) is the most frequent form of cutaneous lymphomas. MF is known as the great mimicker. The tumour d'emblee form is an exceptional presentation, for which there is no precise treatment guidance. A 45-year old man presented with tumoral MF on the dorsal side of his right hand with an extension to the forefinger. After the histological, immunohistological and the TCR monoclonality proof of MF, different topical and systemic treatments have been administered. As none of these treatments provided satisfying clinical responses, a surgical excision was finally proposed, with a very good clinical outcome and no recurrence observed after 2 months. Although exceptional in the event of an MF in general, localized tumoral forms of MF could readily benefit from a surgical excision.

: Le mycosis fongoïde (MF) est le lymphome cutané le plus fréquent. Il est notamment connu pour pouvoir se manifester sous différentes formes cliniques, dont une forme tumorale d'emblée et uniloculaire, rarissime. La prise en charge spécifique de cette forme n'est pas codifiée et se base sur les mêmes principes que pour le traitement d'un MF classique. Un homme de 45 ans s'est présenté avec un MF tumoral d'emblée et uniloculaire de la face dorsale de la main droite, avec une extension vers l'index. Après confirmation du diagnostic par histologie, immunohistochimie et biologie moléculaire en 2015, il a reçu différents traitements topiques et systémiques, sans résultats probants. Devant l'échec des multiples options thérapeutiques, une excision chirurgicale a été proposée en deux temps, avec une rémission complète à 2 mois. Quoique exceptionnelle pour cette pathologie, la chirurgie reste une option devant un MF d'emblée tumoral et uni- voire pauci-loculaire, avec une excellente réponse dans ce cas-ci.

[Mucinous nevus]. / L'image du mois. Naevus mucineux.

Mucinous nevus is an exceptional entity and presents as flesh-colored to brownish papules or plaques, coalescing to form a pigmentary or verrucous lesion with either a blaschkoid, linear, grouped or zosteriform disposition. It usually appears at birth or during early childhood, but late onset has also been described. Mucinous nevus does not require additional work-up as no internal pathologies have been described. Abstention of any therapeutic intervention is usually preferred.

: Le naevus mucineux est une entité exceptionnelle, se présentant par des papules ou des plaques de couleur chair à brunâtre qui confluent sous la forme d'une lésion pigmentaire ou verruqueuse de distribution blaschkoïde, linéaire, groupée ou zostériforme. Il est le plus souvent congénital ou d'apparition précoce, mais des formes tardives ont également été rapportées. Le naevus mucineux n'est jamais associé à une pathologie interne et ne nécessite pas d'exploration complémentaire. Au vu du caractère bénin, l'abstention thérapeutique est généralement la règle.

[Monkeypox]. / Variole du singe.

Monkeypox (MPX), is a rare endemic zoonotic disease of certain areas of Central and West Africa. Nevertheless, in recent years, several outbreaks have occurred outside the African continent. Monkeypox usually presents with a flu-like prodromal period (fever, headache, chills, sweating) associated or followed by the appearance of lymphadenopathy and a typical skin rash. Transmission is suspected to be direct or indirect via contact with saliva, respiratory droplets or skin lesions of infected animals or more rarely of humans. The gold standard for diagnosis is the detection of MPX virus (MPXV) by PCR on skin lesion fluid. The evolution is usually favourable in 2 to 5 weeks but severe complications and sequelae are possible. In the absence of a specific treatment, the management is essentially supportive: appropriate local care, rehydration, analgesia and management of eventual complications.

La variole du singe (monkeypox, MPX), ou orthopoxvirose simienne, est une zoonose rare et endémique de certains pays d'Afrique Centrale et de l'Ouest. Néanmoins, ces dernières années, plusieurs épidémies sont survenues en dehors du continent africain. La MPX se manifeste, habituellement, par un prodrome pseudogrippal (fièvre, céphalées, frissons, sudations), associé ou suivi par l'apparition d'une lymphadénopathie et d'un rash typique. La transmission serait directe ou indirecte, via contact avec la salive, les gouttelettes respiratoires ou les lésions cutanées d'animaux ou, plus rarement, d'humains contaminés. Le gold standard du diagnostic est la mise en évidence du virus monkeypox (MPXV) par «polymerase chain reaction¼ (PCR) sur lésion cutanée. L'évolution est habituellement favorable en 2 à 5 semaines, mais des complications et des séquelles sévères sont possibles. En l'absence d'un traitement spécifique, le traitement de soutien comporte: soins locaux adaptés, réhydratation, antalgie et prise en charge des éventuelles complications.

A description of the coagulopathy characteristics in amniotic fluid embolism: a case report.

Amniotic fluid embolism is frequently associated with coagulopathy. However, the exact nature and evolution of the bleeding disorder is incompletely understood. We report a case of clinically diagnosed amniotic fluid embolism associated with major haemorrhage and coagulopathy. We measured sequential levels of all individual clotting factors, thrombin generation, fibrinogen, and D-dimer levels over the course of the event, beginning shortly after the patient's initial collapse and during the subsequent resuscitation, to identify the specific abnormalities of coagulation from stored blood samples. A better understanding of amniotic fluid embolism and the associated coagulopathy is an important area of research to inform targeted treatment of the coagulopathy and improve outcomes for patients.

The 2019-2020 volcanic eruption of Late'iki (Metis Shoal), Tonga.

Late'iki (previously known as Metis Shoal) is a highly active volcano in the Tofua arc with at least four temporary island-building eruptions and one submarine eruption in the last 55 years. The most recent eruption, commencing in October 2019, resulted in lava effusion and subsequent phreatic explosions, the construction of a short-lived island that was quickly eroded by wave action and possibly further phreatic activity that continued into January 2020. The two-pyroxene dacite from the 2019 eruption is similar to the 1967/8 eruptions suggesting the magma is residual from earlier eruptions and has not undergone further differentiation in the last 50 years. New observations of the 2019 eruption site confirm the lava-dominant character of the volcano summit but a thin veneer of wave-reworked, finely fragmented lava material remains that is interpreted to have been produced by phreatic explosions from hot rock-water interactions during the effusive eruption. A notable absence of quench-fragmented hyaloclastite breccias suggests that non-explosive quench fragmentation processes were minimal at these shallow depths or that hyaloclastite debris has resedimented to greater depths beyond our summit survey area.

Comparison of haematological indices and transfusion management in severe and massive postpartum haemorrhage: analysis of a two-year national prospective observational study.

INTRODUCTION: This two-year prospective cohort study compared the management of women experiencing severe or massive postpartum haemorrhage (PPH) to explore the impact of targeted blood product administration on reducing PPH progression (from >1500 mL to ≥2500 mL blood loss). During the study, viscoelastic haemostatic assays (VHA) guided blood product transfusion. METHODS: All women experiencing blood loss after PPH >1000 mL were included in a national database. Haematological indices, transfusion and PPH aetiology were analysed in severe (>1500 mL blood loss or transfusion of any blood product) and massive PPH (≥2500 mL blood loss or transfusion ≥5 units red blood cells). RESULTS: Of the 61 094 maternities in Wales (2017 to 2018), 2111 had severe and 349 massive PPH. Red blood cells were transfused to 42.5% severe and 80.6% massive PPH cases. Hypofibrinogenaemia (fibrinogen <2 g/L and/or Fibtem A5 <12 mm) was the most frequent coagulation abnormality, occurring in 5.4% severe and 17.0% massive PPH, with blood coagulation products (fresh frozen plasma, platelets, cryoprecipitate and/or fibrinogen concentrate) administered to 3.6% and 22.9%. Women with hypofibrinogenaemia received targeted fibrinogen replacement in 97.8% severe and 93.6% massive PPH. The only aetiology with similar rates of hypofibrinogenaemia in severe and massive PPH was abruption (40.0% and 36.8%). CONCLUSION: Hypofibrinogenaemia was less frequent in severe PPH, although coagulopathy was observed across a range of PPH aetiologies, highlighting the importance of coagulation testing for all. Cases of abruption in severe and massive PPH had similar rates of hypofibrinogenaemia. Early VHA-guided fibrinogen replacement may reduce PPH progression in abruption and requires further evaluation.

Introduction of standardized, cumulative quantitative measurement of blood loss into routine maternity care.

INTRODUCTION: Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity in the UK. Visual estimation of blood loss is unreliable yet remains common practice. As part of a national quality improvement project to improve care during PPH, standardized, quantitative measurement of blood loss (QBL) for all deliveries was introduced into a tertiary obstetric unit in Cardiff, Wales. METHODS: Retrospective analysis of 875 consecutive maternities between December 2017 and February 2018 was undertaken. Of these, 372 mothers had both pre- and post-partum hemoglobin (Hb) were recorded. Regression analyses were performed to investigate the relationship between change in Hb adjusted for red cell transfusion and QBL. RESULTS: The correlation coefficient between QBL and adjusted change in Hb for all deliveries (n = 372) was 0.57. This corresponded to an estimated fall of adjusted change in Hb of 15.3 g/L (95% CI: 13.1, 17.6) per 1000 mL blood loss. DISCUSSION: QBL has been shown to be reliable across all maternity settings, with reproducible results in theater and delivery rooms (on the obstetric unit and alongside midwifery-led unit). QBL is moderately correlated with adjusted change in Hb for all volumes of bleeding and gives clinicians more accurate knowledge of blood loss than visual estimation. This low-cost, low-fidelity intervention can influence the timely escalation of clinical care and therefore patient outcome.

The sensitivity and specificity of rotational thromboelastometry (ROTEM) to detect coagulopathy during moderate and severe postpartum haemorrhage: a prospective observational study.

INTRODUCTION: Point-of-care viscoelastic haemostatic assays such as rotational thromboelastometry (including ROTEM and TEG) have been used in the management of postpartum haemorrhage (PPH). This study compared results obtained from the automated ROTEM Sigma with laboratory tests of coagulation and platelet count during PPH. METHODS: A prospective observational cohort study recruited women with PPH ≥1000 mL (or clinical concern of bleeding). The Fibtem A5, Extem CT and Pltem (Extem A5 - Fibtem A5) results were compared with laboratory tests of fibrinogen, prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count. RESULTS: 521 women were recruited, including 274/277 (98.9%) of women with PPH ≥1500 mL. Fibtem A5 results were matched with laboratory fibrinogen in 552/644 (85.7%) samples. The incidence of abnormal laboratory results was low: fibrinogen ≤2 g/L 23/464 (5.0%), PT or APTT >1.5 × midpoint of reference range 4/464 (0.9%), and platelet count <75 × 109/L 11/477 (2.3%). Area-under-the-receiver operator characteristic curve for Fibtem A5 to detect fibrinogen ≤2 g/L was 0.96 (95% Confidence Interval (CI) 0.94 to 0.98, P<0.001), with sensitivity and specificity of Fibtem A5 ≤11 mm to detect fibrinogen ≤2 g/L of 0.76 and 0.96. Prolonged Extem CT results improved after treatment of hypofibrinogenaemia alone. Intervention points for platelet and fresh frozen plasma (FFP) transfusion based on ROTEM Sigma parameters could not be established. CONCLUSION: During PPH (≥1000 mL or cases of clinical concern about bleeding), ROTEM Sigma Fibtem A5 can detect fibrinogen ≤2 g/L and guide targeted fibrinogen replacement. Laboratory results should continue to be used to guide platelet and FFP transfusion.

State of the art approach to managing angina and ischemia: tailoring treatment to the evidence.

Stable angina represents a chronic and often debilitating condition that affects daily activities and quality of life in patients with chronic coronary syndromes (CCS). Current European Society of Cardiology guidelines recommend a four-step approach for the medical treatment of patients taking into consideration hemodynamic variables (heart rate and blood pressure) and the presence or absence of left ventricular dysfunction. However, CCS patients often have several comorbidities and risk factors. Thus, a tailored approach that takes into consideration patient risk factors and comorbidities may have additional benefits beyond angina relief. This is a state of the art review of stable angina treatment based on the currently available evidence.

Cardiometabolic health in premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is an increasing public health problem with a prevalence now approaching 4%. POI results in adverse effects on the skeleton and central nervous system as well as disturbances of metabolic and cardiological factors that predispose to a major increased risk of cardiovascular disease (CVD). This article reviews the effects of the premature loss of ovarian function on lipids and lipoproteins, glucose and insulin metabolism, body composition, hemostasis and blood pressure, together with effects on the development of metabolic syndrome and diabetes mellitus. The article examines the effects of POI on vascular endothelial function and inflammation that result in arterial disease, and reviews the effects of hormone replacement therapy (HRT) on these various metabolic processes and on cardiovascular outcomes. It is essential that women with POI receive hormonal treatment to help prevent the development of CVD, and that this treatment is continued at least until the normal age of menopause. It appears that HRT has a more favorable effect than the combined oral contraceptive, but larger clinical trials are needed to establish the optimal treatment. Other therapeutic measures may need to be added to correct existing metabolic abnormalities and, in particular, attention to lifestyle factors such as diet and exercise must be encouraged.

Utility of viscoelastography with TEG 6s to direct management of haemostasis during obstetric haemorrhage: a prospective observational study.

BACKGROUND: The TEG 6s is an automated cartridge-based device with limited description of use in obstetric haemorrhage. The aim of this analysis was to describe the utility of TEG 6s in identifying abnormal laboratory results of coagulation and platelet count, and inform an interventional treatment algorithm for postpartum haemorrhage. METHODS: A prospective observational cohort study of 521 women with moderate to severe obstetric haemorrhage (>1000 mL blood loss), including 372 women with at least one TEG 6s test. A non-pregnant control group was used for reference. TEG 6s test parameters Citrated Functional Fibrinogen (CFF), Citrated Kaolin TEG (CK) and Citrated Rapid TEG (CRT) were compared with paired laboratory tests of fibrinogen, PT/aPTT and platelet count, obtained during haemorrhage. RESULTS: Among 456 TEG 6s tests, 389 were matched with laboratory coagulation results. The receiver operator characteristic area-under-the-curve (95% CI) for CFF amplitude by 10 min to detect Clauss fibrinogen ≤2 g/L was 0.95 (0.91 to 0.99) (P<0.0001, sensitivity 0.74 and specificity 0.97 at ≤17 mm). False positives had median (IQR) Clauss fibrinogen of 2.4 (2.3-2.7) g/L. The CK-R time had some utility for detecting prolonged PT/aPTT, however a threshold for fresh frozen plasma transfusion was not established. A CRT maximum amplitude <57 mm, when CFF was ≥15 mm, identified four of eight samples with platelet count <75 × 109/L. CONCLUSION: The TEG 6s CFF can be used to identify low fibrinogen during obstetric haemorrhage. A value to identify transfusion thresholds for PT/aPTT and platelets was not established, and laboratory results should continue to be used.

[PD-L1 : a natural immunosuppressor related to carcinogenesis. A pathologist's point of view]. / Le PD-L1 : un immunosuppresseur naturel impliqué dans la carcinogenèse Le point de vue du pathologiste.

The goal of this article is to emphasize the role of anatomopathology for the intratumoral detection of the immune checkpoint PD-L1. This molecule is one of the main targets in the anti-cancer immunotherapy. The binding of PD-L1 to its receptor PD-1 results in the inactivation of the cytotoxic T-cells, thus providing a mechanism of keeping immune reactions under control. This process can be circumvented by tumour cells to evade immune system. By blocking PD-1/PD-L1 binding, it is possible to reactivate T-cells targeting tumour neo-antigens. This article focuses on how PD-L1 works, on its implication in neoplastic processes, on the general principles of its therapeutic blockade, on the biomarkers underlying the treatment efficacy and on the practical implications of these biomarkers, especially in the anatomopathological practice.

Le but de cet article est de démontrer le rôle de l'anatomie pathologique dans la détection intra-tumorale du checkpoint immunitaire PD-L1. Ce dernier est l'une des principales cibles de l'immunothérapie à visée oncologique. La liaison du ligand PD-L1 à son récepteur PD-1 permet d'inhiber l'action des lymphocytes T cytotoxiques et, ainsi, de garder sous contrôle les réactions immunitaires. Ce processus peut être détourné par les cellules tumorales pour échapper à l'immunosurveillance. En bloquant le couple PD-L1/PD-1, il est possible de réactiver les lymphocytes T dirigés contre les néo-antigènes tumoraux. Nous nous concentrons, dans cet article, sur le mode de fonctionnement général de PD-L1, sur son implication dans les processus néoplasiques, sur le principe de son blocage thérapeutique, sur les biomarqueurs de l'efficacité du traitement et sur l'utilisation pratique de ces biomarqueurs, particulièrement dans la pratique anatomo-pathologique.

[Melanoma : the patient's care pathway. From diagnosis to therapy]. / Le mélanome : le trajet de soins du patient. Le mélanome : le trajet de soins du patient Du diagnostic au traitement Du diagnostic au traitement.

The management of melanoma is a typical example of a pluridisciplinary approach, in order to provide the patient with a rapid and adequate treatment plan after the initial diagnosis. Both in the domains of dermatology, pathology and oncology, enormous progress has been made. Recent advances permit a rapid access to diagnostic techniques using teledermoscopy, an improved diagnostic accuracy using dermoscopy, pre-interventional high-frequency ultrasound and optical coherence tomography, a determination of risk factors using immunohistochemistry and genetic analyses on the pathology samples. Furthermore, the development of immunotherapies, in particular the anti-PD1 antibodies, and the directed therapies, therapies permitting an increased number of patients to experience an increased survival with an acceptable tolerance profile in the event of metastatic lesions. This article describes the patient's care pathway, from the initial diagnosis, staging, to an eventual treatment and follow-up.

Le traitement du mélanome est un exemple type de collaboration multidisciplinaire, afin de pouvoir garantir au patient une prise en charge rapide dès le moment de la détection de la lésion. Tant au niveau dermatologique, anatomopathologique et oncologique, d'énormes progrès ont eu lieu ces dernières années. Ils permettent un accès au diagnostic de plus en rapide par la télédermoscopie, une précision diagnostique accrue par la dermoscopie, l'ultrason à haute fréquence et la tomographie par cohérence optique, une détermination des facteurs de risque immunohistochimiques et génétiques sur les analyses anatomo-pathologiques ainsi que le recours à des immunothérapies, notamment les anti-PD1, et à des traitements ciblés. Ces nouveaux traitements permettent souvent une plus longue survie du patient, avec un profil de tolérance acceptable en cas de lésions métastatiques. Cet article reprend le trajet de soins du patient, du diagnostic initial et du staging au traitement éventuel avec son suivi.

The incidence, aetiology, and coagulation management of massive postpartum haemorrhage: a two-year national prospective cohort study.

INTRODUCTION: Between 2017 and 2018 a national quality improvement initiative was introduced incorporating point-of-care viscoelastic haemostatic assays (VHA) to guide blood product transfusion. Laboratory coagulation profiles, use and results of VHA, and administration of blood products were investigated. METHODS: A two-year prospective cohort study of maternal outcomes of women experiencing massive postpartum haemorrhage (PPH) >1000 mL in Wales. In this study, cases of massive PPH (≥2500 mL and/or ≥5 units red blood cell (RBC) transfusion) were identified. RESULTS: Massive PPH occurred in 349 of 60 914 maternities (rate 5.7 per 1000). There were no deaths from PPH. Intensive care unit admission and/or hysterectomy occurred in 34/311 (10.9%) and 16/347 (4.6%), respectively. The leading cause of massive PPH was genital tract trauma (107/349, 30.6%). Two hundred and seventy-nine (80.6%) required RBC transfusion and 79/345 (22.9%) received at least one blood coagulation product. Results of VHA were recorded in 245/349 (70.2%), with 44/98 (44.9%) women tested in the first six months vs 63/77 (81.8%) in the final six months. Hypofibrinogenaemia (Clauss fibrinogen <2 g/L or FIBTEM A5 <12 mm) was observed in 56/328 (17.1%) of women, thrombocytopaenia (count <75 × 109/L) in 17/334 (5.1%) and either PT or aPTT >1.5×reference range in 10/293 (3.4%). CONCLUSION: In Wales, the use of VHA in cases of massive PPH increased over time, enabling clinicians to adopt a targeted, patient-specific approach to blood product administration, with only 22.9% of women receiving blood coagulation products and 17.1% having a documented clotting abnormality.

[Management of mycosis fungoide : focus on brentuximab vedotin]. / Comment je traite le mycosis fongoïde : à propos du brentuximab védotine, une nouvelle arme thérapeutique.

Recently, brentuximab vedotin (BV) (Adcetris®) obtained the reimbursement in Belgium for the treatment of the primary cutaneous NKT-cell lymphomas mycosis fungoides (MF), large cell anaplastic lymphoma and lymphomatoid papulosis type A. BV is a monoclonal antibody directed against the CD30 expressed on tumoral T cells. The inhibition of this pathway releases the process of apoptosis leading to the cell death of the tumoral cells. BV is reimbursed after the use of another systemic treatment without success and if the number of CD30 positive atypical T-cells is larger than 10 %. BV is administered intravenously every 3 weeks with a dosing of 1,8 mg/kg with a maximum of 16 courses. The response rates exceed 75 %. In some instances, interesting treatment responses have been observed with BV in CD30 negative patients. The principal adverse effects are neutropenia and peripheral neuropathy. Two patients are presented with longstanding multi-resistant MF that were successfully treated with BV.

Récemment, le brentuximab védotine (BV) (Adcetris®) a obtenu le remboursement en Belgique pour le traitement du lymphome cutané primitif de type mycosis fongoïde (MF), du lymphome anaplasique à larges cellules et de la papulose lymphomatoïde de type A. Le BV est un anticorps monoclonal dirigé contre le CD30 exprimé par les cellules T tumorales. L'inhibition de cette voie de signalisation induit un processus d'apoptose et conduit à la mort cellulaire. Le BV est remboursé après l'échec d'un autre traitement systémique et lorsque le nombre de cellules T atypiques exprimant le CD30 en immunohistochimie excède 10 % de la population totale sur une biopsie cutanée. Le BV est administré par voie intraveineuse toutes les 3 semaines à la posologie de 1,8 mg/kg, avec un maximum de 16 cures. Les taux de réponse globale excèdent 75 %. Certains patients négatifs pour le CD30 ont également montré une réponse thérapeutique intéressante. Les principaux effets indésirables du BV sont la neutropénie et la neuropathie périphérique. Les cas de deux patients avec un MF de longue date et multi-résistant, ayant répondu favorablement au BV, sont présentés dans cet article.

Effects of Chlorpyrifos Over Reproductive Traits of Three Sympatric Freshwater Crustaceans.

The exposure to environmentally relevant chlorpyrifos concentrations (0.03, 0.06 and 0.12 µg chlorpyrifos L-1) causes increases in precopulatory guardian behavior time, amplexus reformulation after exposure and in the number of ovigerous females in the amphipod Hyalella curvispina. Effects in incubation period, effective hatching and median lethal concentration on the decapods Macrobrachium borellii and Aegla uruguayana, both in adults and embryos, were achieved at higher concentrations than those found in the environment. Environmentally relevant chlorpyrifos concentrations appear not to affect decapods but several effects in reproductive traits of amphipods were observed.

Co-infection status of novel parvovirus's (PPV2 to 4) with porcine circovirus 2 in porcine respiratory disease complex and porcine circovirus-associated disease from 1997 to 2012.

As global pig health diseases, porcine respiratory disease complex (PRDC) and porcine circovirus-associated disease (PCVAD) generate substantial economic losses despite pigs been vaccinated against the primary causative virus, highlighting the importance of understanding virome interactions and specifically co-factor infections. Established primary endemic pathogens for PRDC include porcine circovirus 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSv) and swine influenza virus (SIV), and PCV2 aetiology in interaction with other co-infecting viruses can result in PCVAD. Porcine parvovirus (PPV) 1 is a well-characterized virus with an available vaccine preventing reproductive failure in sows. However, whilst novel PPV 2 to 7 viruses have been identified since 2001, their viral pathogenic potential in clinical and subclinical disease remains to be determined. Therefore, this study has sought to develop a better understanding of their potential role as associated co-infections in PRDC and PCVAD by examining archival samples for the presence of PCV2 and the novel parvoviruses PPV2-4 from clinically diseased pigs across production age stages. Epidemiologically, the novel PPV2 was found to be the most prevalent within the fattener age group with PPV2-4 statistically associated with pig respiratory disease and enteric ulcers. Additionally, statistical modelling by latent class analysis (LCA) on veterinary pathology scored pigs found a clustering co-factor association between PPV2 and PCV2, suggesting the novel PPV may be involved in PRDC and PCVAD. Phylogenetic analysis of novel PPVs revealed the PPV2 capsid evolution to be diverged from the original strains with a low nucleotide homology of 88%-96% between two distinct clades. These findings determine that novel PPV 2-4 viruses are statistically associated as co-infectors in a diseased pig population, and significantly detected PPV2 clustering co-infection frequency with PCV2 in PRDC and PCVAD diseased pigs through LCA analysis.